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FDA Recommends Steps to Mitigate Duodenoscope Infection Risk
Addressing recent outbreaks of serious, sometimes fatal infections associated with duodenoscopes, the Food and Drug Administration has issued recommendations for taking extra steps to improve the reprocessing of these devices, which “may further help reduce the risk of infection transmission,” the agency said in a statement issued on Aug. 4.
The extra measures are microbiological culturing, ethylene oxide sterilization, the use of a liquid chemical sterilant processing system, and repeated high-level disinfection. “Hospitals and health care facilities that utilize duodenoscopes can, in addition to meticulously following manufacturer reprocessing instructions, take one or more of these additional steps to further reduce the risk of infection and increase the safety of these medical devices,” according to the FDA’s statement announcing the measures.
The statement acknowledges that some health care facilities will not be able to implement one or more of these steps, so “it is critical that staff responsible for reprocessing duodenoscopes have the manufacturer’s instructions readily available to promote strict adherence to the reprocessing instructions in the device labeling, understand the importance of their role in reprocessing the device, and maintain proficiency in performing these reprocessing tasks.”
And while it is not possible to completely eliminate the risk of transmitting infections, “the benefits of these devices continue to outweigh the risks in appropriately selected patients,” the statement adds.
These recommendations and the statement regarding the risk-benefit profile of these devices, used to perform endoscopic retrograde cholangiopancreatography, reflect comments of panelists at a meeting of the FDA’s s gastroenterology and urology devices panel on May 14 and 15 to address recent concerns about duodenoscopes and several outbreaks in U.S. hospitals of serious infections related to the devices.
The FDA’s statement is available here.
Any infections possibly related to duodenoscopes should be reported to the manufacturer and the FDA’s MedWatch program.
Addressing recent outbreaks of serious, sometimes fatal infections associated with duodenoscopes, the Food and Drug Administration has issued recommendations for taking extra steps to improve the reprocessing of these devices, which “may further help reduce the risk of infection transmission,” the agency said in a statement issued on Aug. 4.
The extra measures are microbiological culturing, ethylene oxide sterilization, the use of a liquid chemical sterilant processing system, and repeated high-level disinfection. “Hospitals and health care facilities that utilize duodenoscopes can, in addition to meticulously following manufacturer reprocessing instructions, take one or more of these additional steps to further reduce the risk of infection and increase the safety of these medical devices,” according to the FDA’s statement announcing the measures.
The statement acknowledges that some health care facilities will not be able to implement one or more of these steps, so “it is critical that staff responsible for reprocessing duodenoscopes have the manufacturer’s instructions readily available to promote strict adherence to the reprocessing instructions in the device labeling, understand the importance of their role in reprocessing the device, and maintain proficiency in performing these reprocessing tasks.”
And while it is not possible to completely eliminate the risk of transmitting infections, “the benefits of these devices continue to outweigh the risks in appropriately selected patients,” the statement adds.
These recommendations and the statement regarding the risk-benefit profile of these devices, used to perform endoscopic retrograde cholangiopancreatography, reflect comments of panelists at a meeting of the FDA’s s gastroenterology and urology devices panel on May 14 and 15 to address recent concerns about duodenoscopes and several outbreaks in U.S. hospitals of serious infections related to the devices.
The FDA’s statement is available here.
Any infections possibly related to duodenoscopes should be reported to the manufacturer and the FDA’s MedWatch program.
Addressing recent outbreaks of serious, sometimes fatal infections associated with duodenoscopes, the Food and Drug Administration has issued recommendations for taking extra steps to improve the reprocessing of these devices, which “may further help reduce the risk of infection transmission,” the agency said in a statement issued on Aug. 4.
The extra measures are microbiological culturing, ethylene oxide sterilization, the use of a liquid chemical sterilant processing system, and repeated high-level disinfection. “Hospitals and health care facilities that utilize duodenoscopes can, in addition to meticulously following manufacturer reprocessing instructions, take one or more of these additional steps to further reduce the risk of infection and increase the safety of these medical devices,” according to the FDA’s statement announcing the measures.
The statement acknowledges that some health care facilities will not be able to implement one or more of these steps, so “it is critical that staff responsible for reprocessing duodenoscopes have the manufacturer’s instructions readily available to promote strict adherence to the reprocessing instructions in the device labeling, understand the importance of their role in reprocessing the device, and maintain proficiency in performing these reprocessing tasks.”
And while it is not possible to completely eliminate the risk of transmitting infections, “the benefits of these devices continue to outweigh the risks in appropriately selected patients,” the statement adds.
These recommendations and the statement regarding the risk-benefit profile of these devices, used to perform endoscopic retrograde cholangiopancreatography, reflect comments of panelists at a meeting of the FDA’s s gastroenterology and urology devices panel on May 14 and 15 to address recent concerns about duodenoscopes and several outbreaks in U.S. hospitals of serious infections related to the devices.
The FDA’s statement is available here.
Any infections possibly related to duodenoscopes should be reported to the manufacturer and the FDA’s MedWatch program.
FDA recommends steps to mitigate duodenoscope infection risk
Addressing recent outbreaks of serious, sometimes fatal infections associated with duodenoscopes, the Food and Drug Administration has issued recommendations for taking extra steps to improve the reprocessing of these devices, which “may further help reduce the risk of infection transmission,” the agency said in a statement issued on Aug. 4.
The extra measures are microbiological culturing, ethylene oxide sterilization, the use of a liquid chemical sterilant processing system, and repeated high-level disinfection. “Hospitals and health care facilities that utilize duodenoscopes can, in addition to meticulously following manufacturer reprocessing instructions, take one or more of these additional steps to further reduce the risk of infection and increase the safety of these medical devices,” according to the FDA’s statement announcing the measures.
The statement acknowledges that some health care facilities will not be able to implement one or more of these steps, so “it is critical that staff responsible for reprocessing duodenoscopes have the manufacturer’s instructions readily available to promote strict adherence to the reprocessing instructions in the device labeling, understand the importance of their role in reprocessing the device, and maintain proficiency in performing these reprocessing tasks.”
And while it is not possible to completely eliminate the risk of transmitting infections, “the benefits of these devices continue to outweigh the risks in appropriately selected patients,” the statement adds.
These recommendations and the statement regarding the risk-benefit profile of these devices, used to perform endoscopic retrograde cholangiopancreatography, reflect comments of panelists at a meeting of the FDA’s s gastroenterology and urology devices panel on May 14 and 15 to address recent concerns about duodenoscopes and several outbreaks in U.S. hospitals of serious infections related to the devices.
The FDA’s statement is available here.
Any infections possibly related to duodenoscopes should be reported to the manufacturer and the FDA’s MedWatch program.
Addressing recent outbreaks of serious, sometimes fatal infections associated with duodenoscopes, the Food and Drug Administration has issued recommendations for taking extra steps to improve the reprocessing of these devices, which “may further help reduce the risk of infection transmission,” the agency said in a statement issued on Aug. 4.
The extra measures are microbiological culturing, ethylene oxide sterilization, the use of a liquid chemical sterilant processing system, and repeated high-level disinfection. “Hospitals and health care facilities that utilize duodenoscopes can, in addition to meticulously following manufacturer reprocessing instructions, take one or more of these additional steps to further reduce the risk of infection and increase the safety of these medical devices,” according to the FDA’s statement announcing the measures.
The statement acknowledges that some health care facilities will not be able to implement one or more of these steps, so “it is critical that staff responsible for reprocessing duodenoscopes have the manufacturer’s instructions readily available to promote strict adherence to the reprocessing instructions in the device labeling, understand the importance of their role in reprocessing the device, and maintain proficiency in performing these reprocessing tasks.”
And while it is not possible to completely eliminate the risk of transmitting infections, “the benefits of these devices continue to outweigh the risks in appropriately selected patients,” the statement adds.
These recommendations and the statement regarding the risk-benefit profile of these devices, used to perform endoscopic retrograde cholangiopancreatography, reflect comments of panelists at a meeting of the FDA’s s gastroenterology and urology devices panel on May 14 and 15 to address recent concerns about duodenoscopes and several outbreaks in U.S. hospitals of serious infections related to the devices.
The FDA’s statement is available here.
Any infections possibly related to duodenoscopes should be reported to the manufacturer and the FDA’s MedWatch program.
Addressing recent outbreaks of serious, sometimes fatal infections associated with duodenoscopes, the Food and Drug Administration has issued recommendations for taking extra steps to improve the reprocessing of these devices, which “may further help reduce the risk of infection transmission,” the agency said in a statement issued on Aug. 4.
The extra measures are microbiological culturing, ethylene oxide sterilization, the use of a liquid chemical sterilant processing system, and repeated high-level disinfection. “Hospitals and health care facilities that utilize duodenoscopes can, in addition to meticulously following manufacturer reprocessing instructions, take one or more of these additional steps to further reduce the risk of infection and increase the safety of these medical devices,” according to the FDA’s statement announcing the measures.
The statement acknowledges that some health care facilities will not be able to implement one or more of these steps, so “it is critical that staff responsible for reprocessing duodenoscopes have the manufacturer’s instructions readily available to promote strict adherence to the reprocessing instructions in the device labeling, understand the importance of their role in reprocessing the device, and maintain proficiency in performing these reprocessing tasks.”
And while it is not possible to completely eliminate the risk of transmitting infections, “the benefits of these devices continue to outweigh the risks in appropriately selected patients,” the statement adds.
These recommendations and the statement regarding the risk-benefit profile of these devices, used to perform endoscopic retrograde cholangiopancreatography, reflect comments of panelists at a meeting of the FDA’s s gastroenterology and urology devices panel on May 14 and 15 to address recent concerns about duodenoscopes and several outbreaks in U.S. hospitals of serious infections related to the devices.
The FDA’s statement is available here.
Any infections possibly related to duodenoscopes should be reported to the manufacturer and the FDA’s MedWatch program.
FDA Approves Azelaic Acid Foam for Rosacea
A foam formulation of azelaic acid has been approved for the topical treatment of the inflammatory papules and pustules of mild to moderate rosacea, the manufacturer announced July 31.
Azelaic acid foam, 15%, was compared with a vehicle foam, applied twice a day for 12 weeks, in two studies with a total of 1,362 people with papulopustular rosacea (mean age 50.6 years) and a mean of about 21 inflammatory papules and pustules at baseline. The success rate was defined as a score of clear or minimal with at least a two-step reduction from baseline on the Investigator’s Global Assessment scale.
At 12 weeks, the success rate in the two studies, respectively, was 32% and 43% among those treated with azelaic foam vs. 23% and 32% among controls, according to the Bayer HealthCare press release announcing the approval.
The most common adverse events associated with treatment were pain at the application site in about 6%, pruritus (2.5%), dryness (0.7%), and erythema (0.7%). Warnings in the prescribing information note that treatment has been associated with “isolated” cases of hypopigmentation and can cause eye irritation, and that the contents are flammable. Patients are instructed to avoid “fire, flame, and smoking during and immediately following application.”
Azelaic acid foam is marketed as Finacea Foam by Bayer; it is the first foam formulation of azelaic acid to be approved, and it will be available in September, according to the company. A gel formulation of azelaic acid, 15%, was approved by the FDA in 2002 for topical treatment of inflammatory papules and pustules of mild to moderate rosacea.
Serious adverse events associated with azelaic acid should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch/default.htm.
A foam formulation of azelaic acid has been approved for the topical treatment of the inflammatory papules and pustules of mild to moderate rosacea, the manufacturer announced July 31.
Azelaic acid foam, 15%, was compared with a vehicle foam, applied twice a day for 12 weeks, in two studies with a total of 1,362 people with papulopustular rosacea (mean age 50.6 years) and a mean of about 21 inflammatory papules and pustules at baseline. The success rate was defined as a score of clear or minimal with at least a two-step reduction from baseline on the Investigator’s Global Assessment scale.
At 12 weeks, the success rate in the two studies, respectively, was 32% and 43% among those treated with azelaic foam vs. 23% and 32% among controls, according to the Bayer HealthCare press release announcing the approval.
The most common adverse events associated with treatment were pain at the application site in about 6%, pruritus (2.5%), dryness (0.7%), and erythema (0.7%). Warnings in the prescribing information note that treatment has been associated with “isolated” cases of hypopigmentation and can cause eye irritation, and that the contents are flammable. Patients are instructed to avoid “fire, flame, and smoking during and immediately following application.”
Azelaic acid foam is marketed as Finacea Foam by Bayer; it is the first foam formulation of azelaic acid to be approved, and it will be available in September, according to the company. A gel formulation of azelaic acid, 15%, was approved by the FDA in 2002 for topical treatment of inflammatory papules and pustules of mild to moderate rosacea.
Serious adverse events associated with azelaic acid should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch/default.htm.
A foam formulation of azelaic acid has been approved for the topical treatment of the inflammatory papules and pustules of mild to moderate rosacea, the manufacturer announced July 31.
Azelaic acid foam, 15%, was compared with a vehicle foam, applied twice a day for 12 weeks, in two studies with a total of 1,362 people with papulopustular rosacea (mean age 50.6 years) and a mean of about 21 inflammatory papules and pustules at baseline. The success rate was defined as a score of clear or minimal with at least a two-step reduction from baseline on the Investigator’s Global Assessment scale.
At 12 weeks, the success rate in the two studies, respectively, was 32% and 43% among those treated with azelaic foam vs. 23% and 32% among controls, according to the Bayer HealthCare press release announcing the approval.
The most common adverse events associated with treatment were pain at the application site in about 6%, pruritus (2.5%), dryness (0.7%), and erythema (0.7%). Warnings in the prescribing information note that treatment has been associated with “isolated” cases of hypopigmentation and can cause eye irritation, and that the contents are flammable. Patients are instructed to avoid “fire, flame, and smoking during and immediately following application.”
Azelaic acid foam is marketed as Finacea Foam by Bayer; it is the first foam formulation of azelaic acid to be approved, and it will be available in September, according to the company. A gel formulation of azelaic acid, 15%, was approved by the FDA in 2002 for topical treatment of inflammatory papules and pustules of mild to moderate rosacea.
Serious adverse events associated with azelaic acid should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch/default.htm.
FDA approves azelaic acid foam for rosacea
A foam formulation of azelaic acid has been approved for the topical treatment of the inflammatory papules and pustules of mild to moderate rosacea, the manufacturer announced July 31.
Azelaic acid foam, 15%, was compared with a vehicle foam, applied twice a day for 12 weeks, in two studies with a total of 1,362 people with papulopustular rosacea (mean age 50.6 years) and a mean of about 21 inflammatory papules and pustules at baseline. The success rate was defined as a score of clear or minimal with at least a two-step reduction from baseline on the Investigator’s Global Assessment scale.
At 12 weeks, the success rate in the two studies, respectively, was 32% and 43% among those treated with azelaic foam vs. 23% and 32% among controls, according to the Bayer HealthCare press release announcing the approval.
The most common adverse events associated with treatment were pain at the application site in about 6%, pruritus (2.5%), dryness (0.7%), and erythema (0.7%). Warnings in the prescribing information note that treatment has been associated with “isolated” cases of hypopigmentation and can cause eye irritation, and that the contents are flammable. Patients are instructed to avoid “fire, flame, and smoking during and immediately following application.”
Azelaic acid foam is marketed as Finacea Foam by Bayer; it is the first foam formulation of azelaic acid to be approved, and it will be available in September, according to the company. A gel formulation of azelaic acid, 15%, was approved by the FDA in 2002 for topical treatment of inflammatory papules and pustules of mild to moderate rosacea.
Serious adverse events associated with azelaic acid should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch/default.htm.
A foam formulation of azelaic acid has been approved for the topical treatment of the inflammatory papules and pustules of mild to moderate rosacea, the manufacturer announced July 31.
Azelaic acid foam, 15%, was compared with a vehicle foam, applied twice a day for 12 weeks, in two studies with a total of 1,362 people with papulopustular rosacea (mean age 50.6 years) and a mean of about 21 inflammatory papules and pustules at baseline. The success rate was defined as a score of clear or minimal with at least a two-step reduction from baseline on the Investigator’s Global Assessment scale.
At 12 weeks, the success rate in the two studies, respectively, was 32% and 43% among those treated with azelaic foam vs. 23% and 32% among controls, according to the Bayer HealthCare press release announcing the approval.
The most common adverse events associated with treatment were pain at the application site in about 6%, pruritus (2.5%), dryness (0.7%), and erythema (0.7%). Warnings in the prescribing information note that treatment has been associated with “isolated” cases of hypopigmentation and can cause eye irritation, and that the contents are flammable. Patients are instructed to avoid “fire, flame, and smoking during and immediately following application.”
Azelaic acid foam is marketed as Finacea Foam by Bayer; it is the first foam formulation of azelaic acid to be approved, and it will be available in September, according to the company. A gel formulation of azelaic acid, 15%, was approved by the FDA in 2002 for topical treatment of inflammatory papules and pustules of mild to moderate rosacea.
Serious adverse events associated with azelaic acid should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch/default.htm.
A foam formulation of azelaic acid has been approved for the topical treatment of the inflammatory papules and pustules of mild to moderate rosacea, the manufacturer announced July 31.
Azelaic acid foam, 15%, was compared with a vehicle foam, applied twice a day for 12 weeks, in two studies with a total of 1,362 people with papulopustular rosacea (mean age 50.6 years) and a mean of about 21 inflammatory papules and pustules at baseline. The success rate was defined as a score of clear or minimal with at least a two-step reduction from baseline on the Investigator’s Global Assessment scale.
At 12 weeks, the success rate in the two studies, respectively, was 32% and 43% among those treated with azelaic foam vs. 23% and 32% among controls, according to the Bayer HealthCare press release announcing the approval.
The most common adverse events associated with treatment were pain at the application site in about 6%, pruritus (2.5%), dryness (0.7%), and erythema (0.7%). Warnings in the prescribing information note that treatment has been associated with “isolated” cases of hypopigmentation and can cause eye irritation, and that the contents are flammable. Patients are instructed to avoid “fire, flame, and smoking during and immediately following application.”
Azelaic acid foam is marketed as Finacea Foam by Bayer; it is the first foam formulation of azelaic acid to be approved, and it will be available in September, according to the company. A gel formulation of azelaic acid, 15%, was approved by the FDA in 2002 for topical treatment of inflammatory papules and pustules of mild to moderate rosacea.
Serious adverse events associated with azelaic acid should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch/default.htm.
FDA approves ReShape intragastric balloon device for weight loss
The first intragastric balloon–based device designed to help obese people lose weight has been approved by the Food and Drug Administration, providing a treatment option that is less invasive than bariatric surgery and gastric banding.
The FDA approved the ReShape Integrated Dual Balloon System on July 28, for “weight reduction when used in conjunction with diet and exercise, in obese patients with a body mass index (BMI) of 30 kg/m2-40 kg/m2 and one or more obesity-related comorbid conditions,” in adults who have not been able to lose weight with diet and exercise alone, according to the agency’s approval letter. Laparoscopic gastric banding is indicated for patients with a BMI of at least 40 kg/m2 (or at least 30 kg/m2 in people with one or more obesity-related comorbidities) and bariatric surgery is usually recommended for patients with a BMI of at least 40 kg/m2 (or at least 35 kg/m2 in people with at least one obesity-related comorbidity).
The ReShape device is made up of two attached balloons that are placed in the stomach through a minimally invasive endoscopic procedure, where they are filled with about 2 cups of saline and methylene blue dye, under mild sedation; the balloons are sealed with mineral oil and left in place for up to 6 months. If a balloon ruptures, the dye appears in the urine. When it is time to remove the balloons, they are deflated then removed using another endoscopic procedure.
The device was evaluated in a pivotal study at eight U.S. sites of over 300 mostly female obese patients whose mean age was about 44 years; their mean weight was about 209-213 pounds, and their mean BMI was about 35 kg/m2; 187 received the device and 139 had the endoscopy only. All participants were on a medically managed diet and exercise program. At 6 months, those in the device group had lost a mean of about 24% of their weight, vs. a mean of about 11% among controls, a statistically significant difference (P = .0041). Those who had lost weight at 6 months “maintained 60% of this weight loss through 48 weeks of follow-up,” according to the FDA.
After placement of the device, common adverse events were vomiting, nausea, and abdominal pain, but most symptoms resolved within 30 days, according to the FDA. The development of gastric ulcerations is described as the “most worrisome” device-related risk, but “there were no unanticipated adverse device effects, no deaths, no intestinal obstructions, and no gastric perforations” in the study.
Among the 265 patients who received the device (those initially enrolled in the pivotal trial plus 78 who were in the control group and opted to receive the device after the first 6 months), 20 (7.5%) experienced severe adverse events; vomiting was the most common, in 4.5%. Serious events included gastric ulcers in two patients (0.8%) at 19 and at 97 days after the device was placed; in both cases, the device was removed. Almost 15% of those who received the device had to have it removed because of an adverse event. The rate of gastric ulcers after a minor change was made to the device was 10%; and the rate of balloon deflations without migration was 6%.
The FDA summary of the approval refers to the “marginal benefit of weight loss” among those in the treatment group, compared with controls, but adds that the decision to approve the device “is based in part on the limited options available to patients with mild to moderate obesity who have failed other means for conservative weight loss.” While the effectiveness of the device is better than what would be expected with diet and exercise or pharmacologic therapy,” it is “substantially less than what would be expected with gastric banding or other surgical interventions.” The list of contraindications includes previous gastrointestinal surgery “with sequelae,” such as an obstruction or adhesions; previous bariatric surgery; any GI inflammatory disease, severe coagulopathy; and women who are pregnant or breastfeeding.
“The company plans to make the ReShape procedure available to patients first in select markets, as physicians and allied health professionals are trained in the procedure and support program to optimize patient outcome,” according to the company’s statement announcing approval.
The ReShape device has been available in Europe since 2007.
Information posted by the FDA, including labeling for professionals, is available at www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfTopic/pma/pma.cfm?num=P140012.
The first intragastric balloon–based device designed to help obese people lose weight has been approved by the Food and Drug Administration, providing a treatment option that is less invasive than bariatric surgery and gastric banding.
The FDA approved the ReShape Integrated Dual Balloon System on July 28, for “weight reduction when used in conjunction with diet and exercise, in obese patients with a body mass index (BMI) of 30 kg/m2-40 kg/m2 and one or more obesity-related comorbid conditions,” in adults who have not been able to lose weight with diet and exercise alone, according to the agency’s approval letter. Laparoscopic gastric banding is indicated for patients with a BMI of at least 40 kg/m2 (or at least 30 kg/m2 in people with one or more obesity-related comorbidities) and bariatric surgery is usually recommended for patients with a BMI of at least 40 kg/m2 (or at least 35 kg/m2 in people with at least one obesity-related comorbidity).
The ReShape device is made up of two attached balloons that are placed in the stomach through a minimally invasive endoscopic procedure, where they are filled with about 2 cups of saline and methylene blue dye, under mild sedation; the balloons are sealed with mineral oil and left in place for up to 6 months. If a balloon ruptures, the dye appears in the urine. When it is time to remove the balloons, they are deflated then removed using another endoscopic procedure.
The device was evaluated in a pivotal study at eight U.S. sites of over 300 mostly female obese patients whose mean age was about 44 years; their mean weight was about 209-213 pounds, and their mean BMI was about 35 kg/m2; 187 received the device and 139 had the endoscopy only. All participants were on a medically managed diet and exercise program. At 6 months, those in the device group had lost a mean of about 24% of their weight, vs. a mean of about 11% among controls, a statistically significant difference (P = .0041). Those who had lost weight at 6 months “maintained 60% of this weight loss through 48 weeks of follow-up,” according to the FDA.
After placement of the device, common adverse events were vomiting, nausea, and abdominal pain, but most symptoms resolved within 30 days, according to the FDA. The development of gastric ulcerations is described as the “most worrisome” device-related risk, but “there were no unanticipated adverse device effects, no deaths, no intestinal obstructions, and no gastric perforations” in the study.
Among the 265 patients who received the device (those initially enrolled in the pivotal trial plus 78 who were in the control group and opted to receive the device after the first 6 months), 20 (7.5%) experienced severe adverse events; vomiting was the most common, in 4.5%. Serious events included gastric ulcers in two patients (0.8%) at 19 and at 97 days after the device was placed; in both cases, the device was removed. Almost 15% of those who received the device had to have it removed because of an adverse event. The rate of gastric ulcers after a minor change was made to the device was 10%; and the rate of balloon deflations without migration was 6%.
The FDA summary of the approval refers to the “marginal benefit of weight loss” among those in the treatment group, compared with controls, but adds that the decision to approve the device “is based in part on the limited options available to patients with mild to moderate obesity who have failed other means for conservative weight loss.” While the effectiveness of the device is better than what would be expected with diet and exercise or pharmacologic therapy,” it is “substantially less than what would be expected with gastric banding or other surgical interventions.” The list of contraindications includes previous gastrointestinal surgery “with sequelae,” such as an obstruction or adhesions; previous bariatric surgery; any GI inflammatory disease, severe coagulopathy; and women who are pregnant or breastfeeding.
“The company plans to make the ReShape procedure available to patients first in select markets, as physicians and allied health professionals are trained in the procedure and support program to optimize patient outcome,” according to the company’s statement announcing approval.
The ReShape device has been available in Europe since 2007.
Information posted by the FDA, including labeling for professionals, is available at www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfTopic/pma/pma.cfm?num=P140012.
The first intragastric balloon–based device designed to help obese people lose weight has been approved by the Food and Drug Administration, providing a treatment option that is less invasive than bariatric surgery and gastric banding.
The FDA approved the ReShape Integrated Dual Balloon System on July 28, for “weight reduction when used in conjunction with diet and exercise, in obese patients with a body mass index (BMI) of 30 kg/m2-40 kg/m2 and one or more obesity-related comorbid conditions,” in adults who have not been able to lose weight with diet and exercise alone, according to the agency’s approval letter. Laparoscopic gastric banding is indicated for patients with a BMI of at least 40 kg/m2 (or at least 30 kg/m2 in people with one or more obesity-related comorbidities) and bariatric surgery is usually recommended for patients with a BMI of at least 40 kg/m2 (or at least 35 kg/m2 in people with at least one obesity-related comorbidity).
The ReShape device is made up of two attached balloons that are placed in the stomach through a minimally invasive endoscopic procedure, where they are filled with about 2 cups of saline and methylene blue dye, under mild sedation; the balloons are sealed with mineral oil and left in place for up to 6 months. If a balloon ruptures, the dye appears in the urine. When it is time to remove the balloons, they are deflated then removed using another endoscopic procedure.
The device was evaluated in a pivotal study at eight U.S. sites of over 300 mostly female obese patients whose mean age was about 44 years; their mean weight was about 209-213 pounds, and their mean BMI was about 35 kg/m2; 187 received the device and 139 had the endoscopy only. All participants were on a medically managed diet and exercise program. At 6 months, those in the device group had lost a mean of about 24% of their weight, vs. a mean of about 11% among controls, a statistically significant difference (P = .0041). Those who had lost weight at 6 months “maintained 60% of this weight loss through 48 weeks of follow-up,” according to the FDA.
After placement of the device, common adverse events were vomiting, nausea, and abdominal pain, but most symptoms resolved within 30 days, according to the FDA. The development of gastric ulcerations is described as the “most worrisome” device-related risk, but “there were no unanticipated adverse device effects, no deaths, no intestinal obstructions, and no gastric perforations” in the study.
Among the 265 patients who received the device (those initially enrolled in the pivotal trial plus 78 who were in the control group and opted to receive the device after the first 6 months), 20 (7.5%) experienced severe adverse events; vomiting was the most common, in 4.5%. Serious events included gastric ulcers in two patients (0.8%) at 19 and at 97 days after the device was placed; in both cases, the device was removed. Almost 15% of those who received the device had to have it removed because of an adverse event. The rate of gastric ulcers after a minor change was made to the device was 10%; and the rate of balloon deflations without migration was 6%.
The FDA summary of the approval refers to the “marginal benefit of weight loss” among those in the treatment group, compared with controls, but adds that the decision to approve the device “is based in part on the limited options available to patients with mild to moderate obesity who have failed other means for conservative weight loss.” While the effectiveness of the device is better than what would be expected with diet and exercise or pharmacologic therapy,” it is “substantially less than what would be expected with gastric banding or other surgical interventions.” The list of contraindications includes previous gastrointestinal surgery “with sequelae,” such as an obstruction or adhesions; previous bariatric surgery; any GI inflammatory disease, severe coagulopathy; and women who are pregnant or breastfeeding.
“The company plans to make the ReShape procedure available to patients first in select markets, as physicians and allied health professionals are trained in the procedure and support program to optimize patient outcome,” according to the company’s statement announcing approval.
The ReShape device has been available in Europe since 2007.
Information posted by the FDA, including labeling for professionals, is available at www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfTopic/pma/pma.cfm?num=P140012.
FDA Approves Alirocumab, First Injectable Lipid-lowering Biologic Therapy
The Food and Drug Administration has approved the PCSK9 inhibitor alirocumab as a treatment for hypercholesterolemia, making this the first drug in this class – and the first injectable, biologic lipid-lowering therapy – to be approved in the United States.
Reflecting the votes and comments of an FDA advisory panel at a June 9 meeting, the FDA approved alirocumab for a narrower indication than that proposed by the manufacturers. The approved indication is an adjunct “to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia [HeFH] or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL-cholesterol.”
It will be marketed as Praluent, by Sanofi-Aventis US and Regeneron Pharmaceuticals. The company said the wholesale acquisition cost is $40/day, or $14,600/year.
“Praluent provides another treatment option for patients with HeFH or with known cardiovascular disease who have not been able to lower their LDL cholesterol enough on statins,” Dr. John Jenkins, director of the Office of New Drugs, Center for Drug Evaluation and Research, said in the FDA statement announcing the approval. Like evolocumab, another PCSK9 inhibitor under FDA review, alirocumab is a human monoclonal antibody that binds to PCSK9 (proprotein convertase subtilisin kexin type 9), a serine protease that reduces the number of receptors on the liver that remove LDL cholesterol from the blood. “By blocking PCSK9’s ability to work, more receptors are available to get rid of LDL cholesterol from the blood and, as a result, lower LDL cholesterol levels,” the FDA statement said.
In five placebo-controlled studies of people with HeFH or who were otherwise at high risk for myocardial infarction or stroke and were taking maximally tolerated doses of a statin, with or without other lipid‑modifying therapies, LDL cholesterol was reduced by 36% to 59%, compared with placebo, according to the FDA statement. In these studies, almost 2,500 individuals were treated with alirocumab. The most common adverse events associated with alirocumab included itching, swelling, pain, or bruising at the injection site, and nasopharyngitis. Hypersensitivity vasculitis (and hypersensitivity reactions requiring hospitalization have also been reported, according to the statement.
The prescribing information includes a “Limitations of Use” statement that says that the effect of alirocumab “on cardiovascular morbidity and mortality has not been determined.”
Noting that many clinical trials have shown that statins reduce the risk of MI or stroke, the FDA’s statement refers to the ongoing cardiovascular outcomes study evaluating the effects of adding alirocumab to statins on cardiovascular risk. That study – the ODYSSEY Outcomes trial – is randomizing patients with recent acute coronary syndrome who are on high-intensity statin treatment to alirocumab or placebo and is evaluating a major adverse cardiovascular event endpoint, a composite of death from coronary heart disease, nonfatal MI, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization.
In a statement released by the American College of Cardiology shortly after the announcement, ACC president Kim Allan Williams Sr., said that “the ACC eagerly awaits the results of the clinical trials that are in progress.” Until the CV outcomes data become available, expected in 2017, “we continue to recommend physicians limit prescribing to the very high risk, hard-to-treat groups approved by the FDA and otherwise follow the current guidelines, which recommend lifestyle change and, if needed, statins for most patients with or at risk of heart disease,” he added. In addition to being president of the ACC, Dr. Williams is chief of cardiology at Rush University Medical Center in Chicago. He has no relationships with industry.
The proposed indication for approval was for treating adults with primary hypercholesterolemia (nonfamilial and heterozygous familial) or mixed dyslipidemia, including patients with type 2 diabetes – either in combination with a statin or as monotherapy, including in patients who cannot tolerate statins. At a meeting on June 9, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13-3 that the manufacturer sufficiently established that the LDL cholesterol–lowering benefit of alirocumab exceeds its risks, and supported approval in some patient populations, such as those with HeFH; there was also some support for statin-intolerant patients and patients who cannot get to goal on statin therapy alone and are at a high cardiovascular risk, but not for others, such as those with mixed dyslipidemia.
On July 24, Regeneron and Sanofi-Aventis announced that the European Medicine Agency’s Committee for Medicinal Products for Human Use had recommended that alirocumab be approved in Europe for treating “certain adult patients with hypercholesterolemia.”
The FDA is expected to announce the decision on evolocumab by Aug. 27. Evolocumab’s proposed indication includes patients aged 12 years and older and adults with homozygous FH (HoFH).
The prescribing information is available at http://1.usa.gov/1KpIU82.
The Food and Drug Administration has approved the PCSK9 inhibitor alirocumab as a treatment for hypercholesterolemia, making this the first drug in this class – and the first injectable, biologic lipid-lowering therapy – to be approved in the United States.
Reflecting the votes and comments of an FDA advisory panel at a June 9 meeting, the FDA approved alirocumab for a narrower indication than that proposed by the manufacturers. The approved indication is an adjunct “to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia [HeFH] or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL-cholesterol.”
It will be marketed as Praluent, by Sanofi-Aventis US and Regeneron Pharmaceuticals. The company said the wholesale acquisition cost is $40/day, or $14,600/year.
“Praluent provides another treatment option for patients with HeFH or with known cardiovascular disease who have not been able to lower their LDL cholesterol enough on statins,” Dr. John Jenkins, director of the Office of New Drugs, Center for Drug Evaluation and Research, said in the FDA statement announcing the approval. Like evolocumab, another PCSK9 inhibitor under FDA review, alirocumab is a human monoclonal antibody that binds to PCSK9 (proprotein convertase subtilisin kexin type 9), a serine protease that reduces the number of receptors on the liver that remove LDL cholesterol from the blood. “By blocking PCSK9’s ability to work, more receptors are available to get rid of LDL cholesterol from the blood and, as a result, lower LDL cholesterol levels,” the FDA statement said.
In five placebo-controlled studies of people with HeFH or who were otherwise at high risk for myocardial infarction or stroke and were taking maximally tolerated doses of a statin, with or without other lipid‑modifying therapies, LDL cholesterol was reduced by 36% to 59%, compared with placebo, according to the FDA statement. In these studies, almost 2,500 individuals were treated with alirocumab. The most common adverse events associated with alirocumab included itching, swelling, pain, or bruising at the injection site, and nasopharyngitis. Hypersensitivity vasculitis (and hypersensitivity reactions requiring hospitalization have also been reported, according to the statement.
The prescribing information includes a “Limitations of Use” statement that says that the effect of alirocumab “on cardiovascular morbidity and mortality has not been determined.”
Noting that many clinical trials have shown that statins reduce the risk of MI or stroke, the FDA’s statement refers to the ongoing cardiovascular outcomes study evaluating the effects of adding alirocumab to statins on cardiovascular risk. That study – the ODYSSEY Outcomes trial – is randomizing patients with recent acute coronary syndrome who are on high-intensity statin treatment to alirocumab or placebo and is evaluating a major adverse cardiovascular event endpoint, a composite of death from coronary heart disease, nonfatal MI, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization.
In a statement released by the American College of Cardiology shortly after the announcement, ACC president Kim Allan Williams Sr., said that “the ACC eagerly awaits the results of the clinical trials that are in progress.” Until the CV outcomes data become available, expected in 2017, “we continue to recommend physicians limit prescribing to the very high risk, hard-to-treat groups approved by the FDA and otherwise follow the current guidelines, which recommend lifestyle change and, if needed, statins for most patients with or at risk of heart disease,” he added. In addition to being president of the ACC, Dr. Williams is chief of cardiology at Rush University Medical Center in Chicago. He has no relationships with industry.
The proposed indication for approval was for treating adults with primary hypercholesterolemia (nonfamilial and heterozygous familial) or mixed dyslipidemia, including patients with type 2 diabetes – either in combination with a statin or as monotherapy, including in patients who cannot tolerate statins. At a meeting on June 9, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13-3 that the manufacturer sufficiently established that the LDL cholesterol–lowering benefit of alirocumab exceeds its risks, and supported approval in some patient populations, such as those with HeFH; there was also some support for statin-intolerant patients and patients who cannot get to goal on statin therapy alone and are at a high cardiovascular risk, but not for others, such as those with mixed dyslipidemia.
On July 24, Regeneron and Sanofi-Aventis announced that the European Medicine Agency’s Committee for Medicinal Products for Human Use had recommended that alirocumab be approved in Europe for treating “certain adult patients with hypercholesterolemia.”
The FDA is expected to announce the decision on evolocumab by Aug. 27. Evolocumab’s proposed indication includes patients aged 12 years and older and adults with homozygous FH (HoFH).
The prescribing information is available at http://1.usa.gov/1KpIU82.
The Food and Drug Administration has approved the PCSK9 inhibitor alirocumab as a treatment for hypercholesterolemia, making this the first drug in this class – and the first injectable, biologic lipid-lowering therapy – to be approved in the United States.
Reflecting the votes and comments of an FDA advisory panel at a June 9 meeting, the FDA approved alirocumab for a narrower indication than that proposed by the manufacturers. The approved indication is an adjunct “to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia [HeFH] or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL-cholesterol.”
It will be marketed as Praluent, by Sanofi-Aventis US and Regeneron Pharmaceuticals. The company said the wholesale acquisition cost is $40/day, or $14,600/year.
“Praluent provides another treatment option for patients with HeFH or with known cardiovascular disease who have not been able to lower their LDL cholesterol enough on statins,” Dr. John Jenkins, director of the Office of New Drugs, Center for Drug Evaluation and Research, said in the FDA statement announcing the approval. Like evolocumab, another PCSK9 inhibitor under FDA review, alirocumab is a human monoclonal antibody that binds to PCSK9 (proprotein convertase subtilisin kexin type 9), a serine protease that reduces the number of receptors on the liver that remove LDL cholesterol from the blood. “By blocking PCSK9’s ability to work, more receptors are available to get rid of LDL cholesterol from the blood and, as a result, lower LDL cholesterol levels,” the FDA statement said.
In five placebo-controlled studies of people with HeFH or who were otherwise at high risk for myocardial infarction or stroke and were taking maximally tolerated doses of a statin, with or without other lipid‑modifying therapies, LDL cholesterol was reduced by 36% to 59%, compared with placebo, according to the FDA statement. In these studies, almost 2,500 individuals were treated with alirocumab. The most common adverse events associated with alirocumab included itching, swelling, pain, or bruising at the injection site, and nasopharyngitis. Hypersensitivity vasculitis (and hypersensitivity reactions requiring hospitalization have also been reported, according to the statement.
The prescribing information includes a “Limitations of Use” statement that says that the effect of alirocumab “on cardiovascular morbidity and mortality has not been determined.”
Noting that many clinical trials have shown that statins reduce the risk of MI or stroke, the FDA’s statement refers to the ongoing cardiovascular outcomes study evaluating the effects of adding alirocumab to statins on cardiovascular risk. That study – the ODYSSEY Outcomes trial – is randomizing patients with recent acute coronary syndrome who are on high-intensity statin treatment to alirocumab or placebo and is evaluating a major adverse cardiovascular event endpoint, a composite of death from coronary heart disease, nonfatal MI, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization.
In a statement released by the American College of Cardiology shortly after the announcement, ACC president Kim Allan Williams Sr., said that “the ACC eagerly awaits the results of the clinical trials that are in progress.” Until the CV outcomes data become available, expected in 2017, “we continue to recommend physicians limit prescribing to the very high risk, hard-to-treat groups approved by the FDA and otherwise follow the current guidelines, which recommend lifestyle change and, if needed, statins for most patients with or at risk of heart disease,” he added. In addition to being president of the ACC, Dr. Williams is chief of cardiology at Rush University Medical Center in Chicago. He has no relationships with industry.
The proposed indication for approval was for treating adults with primary hypercholesterolemia (nonfamilial and heterozygous familial) or mixed dyslipidemia, including patients with type 2 diabetes – either in combination with a statin or as monotherapy, including in patients who cannot tolerate statins. At a meeting on June 9, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13-3 that the manufacturer sufficiently established that the LDL cholesterol–lowering benefit of alirocumab exceeds its risks, and supported approval in some patient populations, such as those with HeFH; there was also some support for statin-intolerant patients and patients who cannot get to goal on statin therapy alone and are at a high cardiovascular risk, but not for others, such as those with mixed dyslipidemia.
On July 24, Regeneron and Sanofi-Aventis announced that the European Medicine Agency’s Committee for Medicinal Products for Human Use had recommended that alirocumab be approved in Europe for treating “certain adult patients with hypercholesterolemia.”
The FDA is expected to announce the decision on evolocumab by Aug. 27. Evolocumab’s proposed indication includes patients aged 12 years and older and adults with homozygous FH (HoFH).
The prescribing information is available at http://1.usa.gov/1KpIU82.
FROM THE FDA
FDA approves alirocumab, first injectable lipid-lowering biologic therapy
The Food and Drug Administration has approved the PCSK9 inhibitor alirocumab as a treatment for hypercholesterolemia, making this the first drug in this class – and the first injectable, biologic lipid-lowering therapy – to be approved in the United States.
Reflecting the votes and comments of an FDA advisory panel at a June 9 meeting, the FDA approved alirocumab for a narrower indication than that proposed by the manufacturers. The approved indication is an adjunct “to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia [HeFH] or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL-cholesterol.”
It will be marketed as Praluent, by Sanofi-Aventis US and Regeneron Pharmaceuticals. The company said the wholesale acquisition cost is $40/day, or $14,600/year.
“Praluent provides another treatment option for patients with HeFH or with known cardiovascular disease who have not been able to lower their LDL cholesterol enough on statins,” Dr. John Jenkins, director of the Office of New Drugs, Center for Drug Evaluation and Research, said in the FDA statement announcing the approval. Like evolocumab, another PCSK9 inhibitor under FDA review, alirocumab is a human monoclonal antibody that binds to PCSK9 (proprotein convertase subtilisin kexin type 9), a serine protease that reduces the number of receptors on the liver that remove LDL cholesterol from the blood. “By blocking PCSK9’s ability to work, more receptors are available to get rid of LDL cholesterol from the blood and, as a result, lower LDL cholesterol levels,” the FDA statement said.
In five placebo-controlled studies of people with HeFH or who were otherwise at high risk for myocardial infarction or stroke and were taking maximally tolerated doses of a statin, with or without other lipid‑modifying therapies, LDL cholesterol was reduced by 36% to 59%, compared with placebo, according to the FDA statement. In these studies, almost 2,500 individuals were treated with alirocumab. The most common adverse events associated with alirocumab included itching, swelling, pain, or bruising at the injection site, and nasopharyngitis. Hypersensitivity vasculitis (and hypersensitivity reactions requiring hospitalization have also been reported, according to the statement.
The prescribing information includes a “Limitations of Use” statement that says that the effect of alirocumab “on cardiovascular morbidity and mortality has not been determined.”
Noting that many clinical trials have shown that statins reduce the risk of MI or stroke, the FDA’s statement refers to the ongoing cardiovascular outcomes study evaluating the effects of adding alirocumab to statins on cardiovascular risk. That study – the ODYSSEY Outcomes trial – is randomizing patients with recent acute coronary syndrome who are on high-intensity statin treatment to alirocumab or placebo and is evaluating a major adverse cardiovascular event endpoint, a composite of death from coronary heart disease, nonfatal MI, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization.
In a statement released by the American College of Cardiology shortly after the announcement, ACC president Kim Allan Williams Sr., said that “the ACC eagerly awaits the results of the clinical trials that are in progress.” Until the CV outcomes data become available, expected in 2017, “we continue to recommend physicians limit prescribing to the very high risk, hard-to-treat groups approved by the FDA and otherwise follow the current guidelines, which recommend lifestyle change and, if needed, statins for most patients with or at risk of heart disease,” he added. In addition to being president of the ACC, Dr. Williams is chief of cardiology at Rush University Medical Center in Chicago. He has no relationships with industry.
The proposed indication for approval was for treating adults with primary hypercholesterolemia (nonfamilial and heterozygous familial) or mixed dyslipidemia, including patients with type 2 diabetes – either in combination with a statin or as monotherapy, including in patients who cannot tolerate statins. At a meeting on June 9, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13-3 that the manufacturer sufficiently established that the LDL cholesterol–lowering benefit of alirocumab exceeds its risks, and supported approval in some patient populations, such as those with HeFH; there was also some support for statin-intolerant patients and patients who cannot get to goal on statin therapy alone and are at a high cardiovascular risk, but not for others, such as those with mixed dyslipidemia.
On July 24, Regeneron and Sanofi-Aventis announced that the European Medicine Agency’s Committee for Medicinal Products for Human Use had recommended that alirocumab be approved in Europe for treating “certain adult patients with hypercholesterolemia.”
The FDA is expected to announce the decision on evolocumab by Aug. 27. Evolocumab’s proposed indication includes patients aged 12 years and older and adults with homozygous FH (HoFH).
The prescribing information is available at http://1.usa.gov/1KpIU82.
The Food and Drug Administration has approved the PCSK9 inhibitor alirocumab as a treatment for hypercholesterolemia, making this the first drug in this class – and the first injectable, biologic lipid-lowering therapy – to be approved in the United States.
Reflecting the votes and comments of an FDA advisory panel at a June 9 meeting, the FDA approved alirocumab for a narrower indication than that proposed by the manufacturers. The approved indication is an adjunct “to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia [HeFH] or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL-cholesterol.”
It will be marketed as Praluent, by Sanofi-Aventis US and Regeneron Pharmaceuticals. The company said the wholesale acquisition cost is $40/day, or $14,600/year.
“Praluent provides another treatment option for patients with HeFH or with known cardiovascular disease who have not been able to lower their LDL cholesterol enough on statins,” Dr. John Jenkins, director of the Office of New Drugs, Center for Drug Evaluation and Research, said in the FDA statement announcing the approval. Like evolocumab, another PCSK9 inhibitor under FDA review, alirocumab is a human monoclonal antibody that binds to PCSK9 (proprotein convertase subtilisin kexin type 9), a serine protease that reduces the number of receptors on the liver that remove LDL cholesterol from the blood. “By blocking PCSK9’s ability to work, more receptors are available to get rid of LDL cholesterol from the blood and, as a result, lower LDL cholesterol levels,” the FDA statement said.
In five placebo-controlled studies of people with HeFH or who were otherwise at high risk for myocardial infarction or stroke and were taking maximally tolerated doses of a statin, with or without other lipid‑modifying therapies, LDL cholesterol was reduced by 36% to 59%, compared with placebo, according to the FDA statement. In these studies, almost 2,500 individuals were treated with alirocumab. The most common adverse events associated with alirocumab included itching, swelling, pain, or bruising at the injection site, and nasopharyngitis. Hypersensitivity vasculitis (and hypersensitivity reactions requiring hospitalization have also been reported, according to the statement.
The prescribing information includes a “Limitations of Use” statement that says that the effect of alirocumab “on cardiovascular morbidity and mortality has not been determined.”
Noting that many clinical trials have shown that statins reduce the risk of MI or stroke, the FDA’s statement refers to the ongoing cardiovascular outcomes study evaluating the effects of adding alirocumab to statins on cardiovascular risk. That study – the ODYSSEY Outcomes trial – is randomizing patients with recent acute coronary syndrome who are on high-intensity statin treatment to alirocumab or placebo and is evaluating a major adverse cardiovascular event endpoint, a composite of death from coronary heart disease, nonfatal MI, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization.
In a statement released by the American College of Cardiology shortly after the announcement, ACC president Kim Allan Williams Sr., said that “the ACC eagerly awaits the results of the clinical trials that are in progress.” Until the CV outcomes data become available, expected in 2017, “we continue to recommend physicians limit prescribing to the very high risk, hard-to-treat groups approved by the FDA and otherwise follow the current guidelines, which recommend lifestyle change and, if needed, statins for most patients with or at risk of heart disease,” he added. In addition to being president of the ACC, Dr. Williams is chief of cardiology at Rush University Medical Center in Chicago. He has no relationships with industry.
The proposed indication for approval was for treating adults with primary hypercholesterolemia (nonfamilial and heterozygous familial) or mixed dyslipidemia, including patients with type 2 diabetes – either in combination with a statin or as monotherapy, including in patients who cannot tolerate statins. At a meeting on June 9, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13-3 that the manufacturer sufficiently established that the LDL cholesterol–lowering benefit of alirocumab exceeds its risks, and supported approval in some patient populations, such as those with HeFH; there was also some support for statin-intolerant patients and patients who cannot get to goal on statin therapy alone and are at a high cardiovascular risk, but not for others, such as those with mixed dyslipidemia.
On July 24, Regeneron and Sanofi-Aventis announced that the European Medicine Agency’s Committee for Medicinal Products for Human Use had recommended that alirocumab be approved in Europe for treating “certain adult patients with hypercholesterolemia.”
The FDA is expected to announce the decision on evolocumab by Aug. 27. Evolocumab’s proposed indication includes patients aged 12 years and older and adults with homozygous FH (HoFH).
The prescribing information is available at http://1.usa.gov/1KpIU82.
The Food and Drug Administration has approved the PCSK9 inhibitor alirocumab as a treatment for hypercholesterolemia, making this the first drug in this class – and the first injectable, biologic lipid-lowering therapy – to be approved in the United States.
Reflecting the votes and comments of an FDA advisory panel at a June 9 meeting, the FDA approved alirocumab for a narrower indication than that proposed by the manufacturers. The approved indication is an adjunct “to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia [HeFH] or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL-cholesterol.”
It will be marketed as Praluent, by Sanofi-Aventis US and Regeneron Pharmaceuticals. The company said the wholesale acquisition cost is $40/day, or $14,600/year.
“Praluent provides another treatment option for patients with HeFH or with known cardiovascular disease who have not been able to lower their LDL cholesterol enough on statins,” Dr. John Jenkins, director of the Office of New Drugs, Center for Drug Evaluation and Research, said in the FDA statement announcing the approval. Like evolocumab, another PCSK9 inhibitor under FDA review, alirocumab is a human monoclonal antibody that binds to PCSK9 (proprotein convertase subtilisin kexin type 9), a serine protease that reduces the number of receptors on the liver that remove LDL cholesterol from the blood. “By blocking PCSK9’s ability to work, more receptors are available to get rid of LDL cholesterol from the blood and, as a result, lower LDL cholesterol levels,” the FDA statement said.
In five placebo-controlled studies of people with HeFH or who were otherwise at high risk for myocardial infarction or stroke and were taking maximally tolerated doses of a statin, with or without other lipid‑modifying therapies, LDL cholesterol was reduced by 36% to 59%, compared with placebo, according to the FDA statement. In these studies, almost 2,500 individuals were treated with alirocumab. The most common adverse events associated with alirocumab included itching, swelling, pain, or bruising at the injection site, and nasopharyngitis. Hypersensitivity vasculitis (and hypersensitivity reactions requiring hospitalization have also been reported, according to the statement.
The prescribing information includes a “Limitations of Use” statement that says that the effect of alirocumab “on cardiovascular morbidity and mortality has not been determined.”
Noting that many clinical trials have shown that statins reduce the risk of MI or stroke, the FDA’s statement refers to the ongoing cardiovascular outcomes study evaluating the effects of adding alirocumab to statins on cardiovascular risk. That study – the ODYSSEY Outcomes trial – is randomizing patients with recent acute coronary syndrome who are on high-intensity statin treatment to alirocumab or placebo and is evaluating a major adverse cardiovascular event endpoint, a composite of death from coronary heart disease, nonfatal MI, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization.
In a statement released by the American College of Cardiology shortly after the announcement, ACC president Kim Allan Williams Sr., said that “the ACC eagerly awaits the results of the clinical trials that are in progress.” Until the CV outcomes data become available, expected in 2017, “we continue to recommend physicians limit prescribing to the very high risk, hard-to-treat groups approved by the FDA and otherwise follow the current guidelines, which recommend lifestyle change and, if needed, statins for most patients with or at risk of heart disease,” he added. In addition to being president of the ACC, Dr. Williams is chief of cardiology at Rush University Medical Center in Chicago. He has no relationships with industry.
The proposed indication for approval was for treating adults with primary hypercholesterolemia (nonfamilial and heterozygous familial) or mixed dyslipidemia, including patients with type 2 diabetes – either in combination with a statin or as monotherapy, including in patients who cannot tolerate statins. At a meeting on June 9, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13-3 that the manufacturer sufficiently established that the LDL cholesterol–lowering benefit of alirocumab exceeds its risks, and supported approval in some patient populations, such as those with HeFH; there was also some support for statin-intolerant patients and patients who cannot get to goal on statin therapy alone and are at a high cardiovascular risk, but not for others, such as those with mixed dyslipidemia.
On July 24, Regeneron and Sanofi-Aventis announced that the European Medicine Agency’s Committee for Medicinal Products for Human Use had recommended that alirocumab be approved in Europe for treating “certain adult patients with hypercholesterolemia.”
The FDA is expected to announce the decision on evolocumab by Aug. 27. Evolocumab’s proposed indication includes patients aged 12 years and older and adults with homozygous FH (HoFH).
The prescribing information is available at http://1.usa.gov/1KpIU82.
FROM THE FDA
FDA approves hedgehog pathway inhibitor for locally advanced BCC
Sonidegib, a hedgehog pathway inhibitor, has been approved for treating patients with locally advanced basal cell carcinoma (BCC) that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy, the Food and Drug Administration announced on July 24. The drug is taken once a day, at a recommended dose of 200 mg on an empty stomach and will be marketed as Odomzo by Novartis Pharmaceuticals. Approval was based on a study that found the objective response rate to be 58% among patients treated with the 200-mg dose; an effect that lasted for about 2-19 months, according to the FDA.
“Our increasing understanding of molecular pathways involved in cancer has led to approvals of many oncology drugs in difficult-to-treat diseases for which few therapeutic options previously existed,” Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement. “Thanks to a better understanding of the hedgehog pathway, the FDA has now approved two drugs for the treatment of basal cell carcinoma just in the last 3 years,” he added.
The first drug to treat locally advanced and metastatic basal cell carcinoma was vismodegib, marketed as Erivedge by Genentech in 2012.
The most common adverse events associated with the 200-mg dose include muscle spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhea, decreased weight, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting, and pruritus (itching). It has also been associated “with rare reports” of rhabdomyolysis, muscle spasms, and myalgia, according to the FDA.
The prescribing information includes a boxed warning about the risk of embryo-fetal toxicity, and includes recommendations to verify that women of reproductive potential are not pregnant before starting treatment and to use effective contraception during treatment and for at least 20 months after the last dose. Men on this treatment should also be advised about “the potential risk of exposure through semen and to use condoms with a pregnant partner or a female partner of reproductive potential during treatment,” and for at least 8 months after stopping treatment.
More information on the approval is available on the FDA website at www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm455865.htm.
Exposed pregnancies should be reported to Novartis at 888-669-6682. Serious adverse events associated with sonidegib should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch.
Sonidegib, a hedgehog pathway inhibitor, has been approved for treating patients with locally advanced basal cell carcinoma (BCC) that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy, the Food and Drug Administration announced on July 24. The drug is taken once a day, at a recommended dose of 200 mg on an empty stomach and will be marketed as Odomzo by Novartis Pharmaceuticals. Approval was based on a study that found the objective response rate to be 58% among patients treated with the 200-mg dose; an effect that lasted for about 2-19 months, according to the FDA.
“Our increasing understanding of molecular pathways involved in cancer has led to approvals of many oncology drugs in difficult-to-treat diseases for which few therapeutic options previously existed,” Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement. “Thanks to a better understanding of the hedgehog pathway, the FDA has now approved two drugs for the treatment of basal cell carcinoma just in the last 3 years,” he added.
The first drug to treat locally advanced and metastatic basal cell carcinoma was vismodegib, marketed as Erivedge by Genentech in 2012.
The most common adverse events associated with the 200-mg dose include muscle spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhea, decreased weight, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting, and pruritus (itching). It has also been associated “with rare reports” of rhabdomyolysis, muscle spasms, and myalgia, according to the FDA.
The prescribing information includes a boxed warning about the risk of embryo-fetal toxicity, and includes recommendations to verify that women of reproductive potential are not pregnant before starting treatment and to use effective contraception during treatment and for at least 20 months after the last dose. Men on this treatment should also be advised about “the potential risk of exposure through semen and to use condoms with a pregnant partner or a female partner of reproductive potential during treatment,” and for at least 8 months after stopping treatment.
More information on the approval is available on the FDA website at www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm455865.htm.
Exposed pregnancies should be reported to Novartis at 888-669-6682. Serious adverse events associated with sonidegib should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch.
Sonidegib, a hedgehog pathway inhibitor, has been approved for treating patients with locally advanced basal cell carcinoma (BCC) that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy, the Food and Drug Administration announced on July 24. The drug is taken once a day, at a recommended dose of 200 mg on an empty stomach and will be marketed as Odomzo by Novartis Pharmaceuticals. Approval was based on a study that found the objective response rate to be 58% among patients treated with the 200-mg dose; an effect that lasted for about 2-19 months, according to the FDA.
“Our increasing understanding of molecular pathways involved in cancer has led to approvals of many oncology drugs in difficult-to-treat diseases for which few therapeutic options previously existed,” Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement. “Thanks to a better understanding of the hedgehog pathway, the FDA has now approved two drugs for the treatment of basal cell carcinoma just in the last 3 years,” he added.
The first drug to treat locally advanced and metastatic basal cell carcinoma was vismodegib, marketed as Erivedge by Genentech in 2012.
The most common adverse events associated with the 200-mg dose include muscle spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhea, decreased weight, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting, and pruritus (itching). It has also been associated “with rare reports” of rhabdomyolysis, muscle spasms, and myalgia, according to the FDA.
The prescribing information includes a boxed warning about the risk of embryo-fetal toxicity, and includes recommendations to verify that women of reproductive potential are not pregnant before starting treatment and to use effective contraception during treatment and for at least 20 months after the last dose. Men on this treatment should also be advised about “the potential risk of exposure through semen and to use condoms with a pregnant partner or a female partner of reproductive potential during treatment,” and for at least 8 months after stopping treatment.
More information on the approval is available on the FDA website at www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm455865.htm.
Exposed pregnancies should be reported to Novartis at 888-669-6682. Serious adverse events associated with sonidegib should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch.
FDA approves oral interferon-free treatment for genotype 4 HCV infection
The first interferon-free treatment for people with genotype 4 hepatitis C infection has been approved by the Food and Drug Administration.
On July 24, the FDA approved a combination of three antivirals – ombitasvir, paritaprevir, and ritonavir – for use with ribavirin for treating hepatitis C virus (HCV) genotype 4 infections in people without cirrhosis, according to the agency’s statement announcing the approval. The combination tablet will be marketed as Technivie, by Abbvie. Ombitasvir is an HCV NS5A inhibitor, paritaprevir is an HCV NS3/4A protease inhibitor, and ritonavir is an HCV CYP3A inhibitor.
Technivie “is the first drug that has demonstrated safety and efficacy to treat genotype 4 HCV infections without the need for coadministration of interferon,” the statement said. It is administered orally. Technivie is a fixed-dose combination of paritaprevir/ritonavir (150/100 mg) co-formulated with ombitasvir (25 mg); it is dosed once a day and should be taken with a meal. It is co-administered with weight-based RBV (1000mg or 1200mg in divided doses, twice a day), taken with food, according to the company's statement announcing approval.
The FDA statement refers to that study of 135 people with chronic HCV genotype 4 infections and no cirrhosis, treated with the three antivirals plus ribavirin once a day for 12 weeks (91 patients), or without ribavirin (44 patients) for 12 weeks. All the patients on the three-drug combination plus ribavirin achieved a sustained virologic response (SVR12) 12 weeks after stopping treatment (no HCV detected in the blood) vs. 91% of those who did not take ribavirin. Fatigue, weakness, nausea, insomnia, pruritus and other skin reactions are among the most common adverse events associated with treatment with Technivie and ribavirin, according to the FDA statement.
The statement adds that the prescribing information includes a warning that elevations of liver enzymes up to greater than five times the upper limit of normal occurred in about 1% of the patients in clinical trials, which were more common among women taking contraceptives that contain ethinyl estradiol. Before starting treatment, women should discontinue contraceptives that containing ethinyl estradiol, and “hepatic laboratory testing should be performed during the first 4 weeks of treatment, and as clinically indicated thereafter,” the FDA statement said.
The three antivirals included in Technivie, plus dasabuvir (an HCV nonnucleoside NS5B polymerase inhibitor), are copackaged in the Viekira Pak, which was approved for the treatment of HCV genotype 1 chronic HCV infection, with or without ribavirin in 2014, and is also manufactured by Abbvie.
About 2.7 million people in the United States have chronic HCV infection, according to the Centers for Disease Control and Prevention. HCV genotype 4 is one of the least common types of HCV in the United States.
*This story was updated 7/24/2015.
AGA Resource
Through the AGA Roadmap to the Future of Practice, AGA offers a Hepatitis C Clinical Service line to support high-quality patient care, which is available at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.
The recent FDA approval of Daklinza and Technivie for hepatitis C offer some additional weapons in the treatment of hepatitis C; however, their approval does not dramatically alter the treatment landscape at this point. Technivie is FDA approved for genotype 4, a small fraction of patients with hepatitis C, and does not offer much improvement over off-label use of Harvoni or Viekira Pak for genotype 4 patients. Daklinza is FDA approved in combination with sofosbuvir for 12 weeks for treatment-naive patients with genotype 3 and should also be considered for off-label use for genotype 2 patients.
While SVRs for noncirrhotic treatment-naive genotype 3 patients are high, achieving high SVRs in patients with cirrhosis requires treatment extension to 24 weeks to achieve an SVR around 90% at a cost of nearly $300,000. While this is an improvement on sofosbuvir plus ribavirin for treatment-experienced patients with cirrhosis, it nevertheless is an extremely expensive option that will likely be met with resistance from payers. It will also likely be displaced as a treatment option for genotype 2 and 3 patients when Gilead's pan-genotypic NS5A inhibitor (GS-5816) makes it to market as anticipated within the next year.
Dr. Sean Koppe is director of hepatology at the University of Illinois Hospital & Health Sciences System, Chicago. He has no conflicts of interest.
The recent FDA approval of Daklinza and Technivie for hepatitis C offer some additional weapons in the treatment of hepatitis C; however, their approval does not dramatically alter the treatment landscape at this point. Technivie is FDA approved for genotype 4, a small fraction of patients with hepatitis C, and does not offer much improvement over off-label use of Harvoni or Viekira Pak for genotype 4 patients. Daklinza is FDA approved in combination with sofosbuvir for 12 weeks for treatment-naive patients with genotype 3 and should also be considered for off-label use for genotype 2 patients.
While SVRs for noncirrhotic treatment-naive genotype 3 patients are high, achieving high SVRs in patients with cirrhosis requires treatment extension to 24 weeks to achieve an SVR around 90% at a cost of nearly $300,000. While this is an improvement on sofosbuvir plus ribavirin for treatment-experienced patients with cirrhosis, it nevertheless is an extremely expensive option that will likely be met with resistance from payers. It will also likely be displaced as a treatment option for genotype 2 and 3 patients when Gilead's pan-genotypic NS5A inhibitor (GS-5816) makes it to market as anticipated within the next year.
Dr. Sean Koppe is director of hepatology at the University of Illinois Hospital & Health Sciences System, Chicago. He has no conflicts of interest.
The recent FDA approval of Daklinza and Technivie for hepatitis C offer some additional weapons in the treatment of hepatitis C; however, their approval does not dramatically alter the treatment landscape at this point. Technivie is FDA approved for genotype 4, a small fraction of patients with hepatitis C, and does not offer much improvement over off-label use of Harvoni or Viekira Pak for genotype 4 patients. Daklinza is FDA approved in combination with sofosbuvir for 12 weeks for treatment-naive patients with genotype 3 and should also be considered for off-label use for genotype 2 patients.
While SVRs for noncirrhotic treatment-naive genotype 3 patients are high, achieving high SVRs in patients with cirrhosis requires treatment extension to 24 weeks to achieve an SVR around 90% at a cost of nearly $300,000. While this is an improvement on sofosbuvir plus ribavirin for treatment-experienced patients with cirrhosis, it nevertheless is an extremely expensive option that will likely be met with resistance from payers. It will also likely be displaced as a treatment option for genotype 2 and 3 patients when Gilead's pan-genotypic NS5A inhibitor (GS-5816) makes it to market as anticipated within the next year.
Dr. Sean Koppe is director of hepatology at the University of Illinois Hospital & Health Sciences System, Chicago. He has no conflicts of interest.
The first interferon-free treatment for people with genotype 4 hepatitis C infection has been approved by the Food and Drug Administration.
On July 24, the FDA approved a combination of three antivirals – ombitasvir, paritaprevir, and ritonavir – for use with ribavirin for treating hepatitis C virus (HCV) genotype 4 infections in people without cirrhosis, according to the agency’s statement announcing the approval. The combination tablet will be marketed as Technivie, by Abbvie. Ombitasvir is an HCV NS5A inhibitor, paritaprevir is an HCV NS3/4A protease inhibitor, and ritonavir is an HCV CYP3A inhibitor.
Technivie “is the first drug that has demonstrated safety and efficacy to treat genotype 4 HCV infections without the need for coadministration of interferon,” the statement said. It is administered orally. Technivie is a fixed-dose combination of paritaprevir/ritonavir (150/100 mg) co-formulated with ombitasvir (25 mg); it is dosed once a day and should be taken with a meal. It is co-administered with weight-based RBV (1000mg or 1200mg in divided doses, twice a day), taken with food, according to the company's statement announcing approval.
The FDA statement refers to that study of 135 people with chronic HCV genotype 4 infections and no cirrhosis, treated with the three antivirals plus ribavirin once a day for 12 weeks (91 patients), or without ribavirin (44 patients) for 12 weeks. All the patients on the three-drug combination plus ribavirin achieved a sustained virologic response (SVR12) 12 weeks after stopping treatment (no HCV detected in the blood) vs. 91% of those who did not take ribavirin. Fatigue, weakness, nausea, insomnia, pruritus and other skin reactions are among the most common adverse events associated with treatment with Technivie and ribavirin, according to the FDA statement.
The statement adds that the prescribing information includes a warning that elevations of liver enzymes up to greater than five times the upper limit of normal occurred in about 1% of the patients in clinical trials, which were more common among women taking contraceptives that contain ethinyl estradiol. Before starting treatment, women should discontinue contraceptives that containing ethinyl estradiol, and “hepatic laboratory testing should be performed during the first 4 weeks of treatment, and as clinically indicated thereafter,” the FDA statement said.
The three antivirals included in Technivie, plus dasabuvir (an HCV nonnucleoside NS5B polymerase inhibitor), are copackaged in the Viekira Pak, which was approved for the treatment of HCV genotype 1 chronic HCV infection, with or without ribavirin in 2014, and is also manufactured by Abbvie.
About 2.7 million people in the United States have chronic HCV infection, according to the Centers for Disease Control and Prevention. HCV genotype 4 is one of the least common types of HCV in the United States.
*This story was updated 7/24/2015.
AGA Resource
Through the AGA Roadmap to the Future of Practice, AGA offers a Hepatitis C Clinical Service line to support high-quality patient care, which is available at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.
The first interferon-free treatment for people with genotype 4 hepatitis C infection has been approved by the Food and Drug Administration.
On July 24, the FDA approved a combination of three antivirals – ombitasvir, paritaprevir, and ritonavir – for use with ribavirin for treating hepatitis C virus (HCV) genotype 4 infections in people without cirrhosis, according to the agency’s statement announcing the approval. The combination tablet will be marketed as Technivie, by Abbvie. Ombitasvir is an HCV NS5A inhibitor, paritaprevir is an HCV NS3/4A protease inhibitor, and ritonavir is an HCV CYP3A inhibitor.
Technivie “is the first drug that has demonstrated safety and efficacy to treat genotype 4 HCV infections without the need for coadministration of interferon,” the statement said. It is administered orally. Technivie is a fixed-dose combination of paritaprevir/ritonavir (150/100 mg) co-formulated with ombitasvir (25 mg); it is dosed once a day and should be taken with a meal. It is co-administered with weight-based RBV (1000mg or 1200mg in divided doses, twice a day), taken with food, according to the company's statement announcing approval.
The FDA statement refers to that study of 135 people with chronic HCV genotype 4 infections and no cirrhosis, treated with the three antivirals plus ribavirin once a day for 12 weeks (91 patients), or without ribavirin (44 patients) for 12 weeks. All the patients on the three-drug combination plus ribavirin achieved a sustained virologic response (SVR12) 12 weeks after stopping treatment (no HCV detected in the blood) vs. 91% of those who did not take ribavirin. Fatigue, weakness, nausea, insomnia, pruritus and other skin reactions are among the most common adverse events associated with treatment with Technivie and ribavirin, according to the FDA statement.
The statement adds that the prescribing information includes a warning that elevations of liver enzymes up to greater than five times the upper limit of normal occurred in about 1% of the patients in clinical trials, which were more common among women taking contraceptives that contain ethinyl estradiol. Before starting treatment, women should discontinue contraceptives that containing ethinyl estradiol, and “hepatic laboratory testing should be performed during the first 4 weeks of treatment, and as clinically indicated thereafter,” the FDA statement said.
The three antivirals included in Technivie, plus dasabuvir (an HCV nonnucleoside NS5B polymerase inhibitor), are copackaged in the Viekira Pak, which was approved for the treatment of HCV genotype 1 chronic HCV infection, with or without ribavirin in 2014, and is also manufactured by Abbvie.
About 2.7 million people in the United States have chronic HCV infection, according to the Centers for Disease Control and Prevention. HCV genotype 4 is one of the least common types of HCV in the United States.
*This story was updated 7/24/2015.
AGA Resource
Through the AGA Roadmap to the Future of Practice, AGA offers a Hepatitis C Clinical Service line to support high-quality patient care, which is available at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.
FDA approves oral interferon-free treatment for genotype 4 HCV infection
The first interferon-free treatment for people with genotype 4 hepatitis C infection has been approved by the Food and Drug Administration.
On July 24, the FDA approved a combination of three antivirals – ombitasvir, paritaprevir, and ritonavir – for use with ribavirin for treating hepatitis C virus (HCV) genotype 4 infections in people without cirrhosis, according to the agency’s statement announcing the approval. The combination tablet will be marketed as Technivie, by Abbvie. Ombitasvir is an HCV NS5A inhibitor, paritaprevir is an HCV NS3/4A protease inhibitor, and ritonavir is an HCV CYP3A inhibitor.
Technivie “is the first drug that has demonstrated safety and efficacy to treat genotype 4 HCV infections without the need for coadministration of interferon,” the statement said. It is administered orally. Technivie is a fixed-dose combination of paritaprevir/ritonavir (150/100 mg) co-formulated with ombitasvir (25 mg); it is dosed once a day and should be taken with a meal. It is co-administered with weight-based RBV (1000mg or 1200mg in divided doses, twice a day), taken with food, according to the company's statement announcing approval.
The FDA statement refers to that study of 135 people with chronic HCV genotype 4 infections and no cirrhosis, treated with the three antivirals plus ribavirin once a day for 12 weeks (91 patients), or without ribavirin (44 patients) for 12 weeks. All the patients on the three-drug combination plus ribavirin achieved a sustained virologic response (SVR12) 12 weeks after stopping treatment (no HCV detected in the blood) vs. 91% of those who did not take ribavirin. Fatigue, weakness, nausea, insomnia, pruritus and other skin reactions are among the most common adverse events associated with treatment with Technivie and ribavirin, according to the FDA statement.
The statement adds that the prescribing information includes a warning that elevations of liver enzymes up to greater than five times the upper limit of normal occurred in about 1% of the patients in clinical trials, which were more common among women taking contraceptives that contain ethinyl estradiol. Before starting treatment, women should discontinue contraceptives that containing ethinyl estradiol, and “hepatic laboratory testing should be performed during the first 4 weeks of treatment, and as clinically indicated thereafter,” the FDA statement said.
The three antivirals included in Technivie, plus dasabuvir (an HCV nonnucleoside NS5B polymerase inhibitor), are copackaged in the Viekira Pak, which was approved for the treatment of HCV genotype 1 chronic HCV infection, with or without ribavirin in 2014, and is also manufactured by Abbvie.
About 2.7 million people in the United States have chronic HCV infection, according to the Centers for Disease Control and Prevention. HCV genotype 4 is one of the least common types of HCV in the United States.
*This story was updated 7/24/2015.
The recent FDA approval of Daklinza and Technivie for hepatitis C offer some additional weapons in the treatment of hepatitis C; however, their approval does not dramatically alter the treatment landscape at this point. Technivie is FDA approved for genotype 4, a small fraction of patients with hepatitis C, and does not offer much improvement over off-label use of Harvoni or Viekira Pak for genotype 4 patients. Daklinza is FDA approved in combination with sofosbuvir for 12 weeks for treatment-naive patients with genotype 3 and should also be considered for off-label use for genotype 2 patients.
While SVRs for noncirrhotic treatment-naive genotype 3 patients are high, achieving high SVRs in patients with cirrhosis requires treatment extension to 24 weeks to achieve an SVR around 90% at a cost of nearly $300,000. While this is an improvement on sofosbuvir plus ribavirin for treatment-experienced patients with cirrhosis, it nevertheless is an extremely expensive option that will likely be met with resistance from payers. It will also likely be displaced as a treatment option for genotype 2 and 3 patients when Gilead's pan-genotypic NS5A inhibitor (GS-5816) makes it to market as anticipated within the next year.
Dr. Sean Koppe is director of hepatology at the University of Illinois Hospital & Health Sciences System, Chicago. He has no conflicts of interest.
The recent FDA approval of Daklinza and Technivie for hepatitis C offer some additional weapons in the treatment of hepatitis C; however, their approval does not dramatically alter the treatment landscape at this point. Technivie is FDA approved for genotype 4, a small fraction of patients with hepatitis C, and does not offer much improvement over off-label use of Harvoni or Viekira Pak for genotype 4 patients. Daklinza is FDA approved in combination with sofosbuvir for 12 weeks for treatment-naive patients with genotype 3 and should also be considered for off-label use for genotype 2 patients.
While SVRs for noncirrhotic treatment-naive genotype 3 patients are high, achieving high SVRs in patients with cirrhosis requires treatment extension to 24 weeks to achieve an SVR around 90% at a cost of nearly $300,000. While this is an improvement on sofosbuvir plus ribavirin for treatment-experienced patients with cirrhosis, it nevertheless is an extremely expensive option that will likely be met with resistance from payers. It will also likely be displaced as a treatment option for genotype 2 and 3 patients when Gilead's pan-genotypic NS5A inhibitor (GS-5816) makes it to market as anticipated within the next year.
Dr. Sean Koppe is director of hepatology at the University of Illinois Hospital & Health Sciences System, Chicago. He has no conflicts of interest.
The recent FDA approval of Daklinza and Technivie for hepatitis C offer some additional weapons in the treatment of hepatitis C; however, their approval does not dramatically alter the treatment landscape at this point. Technivie is FDA approved for genotype 4, a small fraction of patients with hepatitis C, and does not offer much improvement over off-label use of Harvoni or Viekira Pak for genotype 4 patients. Daklinza is FDA approved in combination with sofosbuvir for 12 weeks for treatment-naive patients with genotype 3 and should also be considered for off-label use for genotype 2 patients.
While SVRs for noncirrhotic treatment-naive genotype 3 patients are high, achieving high SVRs in patients with cirrhosis requires treatment extension to 24 weeks to achieve an SVR around 90% at a cost of nearly $300,000. While this is an improvement on sofosbuvir plus ribavirin for treatment-experienced patients with cirrhosis, it nevertheless is an extremely expensive option that will likely be met with resistance from payers. It will also likely be displaced as a treatment option for genotype 2 and 3 patients when Gilead's pan-genotypic NS5A inhibitor (GS-5816) makes it to market as anticipated within the next year.
Dr. Sean Koppe is director of hepatology at the University of Illinois Hospital & Health Sciences System, Chicago. He has no conflicts of interest.
The first interferon-free treatment for people with genotype 4 hepatitis C infection has been approved by the Food and Drug Administration.
On July 24, the FDA approved a combination of three antivirals – ombitasvir, paritaprevir, and ritonavir – for use with ribavirin for treating hepatitis C virus (HCV) genotype 4 infections in people without cirrhosis, according to the agency’s statement announcing the approval. The combination tablet will be marketed as Technivie, by Abbvie. Ombitasvir is an HCV NS5A inhibitor, paritaprevir is an HCV NS3/4A protease inhibitor, and ritonavir is an HCV CYP3A inhibitor.
Technivie “is the first drug that has demonstrated safety and efficacy to treat genotype 4 HCV infections without the need for coadministration of interferon,” the statement said. It is administered orally. Technivie is a fixed-dose combination of paritaprevir/ritonavir (150/100 mg) co-formulated with ombitasvir (25 mg); it is dosed once a day and should be taken with a meal. It is co-administered with weight-based RBV (1000mg or 1200mg in divided doses, twice a day), taken with food, according to the company's statement announcing approval.
The FDA statement refers to that study of 135 people with chronic HCV genotype 4 infections and no cirrhosis, treated with the three antivirals plus ribavirin once a day for 12 weeks (91 patients), or without ribavirin (44 patients) for 12 weeks. All the patients on the three-drug combination plus ribavirin achieved a sustained virologic response (SVR12) 12 weeks after stopping treatment (no HCV detected in the blood) vs. 91% of those who did not take ribavirin. Fatigue, weakness, nausea, insomnia, pruritus and other skin reactions are among the most common adverse events associated with treatment with Technivie and ribavirin, according to the FDA statement.
The statement adds that the prescribing information includes a warning that elevations of liver enzymes up to greater than five times the upper limit of normal occurred in about 1% of the patients in clinical trials, which were more common among women taking contraceptives that contain ethinyl estradiol. Before starting treatment, women should discontinue contraceptives that containing ethinyl estradiol, and “hepatic laboratory testing should be performed during the first 4 weeks of treatment, and as clinically indicated thereafter,” the FDA statement said.
The three antivirals included in Technivie, plus dasabuvir (an HCV nonnucleoside NS5B polymerase inhibitor), are copackaged in the Viekira Pak, which was approved for the treatment of HCV genotype 1 chronic HCV infection, with or without ribavirin in 2014, and is also manufactured by Abbvie.
About 2.7 million people in the United States have chronic HCV infection, according to the Centers for Disease Control and Prevention. HCV genotype 4 is one of the least common types of HCV in the United States.
*This story was updated 7/24/2015.
The first interferon-free treatment for people with genotype 4 hepatitis C infection has been approved by the Food and Drug Administration.
On July 24, the FDA approved a combination of three antivirals – ombitasvir, paritaprevir, and ritonavir – for use with ribavirin for treating hepatitis C virus (HCV) genotype 4 infections in people without cirrhosis, according to the agency’s statement announcing the approval. The combination tablet will be marketed as Technivie, by Abbvie. Ombitasvir is an HCV NS5A inhibitor, paritaprevir is an HCV NS3/4A protease inhibitor, and ritonavir is an HCV CYP3A inhibitor.
Technivie “is the first drug that has demonstrated safety and efficacy to treat genotype 4 HCV infections without the need for coadministration of interferon,” the statement said. It is administered orally. Technivie is a fixed-dose combination of paritaprevir/ritonavir (150/100 mg) co-formulated with ombitasvir (25 mg); it is dosed once a day and should be taken with a meal. It is co-administered with weight-based RBV (1000mg or 1200mg in divided doses, twice a day), taken with food, according to the company's statement announcing approval.
The FDA statement refers to that study of 135 people with chronic HCV genotype 4 infections and no cirrhosis, treated with the three antivirals plus ribavirin once a day for 12 weeks (91 patients), or without ribavirin (44 patients) for 12 weeks. All the patients on the three-drug combination plus ribavirin achieved a sustained virologic response (SVR12) 12 weeks after stopping treatment (no HCV detected in the blood) vs. 91% of those who did not take ribavirin. Fatigue, weakness, nausea, insomnia, pruritus and other skin reactions are among the most common adverse events associated with treatment with Technivie and ribavirin, according to the FDA statement.
The statement adds that the prescribing information includes a warning that elevations of liver enzymes up to greater than five times the upper limit of normal occurred in about 1% of the patients in clinical trials, which were more common among women taking contraceptives that contain ethinyl estradiol. Before starting treatment, women should discontinue contraceptives that containing ethinyl estradiol, and “hepatic laboratory testing should be performed during the first 4 weeks of treatment, and as clinically indicated thereafter,” the FDA statement said.
The three antivirals included in Technivie, plus dasabuvir (an HCV nonnucleoside NS5B polymerase inhibitor), are copackaged in the Viekira Pak, which was approved for the treatment of HCV genotype 1 chronic HCV infection, with or without ribavirin in 2014, and is also manufactured by Abbvie.
About 2.7 million people in the United States have chronic HCV infection, according to the Centers for Disease Control and Prevention. HCV genotype 4 is one of the least common types of HCV in the United States.
*This story was updated 7/24/2015.
