FDA/CDC

Up to 60% of men with erectile dysfunction who were not candidates for phosphodiesterase 5 (PDE5) inhibitors achieved erections in less than 10 minutes after a single application of a first-on-the-market nonprescription gel to the glans, a new study found. 

Wayne Hellstrom, MD, chief of andrology at Tulane School of Medicine in New Orleans, who presented the study of MED3000 [Eroxon] on May 5 at the 2024 annual meeting of the American Urological Association in San Antonio, Texas, said that the gel is considered to be a device by the US Food and Drug Administration (FDA). The agency approved the product in June 2023.

A spokesman for Futura, which makes MED3000, said that the gel will be on the market 2025. No price for the United States has been announced, but a four-pack of single-use tubes sells for the equivalent of roughly $31 in the United Kingdom.

Dr. Hellstrom, a former adviser to Futura, he said he expects MED3000 will be “a potential first-line therapy in addition to PDE5 inhibitors,” which are vasodilating drugs that stimulate the corpora cavernosa of the penis, facilitating erection with sexual stimulation.

He noted that PDE5s are contraindicated for many men; are not tolerated in others; are not completely effective; or work too slowly, taking 1-2 hours to work. As a result, up to 50% of patients cease using a PDE5 inhibitor within 1 year, he said. 

Futura said the gel contains a combination of volatile solvents which, when applied to the head of the penis, evaporate rapidly, stimulating nerve endings through an initial cooling effect followed by a warming sensation. This reaction releases nitric oxide, relaxing the smooth muscle tissue inside the penis and increasing blood flow that is needed to obtain an erection.

Dr. Hellstrom noted that MED3000 is noninvasive and causes no side effects and is slightly more effective if applied by a partner.

The new findings come from two studies of 250 men with erectile dysfunction (FM57) who used MED3000 over 12 weeks and a randomly assigned arm (FM71) with two groups of 48 men who used either MED3000 or 5 mg of tadalafil over 24 weeks.

Erections were achieved in less than 10 minutes in 60.1% of men in the FM57 group and 44.9% of those in the FM71 group.

Overall, less than 2% of the men who usedMED3000 and 4% of those who took tadalafil reported adverse effects. These events included headaches in 3% of the combined MED3000 group and 19.1% of the tadalafil group. Roughly 1% of men who used MED3000 reported penile burning sensation compared with none in the group taking tadalafil.
 

Problematic Design? 

Kevin McVary, MD, a professor of urology at Stritch School of Medicine of Loyola University, outside of Chicago, and director of the Center for Male Health, criticized the study design and added that he did not believe MED3000 had been proven beneficial.

“Are they expecting the Cialis 5 mg to work within 10 minutes? Because it doesn’t,” Dr. McVary said. “It doesn’t get absorbed into the bloodstream for about 2.5 hours.”

Dr. McVary said that men with erectile dysfunction will probably do anything to avoid seeing a physician about the condition, which could make MED3000 highly marketable.

However, he said, examinations would be important to detect unrecognized underlying cardiac disease, especially in younger men. “ED can function as the classic canary in a coal mine where it tells you who’s at risk for unexpected early death,” he said.

Dr. Hellstrom is a former adviser to Futura Medical Developments, which funded the research. Dr. McVary reported no relevant financial conflicts of interest.  
 

A version of this article appeared on Medscape.com .

Up to 60% of men with erectile dysfunction who were not candidates for phosphodiesterase 5 (PDE5) inhibitors achieved erections in less than 10 minutes after a single application of a first-on-the-market nonprescription gel to the glans, a new study found. 

Wayne Hellstrom, MD, chief of andrology at Tulane School of Medicine in New Orleans, who presented the study of MED3000 [Eroxon] on May 5 at the 2024 annual meeting of the American Urological Association in San Antonio, Texas, said that the gel is considered to be a device by the US Food and Drug Administration (FDA). The agency approved the product in June 2023.

A spokesman for Futura, which makes MED3000, said that the gel will be on the market 2025. No price for the United States has been announced, but a four-pack of single-use tubes sells for the equivalent of roughly $31 in the United Kingdom.

Dr. Hellstrom, a former adviser to Futura, he said he expects MED3000 will be “a potential first-line therapy in addition to PDE5 inhibitors,” which are vasodilating drugs that stimulate the corpora cavernosa of the penis, facilitating erection with sexual stimulation.

He noted that PDE5s are contraindicated for many men; are not tolerated in others; are not completely effective; or work too slowly, taking 1-2 hours to work. As a result, up to 50% of patients cease using a PDE5 inhibitor within 1 year, he said. 

Futura said the gel contains a combination of volatile solvents which, when applied to the head of the penis, evaporate rapidly, stimulating nerve endings through an initial cooling effect followed by a warming sensation. This reaction releases nitric oxide, relaxing the smooth muscle tissue inside the penis and increasing blood flow that is needed to obtain an erection.

Dr. Hellstrom noted that MED3000 is noninvasive and causes no side effects and is slightly more effective if applied by a partner.

The new findings come from two studies of 250 men with erectile dysfunction (FM57) who used MED3000 over 12 weeks and a randomly assigned arm (FM71) with two groups of 48 men who used either MED3000 or 5 mg of tadalafil over 24 weeks.

Erections were achieved in less than 10 minutes in 60.1% of men in the FM57 group and 44.9% of those in the FM71 group.

Overall, less than 2% of the men who usedMED3000 and 4% of those who took tadalafil reported adverse effects. These events included headaches in 3% of the combined MED3000 group and 19.1% of the tadalafil group. Roughly 1% of men who used MED3000 reported penile burning sensation compared with none in the group taking tadalafil.
 

Problematic Design? 

Kevin McVary, MD, a professor of urology at Stritch School of Medicine of Loyola University, outside of Chicago, and director of the Center for Male Health, criticized the study design and added that he did not believe MED3000 had been proven beneficial.

“Are they expecting the Cialis 5 mg to work within 10 minutes? Because it doesn’t,” Dr. McVary said. “It doesn’t get absorbed into the bloodstream for about 2.5 hours.”

Dr. McVary said that men with erectile dysfunction will probably do anything to avoid seeing a physician about the condition, which could make MED3000 highly marketable.

However, he said, examinations would be important to detect unrecognized underlying cardiac disease, especially in younger men. “ED can function as the classic canary in a coal mine where it tells you who’s at risk for unexpected early death,” he said.

Dr. Hellstrom is a former adviser to Futura Medical Developments, which funded the research. Dr. McVary reported no relevant financial conflicts of interest.  
 

A version of this article appeared on Medscape.com .

Up to 60% of men with erectile dysfunction who were not candidates for phosphodiesterase 5 (PDE5) inhibitors achieved erections in less than 10 minutes after a single application of a first-on-the-market nonprescription gel to the glans, a new study found. 

Wayne Hellstrom, MD, chief of andrology at Tulane School of Medicine in New Orleans, who presented the study of MED3000 [Eroxon] on May 5 at the 2024 annual meeting of the American Urological Association in San Antonio, Texas, said that the gel is considered to be a device by the US Food and Drug Administration (FDA). The agency approved the product in June 2023.

A spokesman for Futura, which makes MED3000, said that the gel will be on the market 2025. No price for the United States has been announced, but a four-pack of single-use tubes sells for the equivalent of roughly $31 in the United Kingdom.

Dr. Hellstrom, a former adviser to Futura, he said he expects MED3000 will be “a potential first-line therapy in addition to PDE5 inhibitors,” which are vasodilating drugs that stimulate the corpora cavernosa of the penis, facilitating erection with sexual stimulation.

He noted that PDE5s are contraindicated for many men; are not tolerated in others; are not completely effective; or work too slowly, taking 1-2 hours to work. As a result, up to 50% of patients cease using a PDE5 inhibitor within 1 year, he said. 

Futura said the gel contains a combination of volatile solvents which, when applied to the head of the penis, evaporate rapidly, stimulating nerve endings through an initial cooling effect followed by a warming sensation. This reaction releases nitric oxide, relaxing the smooth muscle tissue inside the penis and increasing blood flow that is needed to obtain an erection.

Dr. Hellstrom noted that MED3000 is noninvasive and causes no side effects and is slightly more effective if applied by a partner.

The new findings come from two studies of 250 men with erectile dysfunction (FM57) who used MED3000 over 12 weeks and a randomly assigned arm (FM71) with two groups of 48 men who used either MED3000 or 5 mg of tadalafil over 24 weeks.

Erections were achieved in less than 10 minutes in 60.1% of men in the FM57 group and 44.9% of those in the FM71 group.

Overall, less than 2% of the men who usedMED3000 and 4% of those who took tadalafil reported adverse effects. These events included headaches in 3% of the combined MED3000 group and 19.1% of the tadalafil group. Roughly 1% of men who used MED3000 reported penile burning sensation compared with none in the group taking tadalafil.
 

Problematic Design? 

Kevin McVary, MD, a professor of urology at Stritch School of Medicine of Loyola University, outside of Chicago, and director of the Center for Male Health, criticized the study design and added that he did not believe MED3000 had been proven beneficial.

“Are they expecting the Cialis 5 mg to work within 10 minutes? Because it doesn’t,” Dr. McVary said. “It doesn’t get absorbed into the bloodstream for about 2.5 hours.”

Dr. McVary said that men with erectile dysfunction will probably do anything to avoid seeing a physician about the condition, which could make MED3000 highly marketable.

However, he said, examinations would be important to detect unrecognized underlying cardiac disease, especially in younger men. “ED can function as the classic canary in a coal mine where it tells you who’s at risk for unexpected early death,” he said.

Dr. Hellstrom is a former adviser to Futura Medical Developments, which funded the research. Dr. McVary reported no relevant financial conflicts of interest.  
 

A version of this article appeared on Medscape.com .

The US Food and Drug Administration (FDA) has designated the Eversense (Sensionics, Inc; Ascencia Diabetes Care) implanted continuous glucose monitor (CGM) an “integrated CGM,” meaning it can be used in conjunction with insulin pumps as part of an automated insulin delivery system (AID). 

The Eversense now joins Dexcom’s G6 and G7 and the Freestyle Libre 2 Plus in being compatible with multiple different branded insulin pumps as part of AID systems, and it is the only implantable one. 

The sensor device is inserted under the skin of the patient’s upper arm by a healthcare provider and a transmitter is worn over it on the skin. The FDA approved the Eversense in June 2018 for 3-month use and in February 2022  for use up to 6 months. It is indicated for people with diabetes aged 18 years and older.

Fingerstick blood glucose measurements are still required for calibration once a day after day 21, when symptoms don’t match the CGM information, or when taking tetracycline medications. 

According to Sensionics, the Eversense is “the most accurate CGM in the critical low glucose ranges with essentially no compression lows.” The latter refers to ‘false low’ alarms that sometimes occur when a person presses on the device, such as during sleep.

“As we look ahead, we are focused on progressing our partnership discussions and software developments, and look forward to providing more updates,” Sensionics said in a statement.
 

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has designated the Eversense (Sensionics, Inc; Ascencia Diabetes Care) implanted continuous glucose monitor (CGM) an “integrated CGM,” meaning it can be used in conjunction with insulin pumps as part of an automated insulin delivery system (AID). 

The Eversense now joins Dexcom’s G6 and G7 and the Freestyle Libre 2 Plus in being compatible with multiple different branded insulin pumps as part of AID systems, and it is the only implantable one. 

The sensor device is inserted under the skin of the patient’s upper arm by a healthcare provider and a transmitter is worn over it on the skin. The FDA approved the Eversense in June 2018 for 3-month use and in February 2022  for use up to 6 months. It is indicated for people with diabetes aged 18 years and older.

Fingerstick blood glucose measurements are still required for calibration once a day after day 21, when symptoms don’t match the CGM information, or when taking tetracycline medications. 

According to Sensionics, the Eversense is “the most accurate CGM in the critical low glucose ranges with essentially no compression lows.” The latter refers to ‘false low’ alarms that sometimes occur when a person presses on the device, such as during sleep.

“As we look ahead, we are focused on progressing our partnership discussions and software developments, and look forward to providing more updates,” Sensionics said in a statement.
 

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has designated the Eversense (Sensionics, Inc; Ascencia Diabetes Care) implanted continuous glucose monitor (CGM) an “integrated CGM,” meaning it can be used in conjunction with insulin pumps as part of an automated insulin delivery system (AID). 

The Eversense now joins Dexcom’s G6 and G7 and the Freestyle Libre 2 Plus in being compatible with multiple different branded insulin pumps as part of AID systems, and it is the only implantable one. 

The sensor device is inserted under the skin of the patient’s upper arm by a healthcare provider and a transmitter is worn over it on the skin. The FDA approved the Eversense in June 2018 for 3-month use and in February 2022  for use up to 6 months. It is indicated for people with diabetes aged 18 years and older.

Fingerstick blood glucose measurements are still required for calibration once a day after day 21, when symptoms don’t match the CGM information, or when taking tetracycline medications. 

According to Sensionics, the Eversense is “the most accurate CGM in the critical low glucose ranges with essentially no compression lows.” The latter refers to ‘false low’ alarms that sometimes occur when a person presses on the device, such as during sleep.

“As we look ahead, we are focused on progressing our partnership discussions and software developments, and look forward to providing more updates,” Sensionics said in a statement.
 

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved a new treatment for uncomplicated urinary tract infections (UTIs). 

The agency on April 24 approved pivmecillinam tablets to treat women aged 18 years or older with UTIs caused by bacteria susceptible to the drug.

The beta-lactam antibiotic already is approved in Europe and has been used for more than 40 years outside of the United States to treat infections, according to the drug’s manufacturer, Utility Therapeutics. 

The drug is an aminopenicillin that rapidly converts to mecillinam, according to the company, which is marketing the medication as Pivya. 

Pivmecillinam is intended to treat UTIs caused by susceptible isolates of Escherichia coli, Proteus mirabilis, and Staphylococcus saprophyticus. 

Researchers studied the treatment in three clinical trials. One study found women who received the new antibiotic were more likely to have resolution of symptoms and a reduction in bacteria in urine compared with placebo (62% vs 10%). Similar results were seen in a trial that used ibuprofen as the comparator (66% vs 22%). 

In a third study that assessed two oral antibacterial drugs, 72% of women who received pivmecillinam and 76% who received the other drug achieved resolution of symptoms and a reduction in bacteria, according to the FDA. 

The most common side effects of pivmecillinam include nausea and diarrhea.

About half of all women will experience at least one UTI in their lifetime, and the infections are one the top reasons for antibiotic prescriptions, the FDA noted. 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved a new treatment for uncomplicated urinary tract infections (UTIs). 

The agency on April 24 approved pivmecillinam tablets to treat women aged 18 years or older with UTIs caused by bacteria susceptible to the drug.

The beta-lactam antibiotic already is approved in Europe and has been used for more than 40 years outside of the United States to treat infections, according to the drug’s manufacturer, Utility Therapeutics. 

The drug is an aminopenicillin that rapidly converts to mecillinam, according to the company, which is marketing the medication as Pivya. 

Pivmecillinam is intended to treat UTIs caused by susceptible isolates of Escherichia coli, Proteus mirabilis, and Staphylococcus saprophyticus. 

Researchers studied the treatment in three clinical trials. One study found women who received the new antibiotic were more likely to have resolution of symptoms and a reduction in bacteria in urine compared with placebo (62% vs 10%). Similar results were seen in a trial that used ibuprofen as the comparator (66% vs 22%). 

In a third study that assessed two oral antibacterial drugs, 72% of women who received pivmecillinam and 76% who received the other drug achieved resolution of symptoms and a reduction in bacteria, according to the FDA. 

The most common side effects of pivmecillinam include nausea and diarrhea.

About half of all women will experience at least one UTI in their lifetime, and the infections are one the top reasons for antibiotic prescriptions, the FDA noted. 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved a new treatment for uncomplicated urinary tract infections (UTIs). 

The agency on April 24 approved pivmecillinam tablets to treat women aged 18 years or older with UTIs caused by bacteria susceptible to the drug.

The beta-lactam antibiotic already is approved in Europe and has been used for more than 40 years outside of the United States to treat infections, according to the drug’s manufacturer, Utility Therapeutics. 

The drug is an aminopenicillin that rapidly converts to mecillinam, according to the company, which is marketing the medication as Pivya. 

Pivmecillinam is intended to treat UTIs caused by susceptible isolates of Escherichia coli, Proteus mirabilis, and Staphylococcus saprophyticus. 

Researchers studied the treatment in three clinical trials. One study found women who received the new antibiotic were more likely to have resolution of symptoms and a reduction in bacteria in urine compared with placebo (62% vs 10%). Similar results were seen in a trial that used ibuprofen as the comparator (66% vs 22%). 

In a third study that assessed two oral antibacterial drugs, 72% of women who received pivmecillinam and 76% who received the other drug achieved resolution of symptoms and a reduction in bacteria, according to the FDA. 

The most common side effects of pivmecillinam include nausea and diarrhea.

About half of all women will experience at least one UTI in their lifetime, and the infections are one the top reasons for antibiotic prescriptions, the FDA noted. 

A version of this article appeared on Medscape.com.

The Food and Drug Administration (FDA) has issued a complete response letter regarding the Biologics License Application (BLA) for prademagene zamikeracel (pz-cel), which is under review for the treatment of patients with recessive dystrophic epidermolysis bullosa (RDEB), requesting more information from the manufacturer.

Pz-cel, which comprises autologous, COL7A1 gene–corrected epidermal sheets, is being evaluated for its ability to enable normal type VII collagen expression in a patient’s skin cells and to facilitate wound healing and pain reduction in wounds in patients with RDEB after a one-time application procedure. The cause of RDEB is a defect in the COL7A1 gene that “results in the inability to produce type VII collagen,” a press release from the manufacturer noted.

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On April 22, 2024, the manufacturer Abeona Therapeutics announced that following a meeting with the FDA in March and in a subsequent request for information, the agency requires additional information to satisfy certain Chemistry Manufacturing and Controls requirements before the BLA for pz-cel can be approved. According to a press release from the company, the information pertains to validation requirements for certain manufacturing and release testing methods, including some that were observed during the FDA’s pre-licensing inspection.

The complete response letter did not identify any issues related to the clinical efficacy or safety data in the BLA, and the FDA did not request any new clinical trials or clinical data to support approval, according to the company.

The company anticipates completing the BLA resubmission in the third quarter of 2024. The application is supported by clinical efficacy and safety data from the pivotal phase 3 VIITAL study and a phase 1/2a study in patients with RDEB.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration (FDA) has issued a complete response letter regarding the Biologics License Application (BLA) for prademagene zamikeracel (pz-cel), which is under review for the treatment of patients with recessive dystrophic epidermolysis bullosa (RDEB), requesting more information from the manufacturer.

Pz-cel, which comprises autologous, COL7A1 gene–corrected epidermal sheets, is being evaluated for its ability to enable normal type VII collagen expression in a patient’s skin cells and to facilitate wound healing and pain reduction in wounds in patients with RDEB after a one-time application procedure. The cause of RDEB is a defect in the COL7A1 gene that “results in the inability to produce type VII collagen,” a press release from the manufacturer noted.

[embed:render:related:node:264410]

On April 22, 2024, the manufacturer Abeona Therapeutics announced that following a meeting with the FDA in March and in a subsequent request for information, the agency requires additional information to satisfy certain Chemistry Manufacturing and Controls requirements before the BLA for pz-cel can be approved. According to a press release from the company, the information pertains to validation requirements for certain manufacturing and release testing methods, including some that were observed during the FDA’s pre-licensing inspection.

The complete response letter did not identify any issues related to the clinical efficacy or safety data in the BLA, and the FDA did not request any new clinical trials or clinical data to support approval, according to the company.

The company anticipates completing the BLA resubmission in the third quarter of 2024. The application is supported by clinical efficacy and safety data from the pivotal phase 3 VIITAL study and a phase 1/2a study in patients with RDEB.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration (FDA) has issued a complete response letter regarding the Biologics License Application (BLA) for prademagene zamikeracel (pz-cel), which is under review for the treatment of patients with recessive dystrophic epidermolysis bullosa (RDEB), requesting more information from the manufacturer.

Pz-cel, which comprises autologous, COL7A1 gene–corrected epidermal sheets, is being evaluated for its ability to enable normal type VII collagen expression in a patient’s skin cells and to facilitate wound healing and pain reduction in wounds in patients with RDEB after a one-time application procedure. The cause of RDEB is a defect in the COL7A1 gene that “results in the inability to produce type VII collagen,” a press release from the manufacturer noted.

[embed:render:related:node:264410]

On April 22, 2024, the manufacturer Abeona Therapeutics announced that following a meeting with the FDA in March and in a subsequent request for information, the agency requires additional information to satisfy certain Chemistry Manufacturing and Controls requirements before the BLA for pz-cel can be approved. According to a press release from the company, the information pertains to validation requirements for certain manufacturing and release testing methods, including some that were observed during the FDA’s pre-licensing inspection.

The complete response letter did not identify any issues related to the clinical efficacy or safety data in the BLA, and the FDA did not request any new clinical trials or clinical data to support approval, according to the company.

The company anticipates completing the BLA resubmission in the third quarter of 2024. The application is supported by clinical efficacy and safety data from the pivotal phase 3 VIITAL study and a phase 1/2a study in patients with RDEB.

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the gene therapy fidanacogene elaparvovec (Beqvez) for adults with hemophilia B, a rare bleeding disorder that affects almost 4 in 100,000 US men.

Patients are eligible for a one-time infusion of Pfizer’s gene therapy if they are currently using clotting factor IX prophylaxis therapy; have current or historical life-threatening hemorrhages; or have repeated, serious spontaneous bleeding episodes. 

Beqvez is the second gene therapy the agency has approved for hemophilia B, a deficiency in clotting factor IX because of a faulty gene that occurs mostly in males. The FDA approved the first gene therapy, etranacogene dezaparvovec (Hemgenix), in November 2022. 

Both therapies deliver a functional copy of the factor IX gene to liver cells via a viral vector. 

Pfizer said the list price of Beqvez will be $3.5 million — the same price as Hemgenix. The argument for this hefty price tag is that these gene therapies offer the possibility of a cure whereas ongoing factor IX infusions can cost more than $20 million over a patient’s lifetime. Uptake of Hemgenix, however, has been slow, given the cost and concerns about the therapy’s durability and safety.

Beqvez was approved on the basis of the phase 3 BENEGENE-2 trial in 45 men with moderate to severe hemophilia B. These men had been on factor IX prophylaxis for at least 6 months and had tested negative for antibodies against the viral delivery vector. 

The annualized bleeding rate fell from a mean of 4.5 events during the pretreatment period of at least 6 months to a mean of 2.5 events between week 12 and data cutoff (median, 1.8 years of follow-up), according to Pfizer’s press release. Overall, bleeding events were eliminated in 60% of patients who received the one-time infusion vs 29% of patients on factor IX prophylaxis therapy.

Overall, Pfizer reported that the gene therapy was “generally well-tolerated,” with an increase in transaminases reported as the most common adverse event. No deaths, serious infusion reactions, thrombotic events, or development of factor IX antibodies occurred. 

Pfizer has said it will continue to monitor patients to assess the therapy’s long-term durability and safety over a 15-year period.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the gene therapy fidanacogene elaparvovec (Beqvez) for adults with hemophilia B, a rare bleeding disorder that affects almost 4 in 100,000 US men.

Patients are eligible for a one-time infusion of Pfizer’s gene therapy if they are currently using clotting factor IX prophylaxis therapy; have current or historical life-threatening hemorrhages; or have repeated, serious spontaneous bleeding episodes. 

Beqvez is the second gene therapy the agency has approved for hemophilia B, a deficiency in clotting factor IX because of a faulty gene that occurs mostly in males. The FDA approved the first gene therapy, etranacogene dezaparvovec (Hemgenix), in November 2022. 

Both therapies deliver a functional copy of the factor IX gene to liver cells via a viral vector. 

Pfizer said the list price of Beqvez will be $3.5 million — the same price as Hemgenix. The argument for this hefty price tag is that these gene therapies offer the possibility of a cure whereas ongoing factor IX infusions can cost more than $20 million over a patient’s lifetime. Uptake of Hemgenix, however, has been slow, given the cost and concerns about the therapy’s durability and safety.

Beqvez was approved on the basis of the phase 3 BENEGENE-2 trial in 45 men with moderate to severe hemophilia B. These men had been on factor IX prophylaxis for at least 6 months and had tested negative for antibodies against the viral delivery vector. 

The annualized bleeding rate fell from a mean of 4.5 events during the pretreatment period of at least 6 months to a mean of 2.5 events between week 12 and data cutoff (median, 1.8 years of follow-up), according to Pfizer’s press release. Overall, bleeding events were eliminated in 60% of patients who received the one-time infusion vs 29% of patients on factor IX prophylaxis therapy.

Overall, Pfizer reported that the gene therapy was “generally well-tolerated,” with an increase in transaminases reported as the most common adverse event. No deaths, serious infusion reactions, thrombotic events, or development of factor IX antibodies occurred. 

Pfizer has said it will continue to monitor patients to assess the therapy’s long-term durability and safety over a 15-year period.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the gene therapy fidanacogene elaparvovec (Beqvez) for adults with hemophilia B, a rare bleeding disorder that affects almost 4 in 100,000 US men.

Patients are eligible for a one-time infusion of Pfizer’s gene therapy if they are currently using clotting factor IX prophylaxis therapy; have current or historical life-threatening hemorrhages; or have repeated, serious spontaneous bleeding episodes. 

Beqvez is the second gene therapy the agency has approved for hemophilia B, a deficiency in clotting factor IX because of a faulty gene that occurs mostly in males. The FDA approved the first gene therapy, etranacogene dezaparvovec (Hemgenix), in November 2022. 

Both therapies deliver a functional copy of the factor IX gene to liver cells via a viral vector. 

Pfizer said the list price of Beqvez will be $3.5 million — the same price as Hemgenix. The argument for this hefty price tag is that these gene therapies offer the possibility of a cure whereas ongoing factor IX infusions can cost more than $20 million over a patient’s lifetime. Uptake of Hemgenix, however, has been slow, given the cost and concerns about the therapy’s durability and safety.

Beqvez was approved on the basis of the phase 3 BENEGENE-2 trial in 45 men with moderate to severe hemophilia B. These men had been on factor IX prophylaxis for at least 6 months and had tested negative for antibodies against the viral delivery vector. 

The annualized bleeding rate fell from a mean of 4.5 events during the pretreatment period of at least 6 months to a mean of 2.5 events between week 12 and data cutoff (median, 1.8 years of follow-up), according to Pfizer’s press release. Overall, bleeding events were eliminated in 60% of patients who received the one-time infusion vs 29% of patients on factor IX prophylaxis therapy.

Overall, Pfizer reported that the gene therapy was “generally well-tolerated,” with an increase in transaminases reported as the most common adverse event. No deaths, serious infusion reactions, thrombotic events, or development of factor IX antibodies occurred. 

Pfizer has said it will continue to monitor patients to assess the therapy’s long-term durability and safety over a 15-year period.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the first-in-class interleukin (IL)-15 superagonist nogapendekin alfa inbakicept-pmln (Anktiva), plus bacillus Calmette-Guérin (BCG), for the treatment of certain non–muscle-invasive bladder cancers that fail to respond to BCG alone.

Specifically, the agent is approved to treat patients with BCG-unresponsive non–muscle-invasive bladder cancer carcinoma in situ with or without Ta or T1 papillary disease. 

The FDA declined an initial approval for the combination in May 2023 because of deficiencies the agency observed during its prelicense inspection of third-party manufacturing organizations. In October 2023, ImmunityBio resubmitted the Biologics License Application, which was accepted.

The new therapy represents addresses “an unmet need” in this high-risk bladder cancer population, the company stated in a press release announcing the initial study findings. Typically, patients with intermediate or high-risk disease undergo bladder tumor resection followed by treatment with BCG, but the cancer recurs in up to 50% of patients, including those who experience a complete response, explained ImmunityBio, which acquired Altor BioScience. 

Approval was based on findings from the single arm, phase 2/3 open-label QUILT-3.032 study, which included 77 patients with BCG-unresponsive, high-risk disease following transurethral resection. All had Eastern Cooperative Oncology Group performance status of 0-2. 

Patients received nogapendekin alfa inbakicept-pmln induction via intravesical instillation with BCG followed by maintenance therapy for up to 37 months. 

According to the FDA’s press release, 62% of patients had a complete response, defined as a negative cystoscopy and urine cytology; 58% of those with a complete response had a duration of response lasting at least 12 months and 40% had a duration of response lasting 24 months or longer.

The safety of the combination was evaluated in a cohort of 88 patients. Serious adverse reactions occurred in 16% of patients. The most common treatment-emergent adverse effects included dysuria, pollakiuria, and hematuria, which are associated with intravesical BCG; 86% of these events were grade 1 or 2. Overall, 7% of patients discontinued the combination owing to adverse reactions.

The recommended dose is 400 mcg administered intravesically with BCG once a week for 6 weeks as induction therapy, with an option for a second induction course if patients don’t achieve a complete response at 3 months. The recommended maintenance therapy dose is 400 mcg with BCG once a week for 3 weeks at months 4, 7, 10, 13, and 19. Patients who achieve a complete response at 25 months and beyond may receive maintenance instillations with BCG once a week for 3 weeks at months 25, 31, and 37. The maximum treatment duration is 37 months.

The FDA recommends discontinuing treatment if disease persists after second induction or owing to disease recurrence, progression, or unacceptable toxicity. 
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the first-in-class interleukin (IL)-15 superagonist nogapendekin alfa inbakicept-pmln (Anktiva), plus bacillus Calmette-Guérin (BCG), for the treatment of certain non–muscle-invasive bladder cancers that fail to respond to BCG alone.

Specifically, the agent is approved to treat patients with BCG-unresponsive non–muscle-invasive bladder cancer carcinoma in situ with or without Ta or T1 papillary disease. 

The FDA declined an initial approval for the combination in May 2023 because of deficiencies the agency observed during its prelicense inspection of third-party manufacturing organizations. In October 2023, ImmunityBio resubmitted the Biologics License Application, which was accepted.

The new therapy represents addresses “an unmet need” in this high-risk bladder cancer population, the company stated in a press release announcing the initial study findings. Typically, patients with intermediate or high-risk disease undergo bladder tumor resection followed by treatment with BCG, but the cancer recurs in up to 50% of patients, including those who experience a complete response, explained ImmunityBio, which acquired Altor BioScience. 

Approval was based on findings from the single arm, phase 2/3 open-label QUILT-3.032 study, which included 77 patients with BCG-unresponsive, high-risk disease following transurethral resection. All had Eastern Cooperative Oncology Group performance status of 0-2. 

Patients received nogapendekin alfa inbakicept-pmln induction via intravesical instillation with BCG followed by maintenance therapy for up to 37 months. 

According to the FDA’s press release, 62% of patients had a complete response, defined as a negative cystoscopy and urine cytology; 58% of those with a complete response had a duration of response lasting at least 12 months and 40% had a duration of response lasting 24 months or longer.

The safety of the combination was evaluated in a cohort of 88 patients. Serious adverse reactions occurred in 16% of patients. The most common treatment-emergent adverse effects included dysuria, pollakiuria, and hematuria, which are associated with intravesical BCG; 86% of these events were grade 1 or 2. Overall, 7% of patients discontinued the combination owing to adverse reactions.

The recommended dose is 400 mcg administered intravesically with BCG once a week for 6 weeks as induction therapy, with an option for a second induction course if patients don’t achieve a complete response at 3 months. The recommended maintenance therapy dose is 400 mcg with BCG once a week for 3 weeks at months 4, 7, 10, 13, and 19. Patients who achieve a complete response at 25 months and beyond may receive maintenance instillations with BCG once a week for 3 weeks at months 25, 31, and 37. The maximum treatment duration is 37 months.

The FDA recommends discontinuing treatment if disease persists after second induction or owing to disease recurrence, progression, or unacceptable toxicity. 
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the first-in-class interleukin (IL)-15 superagonist nogapendekin alfa inbakicept-pmln (Anktiva), plus bacillus Calmette-Guérin (BCG), for the treatment of certain non–muscle-invasive bladder cancers that fail to respond to BCG alone.

Specifically, the agent is approved to treat patients with BCG-unresponsive non–muscle-invasive bladder cancer carcinoma in situ with or without Ta or T1 papillary disease. 

The FDA declined an initial approval for the combination in May 2023 because of deficiencies the agency observed during its prelicense inspection of third-party manufacturing organizations. In October 2023, ImmunityBio resubmitted the Biologics License Application, which was accepted.

The new therapy represents addresses “an unmet need” in this high-risk bladder cancer population, the company stated in a press release announcing the initial study findings. Typically, patients with intermediate or high-risk disease undergo bladder tumor resection followed by treatment with BCG, but the cancer recurs in up to 50% of patients, including those who experience a complete response, explained ImmunityBio, which acquired Altor BioScience. 

Approval was based on findings from the single arm, phase 2/3 open-label QUILT-3.032 study, which included 77 patients with BCG-unresponsive, high-risk disease following transurethral resection. All had Eastern Cooperative Oncology Group performance status of 0-2. 

Patients received nogapendekin alfa inbakicept-pmln induction via intravesical instillation with BCG followed by maintenance therapy for up to 37 months. 

According to the FDA’s press release, 62% of patients had a complete response, defined as a negative cystoscopy and urine cytology; 58% of those with a complete response had a duration of response lasting at least 12 months and 40% had a duration of response lasting 24 months or longer.

The safety of the combination was evaluated in a cohort of 88 patients. Serious adverse reactions occurred in 16% of patients. The most common treatment-emergent adverse effects included dysuria, pollakiuria, and hematuria, which are associated with intravesical BCG; 86% of these events were grade 1 or 2. Overall, 7% of patients discontinued the combination owing to adverse reactions.

The recommended dose is 400 mcg administered intravesically with BCG once a week for 6 weeks as induction therapy, with an option for a second induction course if patients don’t achieve a complete response at 3 months. The recommended maintenance therapy dose is 400 mcg with BCG once a week for 3 weeks at months 4, 7, 10, 13, and 19. Patients who achieve a complete response at 25 months and beyond may receive maintenance instillations with BCG once a week for 3 weeks at months 25, 31, and 37. The maximum treatment duration is 37 months.

The FDA recommends discontinuing treatment if disease persists after second induction or owing to disease recurrence, progression, or unacceptable toxicity. 
 

A version of this article appeared on Medscape.com.

TOPLINE:

An analysis of molecular-targeted cancer drug therapies recently approved in the United States found that fewer than one-third demonstrated substantial clinical benefits at the time of approval.

METHODOLOGY:

• The strength and quality of evidence supporting genome-targeted cancer drug approvals vary. A big reason is the growing number of cancer drug approvals based on surrogate endpoints, such as disease-free and progression-free survival, instead of clinical endpoints, such as overall survival or quality of life. The US Food and Drug Administration (FDA) has also approved genome-targeted cancer drugs based on phase 1 or single-arm trials.
• Given these less rigorous considerations for approval, “the validity and value of the targets and surrogate measures underlying FDA genome-targeted cancer drug approvals are uncertain,” the researchers explained.
• In the current analysis, researchers assessed the validity of the molecular targets as well as the clinical benefits of genome-targeted cancer drugs approved in the United States from 2015 to 2022 based on results from pivotal trials.
• The researchers evaluated the strength of evidence supporting molecular targetability using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) and the clinical benefit using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS).
• The authors defined a substantial clinical benefit as an A or B grade for curative intent and a 4 or 5 for noncurative intent. High-benefit genomic-based cancer treatments were defined as those associated with a substantial clinical benefit (ESMO-MCBS) and that qualified as ESCAT category level I-A (a clinical benefit based on prospective randomized data) or I-B (prospective nonrandomized data).

TAKEAWAY:

• The analyses focused on 50 molecular-targeted cancer drugs covering 84 indications. Of which, 45 indications (54%) were approved based on phase 1 or 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials and the remaining 39 (46%) by randomized trial, and 48 (57%) were approved based on subgroup analyses.
• Among the 84 indications, more than half (55%) of the pivotal trials supporting approval used overall response rate as a primary endpoint, 31% used progression-free survival, and 6% used disease-free survival. Only seven indications (8%) were supported by pivotal trials demonstrating an improvement in overall survival.
• Among the 84 trials, 24 (29%) met the ESMO-MCBS threshold for substantial clinical benefit.
• Overall, when combining all ratings, only 24 of the 84 indications (29%) were considered high-benefit genomic-based cancer treatments.

IN PRACTICE:

“We applied the ESMO-MCBS and ESCAT value frameworks to identify therapies and molecular targets providing high clinical value that should be widely available to patients” and “found that drug indications supported by these characteristics represent a minority of cancer drug approvals in recent years,” the authors said. Using these value frameworks could help payers, governments, and individual patients “prioritize the availability of high-value molecular-targeted therapies.”

SOURCE:

The study, with first author Ariadna Tibau, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in JAMA Oncology.

LIMITATIONS:

The study evaluated only trials that supported regulatory approval and did not include outcomes of postapproval clinical studies, which could lead to changes in ESMO-MCBS grades and ESCAT levels of evidence over time.

DISCLOSURES:

The study was funded by the Kaiser Permanente Institute for Health Policy, Arnold Ventures, and the Commonwealth Fund. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

An analysis of molecular-targeted cancer drug therapies recently approved in the United States found that fewer than one-third demonstrated substantial clinical benefits at the time of approval.

METHODOLOGY:

• The strength and quality of evidence supporting genome-targeted cancer drug approvals vary. A big reason is the growing number of cancer drug approvals based on surrogate endpoints, such as disease-free and progression-free survival, instead of clinical endpoints, such as overall survival or quality of life. The US Food and Drug Administration (FDA) has also approved genome-targeted cancer drugs based on phase 1 or single-arm trials.
• Given these less rigorous considerations for approval, “the validity and value of the targets and surrogate measures underlying FDA genome-targeted cancer drug approvals are uncertain,” the researchers explained.
• In the current analysis, researchers assessed the validity of the molecular targets as well as the clinical benefits of genome-targeted cancer drugs approved in the United States from 2015 to 2022 based on results from pivotal trials.
• The researchers evaluated the strength of evidence supporting molecular targetability using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) and the clinical benefit using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS).
• The authors defined a substantial clinical benefit as an A or B grade for curative intent and a 4 or 5 for noncurative intent. High-benefit genomic-based cancer treatments were defined as those associated with a substantial clinical benefit (ESMO-MCBS) and that qualified as ESCAT category level I-A (a clinical benefit based on prospective randomized data) or I-B (prospective nonrandomized data).

TAKEAWAY:

• The analyses focused on 50 molecular-targeted cancer drugs covering 84 indications. Of which, 45 indications (54%) were approved based on phase 1 or 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials and the remaining 39 (46%) by randomized trial, and 48 (57%) were approved based on subgroup analyses.
• Among the 84 indications, more than half (55%) of the pivotal trials supporting approval used overall response rate as a primary endpoint, 31% used progression-free survival, and 6% used disease-free survival. Only seven indications (8%) were supported by pivotal trials demonstrating an improvement in overall survival.
• Among the 84 trials, 24 (29%) met the ESMO-MCBS threshold for substantial clinical benefit.
• Overall, when combining all ratings, only 24 of the 84 indications (29%) were considered high-benefit genomic-based cancer treatments.

IN PRACTICE:

“We applied the ESMO-MCBS and ESCAT value frameworks to identify therapies and molecular targets providing high clinical value that should be widely available to patients” and “found that drug indications supported by these characteristics represent a minority of cancer drug approvals in recent years,” the authors said. Using these value frameworks could help payers, governments, and individual patients “prioritize the availability of high-value molecular-targeted therapies.”

SOURCE:

The study, with first author Ariadna Tibau, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in JAMA Oncology.

LIMITATIONS:

The study evaluated only trials that supported regulatory approval and did not include outcomes of postapproval clinical studies, which could lead to changes in ESMO-MCBS grades and ESCAT levels of evidence over time.

DISCLOSURES:

The study was funded by the Kaiser Permanente Institute for Health Policy, Arnold Ventures, and the Commonwealth Fund. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

An analysis of molecular-targeted cancer drug therapies recently approved in the United States found that fewer than one-third demonstrated substantial clinical benefits at the time of approval.

METHODOLOGY:

• The strength and quality of evidence supporting genome-targeted cancer drug approvals vary. A big reason is the growing number of cancer drug approvals based on surrogate endpoints, such as disease-free and progression-free survival, instead of clinical endpoints, such as overall survival or quality of life. The US Food and Drug Administration (FDA) has also approved genome-targeted cancer drugs based on phase 1 or single-arm trials.
• Given these less rigorous considerations for approval, “the validity and value of the targets and surrogate measures underlying FDA genome-targeted cancer drug approvals are uncertain,” the researchers explained.
• In the current analysis, researchers assessed the validity of the molecular targets as well as the clinical benefits of genome-targeted cancer drugs approved in the United States from 2015 to 2022 based on results from pivotal trials.
• The researchers evaluated the strength of evidence supporting molecular targetability using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) and the clinical benefit using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS).
• The authors defined a substantial clinical benefit as an A or B grade for curative intent and a 4 or 5 for noncurative intent. High-benefit genomic-based cancer treatments were defined as those associated with a substantial clinical benefit (ESMO-MCBS) and that qualified as ESCAT category level I-A (a clinical benefit based on prospective randomized data) or I-B (prospective nonrandomized data).

TAKEAWAY:

• The analyses focused on 50 molecular-targeted cancer drugs covering 84 indications. Of which, 45 indications (54%) were approved based on phase 1 or 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials and the remaining 39 (46%) by randomized trial, and 48 (57%) were approved based on subgroup analyses.
• Among the 84 indications, more than half (55%) of the pivotal trials supporting approval used overall response rate as a primary endpoint, 31% used progression-free survival, and 6% used disease-free survival. Only seven indications (8%) were supported by pivotal trials demonstrating an improvement in overall survival.
• Among the 84 trials, 24 (29%) met the ESMO-MCBS threshold for substantial clinical benefit.
• Overall, when combining all ratings, only 24 of the 84 indications (29%) were considered high-benefit genomic-based cancer treatments.

IN PRACTICE:

“We applied the ESMO-MCBS and ESCAT value frameworks to identify therapies and molecular targets providing high clinical value that should be widely available to patients” and “found that drug indications supported by these characteristics represent a minority of cancer drug approvals in recent years,” the authors said. Using these value frameworks could help payers, governments, and individual patients “prioritize the availability of high-value molecular-targeted therapies.”

SOURCE:

The study, with first author Ariadna Tibau, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in JAMA Oncology.

LIMITATIONS:

The study evaluated only trials that supported regulatory approval and did not include outcomes of postapproval clinical studies, which could lead to changes in ESMO-MCBS grades and ESCAT levels of evidence over time.

DISCLOSURES:

The study was funded by the Kaiser Permanente Institute for Health Policy, Arnold Ventures, and the Commonwealth Fund. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

At least 19 people from nine states have reported serious reactions after receiving botulinum toxin injections from unlicensed or untrained individuals or in non-healthcare settings, such as homes and spas, according to an announcement of an investigation into these reports from the Centers for Disease Control and Prevention posted online April 15.

Reactions have included blurry vision, double vision, drooping eyelids, difficult swallowing or breathing, and other symptoms of botulism.

Of the 19 individuals — all of whom identified as female and had a mean age of 39 years — 9 (60%) were hospitalized and 4 (21%) were treated with botulism antitoxin because of concerns that the botulinum toxin could have spread beyond the injection site. Also, five were tested for botulism and their results were negative.

The CDC, several state and local health departments, and the US Food and Drug Administration (FDA) are investigating these reports, according to the announcement.

CDC_icon_web.jpg

States reporting these cases include Colorado, Florida, Illinois, Kentucky, Nebraska, New Jersey, New York, Tennessee, and Washington. According to the CDC summary, some of the individuals “received injections with counterfeit products or products with unverified sources. Investigation into the sources of these products is ongoing.” All but one report involved receiving botulinum toxin injections for cosmetic purposes.

Recent cases of botulism-like illnesses possibly related to counterfeit botulinum toxin reported in Illinois and Tennessee, prompted the American Society for Dermatologic Surgery Association (ASDSA) to call on states to increase oversight of medical care in all settings, including medical spas, the ASDSA announced on April 12.

[embed:render:related:node:267216]

The CDC summary advises clinicians to consider the possibility of adverse effects from botulinum toxin injection, including for cosmetic reasons, when patients present with signs and symptoms consistent with botulism near the injection site. Symptoms of botulism include blurry or double vision, drooping eyelids, difficulty swallowing, difficulty breathing, and muscle weakness.

For people who are considering botulinum toxin for cosmetic or medical reasons, recommendations from the CDC include asking the provider and setting, such as a clinic or spa, if they are licensed and trained to provide these injections, and to ask if the product is approved by the FDA and from a reliable source, and, “if in doubt, don’t get the injection.”

This ‘Should Never Happen’

“The report of people getting botulism from botulinum toxin injections is frightening, and should never happen,” Lawrence J. Green, MD, clinical professor of dermatology, George Washington University, Washington, told this news organization.

Green_Lawrence_J_MD_web.jpg

These reports show “how important it is to receive botulinum toxin injections only in a medical office, and from or under the direction of a qualified, trained, and licensed individual, like a board certified dermatologist,” added Dr. Green, who practices in Rockville, Maryland. “Other types of practitioners may not adhere to the same standards of professionalism, especially not always putting patient safety first.”

Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.
 

For cases of suspected systemic botulism, the CDC recommends calling the local or state health department for consultation and antitoxin release (as well as information on reporting adverse events). Alternatively, the 24/7 phone number for the CDC clinical botulism service is 770-488-7100.

At least 19 people from nine states have reported serious reactions after receiving botulinum toxin injections from unlicensed or untrained individuals or in non-healthcare settings, such as homes and spas, according to an announcement of an investigation into these reports from the Centers for Disease Control and Prevention posted online April 15.

Reactions have included blurry vision, double vision, drooping eyelids, difficult swallowing or breathing, and other symptoms of botulism.

Of the 19 individuals — all of whom identified as female and had a mean age of 39 years — 9 (60%) were hospitalized and 4 (21%) were treated with botulism antitoxin because of concerns that the botulinum toxin could have spread beyond the injection site. Also, five were tested for botulism and their results were negative.

The CDC, several state and local health departments, and the US Food and Drug Administration (FDA) are investigating these reports, according to the announcement.

CDC_icon_web.jpg

States reporting these cases include Colorado, Florida, Illinois, Kentucky, Nebraska, New Jersey, New York, Tennessee, and Washington. According to the CDC summary, some of the individuals “received injections with counterfeit products or products with unverified sources. Investigation into the sources of these products is ongoing.” All but one report involved receiving botulinum toxin injections for cosmetic purposes.

Recent cases of botulism-like illnesses possibly related to counterfeit botulinum toxin reported in Illinois and Tennessee, prompted the American Society for Dermatologic Surgery Association (ASDSA) to call on states to increase oversight of medical care in all settings, including medical spas, the ASDSA announced on April 12.

[embed:render:related:node:267216]

The CDC summary advises clinicians to consider the possibility of adverse effects from botulinum toxin injection, including for cosmetic reasons, when patients present with signs and symptoms consistent with botulism near the injection site. Symptoms of botulism include blurry or double vision, drooping eyelids, difficulty swallowing, difficulty breathing, and muscle weakness.

For people who are considering botulinum toxin for cosmetic or medical reasons, recommendations from the CDC include asking the provider and setting, such as a clinic or spa, if they are licensed and trained to provide these injections, and to ask if the product is approved by the FDA and from a reliable source, and, “if in doubt, don’t get the injection.”

This ‘Should Never Happen’

“The report of people getting botulism from botulinum toxin injections is frightening, and should never happen,” Lawrence J. Green, MD, clinical professor of dermatology, George Washington University, Washington, told this news organization.

Green_Lawrence_J_MD_web.jpg

These reports show “how important it is to receive botulinum toxin injections only in a medical office, and from or under the direction of a qualified, trained, and licensed individual, like a board certified dermatologist,” added Dr. Green, who practices in Rockville, Maryland. “Other types of practitioners may not adhere to the same standards of professionalism, especially not always putting patient safety first.”

Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.
 

For cases of suspected systemic botulism, the CDC recommends calling the local or state health department for consultation and antitoxin release (as well as information on reporting adverse events). Alternatively, the 24/7 phone number for the CDC clinical botulism service is 770-488-7100.

At least 19 people from nine states have reported serious reactions after receiving botulinum toxin injections from unlicensed or untrained individuals or in non-healthcare settings, such as homes and spas, according to an announcement of an investigation into these reports from the Centers for Disease Control and Prevention posted online April 15.

Reactions have included blurry vision, double vision, drooping eyelids, difficult swallowing or breathing, and other symptoms of botulism.

Of the 19 individuals — all of whom identified as female and had a mean age of 39 years — 9 (60%) were hospitalized and 4 (21%) were treated with botulism antitoxin because of concerns that the botulinum toxin could have spread beyond the injection site. Also, five were tested for botulism and their results were negative.

The CDC, several state and local health departments, and the US Food and Drug Administration (FDA) are investigating these reports, according to the announcement.

CDC_icon_web.jpg

States reporting these cases include Colorado, Florida, Illinois, Kentucky, Nebraska, New Jersey, New York, Tennessee, and Washington. According to the CDC summary, some of the individuals “received injections with counterfeit products or products with unverified sources. Investigation into the sources of these products is ongoing.” All but one report involved receiving botulinum toxin injections for cosmetic purposes.

Recent cases of botulism-like illnesses possibly related to counterfeit botulinum toxin reported in Illinois and Tennessee, prompted the American Society for Dermatologic Surgery Association (ASDSA) to call on states to increase oversight of medical care in all settings, including medical spas, the ASDSA announced on April 12.

[embed:render:related:node:267216]

The CDC summary advises clinicians to consider the possibility of adverse effects from botulinum toxin injection, including for cosmetic reasons, when patients present with signs and symptoms consistent with botulism near the injection site. Symptoms of botulism include blurry or double vision, drooping eyelids, difficulty swallowing, difficulty breathing, and muscle weakness.

For people who are considering botulinum toxin for cosmetic or medical reasons, recommendations from the CDC include asking the provider and setting, such as a clinic or spa, if they are licensed and trained to provide these injections, and to ask if the product is approved by the FDA and from a reliable source, and, “if in doubt, don’t get the injection.”

This ‘Should Never Happen’

“The report of people getting botulism from botulinum toxin injections is frightening, and should never happen,” Lawrence J. Green, MD, clinical professor of dermatology, George Washington University, Washington, told this news organization.

Green_Lawrence_J_MD_web.jpg

These reports show “how important it is to receive botulinum toxin injections only in a medical office, and from or under the direction of a qualified, trained, and licensed individual, like a board certified dermatologist,” added Dr. Green, who practices in Rockville, Maryland. “Other types of practitioners may not adhere to the same standards of professionalism, especially not always putting patient safety first.”

Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.
 

For cases of suspected systemic botulism, the CDC recommends calling the local or state health department for consultation and antitoxin release (as well as information on reporting adverse events). Alternatively, the 24/7 phone number for the CDC clinical botulism service is 770-488-7100.

A panel of US government advisers unanimously backed use of highly sensitive tests that check for minimal residual disease (MRD) in efforts to accelerate approvals of drugs for multiple myeloma, an incurable blood cancer.

The Oncologic Drugs Advisory Committee (ODAC) of the US Food and Drug Administration (FDA) voted 12-0 on April 12 on the following question: Does the evidence support the use of MRD as an accelerated approval endpoint in multiple myeloma clinical trials?

The FDA is not bound to accept the recommendations of its panels, but often does so.

ODAC panelists said they felt comfortable in this recommendation because they expected the FDA to mandate confirmatory studies of any drugs to be given accelerated approval based on MRD data.

There’s a risk that MRD results might mislead regulators into clearing a drug later found to lack benefit, said Christopher Hourigan, DM, DPhil, an ODAC panelist and a physician-scientist at Virginia Tech, Blacksburg, Virginia, who treats people with blood cancer. Further tests would ultimately show if drugs cleared based on MRD data actually delivered benefits such as extending progression-free survival (PFS).

“That’s why we’re talking about accelerated approval,” Dr. Hourigan said. “There is harm to inaction. We’re not currently curing people in multiple myeloma. I’m not willing to make patients wait on principle for a theoretical perfect that may never come.”

“Our responsibility is to accept the world as messy and be agile enough to adapt and iterate that the evidence develops rather than create barriers to the work of discovering effective new therapies for these patients,” he added.

Advances in testing now allow for detection of the presence of malignant cells at orders of magnitude below previous assessments. MRD assays used in tracking what’s happening with myeloma generally have a sensitivity level of 10^-5, or a detection capacity of one cell of 100,000, said Ola Landgren, MD, PhD, of the University of Miami, Miami, Florida, during a presentation at the meeting.

The April 12 meeting was somewhat unusual for ODAC.

Instead of reviewing the benefits and risks of a specific drug, the panel reviewed results from two separate major research efforts done to see how MRD could be used in development of drugs.

These were Dr. Landgren’s EVIDENCE (Evaluating minimal residual disease as an intermediate clinical endpoint for multiple myeloma) meta-analysis, and the similar work of the i2TEAMM group, affiliated with the International Myeloma Foundation.

In its review, the FDA staff noted differences in the approaches of the two groups. In its analysis, the i2TEAMM removed information about patients with missing MRD data, while the University of Miami team retained information about these kinds of patients in the analyses and assigned their status to be MRD positive.

The FDA staff also noted in their review and presentations weaknesses in the case for MRD. For example, the FDA staff noted that the treatment effect on MRD negativity was not statistically significant in 4 of the 8 treatment comparisons in the work from Dr. Landgren and colleagues.

The FDA staff looked at what these analyses suggested at both an individual level and trial level. The data from these two research projects taken as a whole showed “strong individual-level” associations between negative MRD findings and later positive outcomes for patients, although trial-level associations were “weak to moderate” in some cases, the staff wrote.

The FDA staff concluded that the research appeared to support arguments in favor of the “prognostic value,” even with outstanding questions about how best to use this test.

In the briefing document for the meeting, the FDA also emphasized the need for new treatments.

Multiple myeloma remains an incurable disease with a 5-year relative survival rate of 59.8%, even after significant recent progress in treatment, the agency said. In the past decade, the FDA has approved 15 new drugs and greater than 20 new indications have been approved for the treatment of patients with multiple myeloma.

The FDA has been working with drugmakers and academic researchers for several years to address the potential of MRD in development of blood cancers. The agency in 2020 issued a guidance document on this issue.

Several ODAC members praised the i2TEAMM and Dr. Landgren’s EVIDENCE teams for their work, which took place across several nations and extended over many years.

“This was a herculean effort. It really changes the playbook for how we think about biomarkers across all cancer types,” said ODAC panelist Neil Vasan, MD, PhD, of Columbia University, New York, NY. “To me, the important word was reasonable. Is this a reasonable surrogate endpoint? Is this a reasonable intermediate endpoint? I think it is more than reasonable.”

Still, ODAC panelist Jorge Nieva, MD, raised a point of concern about how use of MRD as an endpoint could change the design of studies. He urged caution among researchers about potential ramping up of collection of MRD tests in search of more robust data, which could lead to more testing for patients.

“I have this tremendous fear that this is going to mean every myeloma protocol has a marrow biopsy every six weeks on the patients forever,” said Dr. Nieva of the Keck School of Medicine, University of Southern California, Los Angeles. “I just don’t want to see that happen. So I think we need to balance these two things.”

A panel of US government advisers unanimously backed use of highly sensitive tests that check for minimal residual disease (MRD) in efforts to accelerate approvals of drugs for multiple myeloma, an incurable blood cancer.

The Oncologic Drugs Advisory Committee (ODAC) of the US Food and Drug Administration (FDA) voted 12-0 on April 12 on the following question: Does the evidence support the use of MRD as an accelerated approval endpoint in multiple myeloma clinical trials?

The FDA is not bound to accept the recommendations of its panels, but often does so.

ODAC panelists said they felt comfortable in this recommendation because they expected the FDA to mandate confirmatory studies of any drugs to be given accelerated approval based on MRD data.

There’s a risk that MRD results might mislead regulators into clearing a drug later found to lack benefit, said Christopher Hourigan, DM, DPhil, an ODAC panelist and a physician-scientist at Virginia Tech, Blacksburg, Virginia, who treats people with blood cancer. Further tests would ultimately show if drugs cleared based on MRD data actually delivered benefits such as extending progression-free survival (PFS).

“That’s why we’re talking about accelerated approval,” Dr. Hourigan said. “There is harm to inaction. We’re not currently curing people in multiple myeloma. I’m not willing to make patients wait on principle for a theoretical perfect that may never come.”

“Our responsibility is to accept the world as messy and be agile enough to adapt and iterate that the evidence develops rather than create barriers to the work of discovering effective new therapies for these patients,” he added.

Advances in testing now allow for detection of the presence of malignant cells at orders of magnitude below previous assessments. MRD assays used in tracking what’s happening with myeloma generally have a sensitivity level of 10^-5, or a detection capacity of one cell of 100,000, said Ola Landgren, MD, PhD, of the University of Miami, Miami, Florida, during a presentation at the meeting.

The April 12 meeting was somewhat unusual for ODAC.

Instead of reviewing the benefits and risks of a specific drug, the panel reviewed results from two separate major research efforts done to see how MRD could be used in development of drugs.

These were Dr. Landgren’s EVIDENCE (Evaluating minimal residual disease as an intermediate clinical endpoint for multiple myeloma) meta-analysis, and the similar work of the i2TEAMM group, affiliated with the International Myeloma Foundation.

In its review, the FDA staff noted differences in the approaches of the two groups. In its analysis, the i2TEAMM removed information about patients with missing MRD data, while the University of Miami team retained information about these kinds of patients in the analyses and assigned their status to be MRD positive.

The FDA staff also noted in their review and presentations weaknesses in the case for MRD. For example, the FDA staff noted that the treatment effect on MRD negativity was not statistically significant in 4 of the 8 treatment comparisons in the work from Dr. Landgren and colleagues.

The FDA staff looked at what these analyses suggested at both an individual level and trial level. The data from these two research projects taken as a whole showed “strong individual-level” associations between negative MRD findings and later positive outcomes for patients, although trial-level associations were “weak to moderate” in some cases, the staff wrote.

The FDA staff concluded that the research appeared to support arguments in favor of the “prognostic value,” even with outstanding questions about how best to use this test.

In the briefing document for the meeting, the FDA also emphasized the need for new treatments.

Multiple myeloma remains an incurable disease with a 5-year relative survival rate of 59.8%, even after significant recent progress in treatment, the agency said. In the past decade, the FDA has approved 15 new drugs and greater than 20 new indications have been approved for the treatment of patients with multiple myeloma.

The FDA has been working with drugmakers and academic researchers for several years to address the potential of MRD in development of blood cancers. The agency in 2020 issued a guidance document on this issue.

Several ODAC members praised the i2TEAMM and Dr. Landgren’s EVIDENCE teams for their work, which took place across several nations and extended over many years.

“This was a herculean effort. It really changes the playbook for how we think about biomarkers across all cancer types,” said ODAC panelist Neil Vasan, MD, PhD, of Columbia University, New York, NY. “To me, the important word was reasonable. Is this a reasonable surrogate endpoint? Is this a reasonable intermediate endpoint? I think it is more than reasonable.”

Still, ODAC panelist Jorge Nieva, MD, raised a point of concern about how use of MRD as an endpoint could change the design of studies. He urged caution among researchers about potential ramping up of collection of MRD tests in search of more robust data, which could lead to more testing for patients.

“I have this tremendous fear that this is going to mean every myeloma protocol has a marrow biopsy every six weeks on the patients forever,” said Dr. Nieva of the Keck School of Medicine, University of Southern California, Los Angeles. “I just don’t want to see that happen. So I think we need to balance these two things.”

A panel of US government advisers unanimously backed use of highly sensitive tests that check for minimal residual disease (MRD) in efforts to accelerate approvals of drugs for multiple myeloma, an incurable blood cancer.

The Oncologic Drugs Advisory Committee (ODAC) of the US Food and Drug Administration (FDA) voted 12-0 on April 12 on the following question: Does the evidence support the use of MRD as an accelerated approval endpoint in multiple myeloma clinical trials?

The FDA is not bound to accept the recommendations of its panels, but often does so.

ODAC panelists said they felt comfortable in this recommendation because they expected the FDA to mandate confirmatory studies of any drugs to be given accelerated approval based on MRD data.

There’s a risk that MRD results might mislead regulators into clearing a drug later found to lack benefit, said Christopher Hourigan, DM, DPhil, an ODAC panelist and a physician-scientist at Virginia Tech, Blacksburg, Virginia, who treats people with blood cancer. Further tests would ultimately show if drugs cleared based on MRD data actually delivered benefits such as extending progression-free survival (PFS).

“That’s why we’re talking about accelerated approval,” Dr. Hourigan said. “There is harm to inaction. We’re not currently curing people in multiple myeloma. I’m not willing to make patients wait on principle for a theoretical perfect that may never come.”

“Our responsibility is to accept the world as messy and be agile enough to adapt and iterate that the evidence develops rather than create barriers to the work of discovering effective new therapies for these patients,” he added.

Advances in testing now allow for detection of the presence of malignant cells at orders of magnitude below previous assessments. MRD assays used in tracking what’s happening with myeloma generally have a sensitivity level of 10^-5, or a detection capacity of one cell of 100,000, said Ola Landgren, MD, PhD, of the University of Miami, Miami, Florida, during a presentation at the meeting.

The April 12 meeting was somewhat unusual for ODAC.

Instead of reviewing the benefits and risks of a specific drug, the panel reviewed results from two separate major research efforts done to see how MRD could be used in development of drugs.

These were Dr. Landgren’s EVIDENCE (Evaluating minimal residual disease as an intermediate clinical endpoint for multiple myeloma) meta-analysis, and the similar work of the i2TEAMM group, affiliated with the International Myeloma Foundation.

In its review, the FDA staff noted differences in the approaches of the two groups. In its analysis, the i2TEAMM removed information about patients with missing MRD data, while the University of Miami team retained information about these kinds of patients in the analyses and assigned their status to be MRD positive.

The FDA staff also noted in their review and presentations weaknesses in the case for MRD. For example, the FDA staff noted that the treatment effect on MRD negativity was not statistically significant in 4 of the 8 treatment comparisons in the work from Dr. Landgren and colleagues.

The FDA staff looked at what these analyses suggested at both an individual level and trial level. The data from these two research projects taken as a whole showed “strong individual-level” associations between negative MRD findings and later positive outcomes for patients, although trial-level associations were “weak to moderate” in some cases, the staff wrote.

The FDA staff concluded that the research appeared to support arguments in favor of the “prognostic value,” even with outstanding questions about how best to use this test.

In the briefing document for the meeting, the FDA also emphasized the need for new treatments.

Multiple myeloma remains an incurable disease with a 5-year relative survival rate of 59.8%, even after significant recent progress in treatment, the agency said. In the past decade, the FDA has approved 15 new drugs and greater than 20 new indications have been approved for the treatment of patients with multiple myeloma.

The FDA has been working with drugmakers and academic researchers for several years to address the potential of MRD in development of blood cancers. The agency in 2020 issued a guidance document on this issue.

Several ODAC members praised the i2TEAMM and Dr. Landgren’s EVIDENCE teams for their work, which took place across several nations and extended over many years.

“This was a herculean effort. It really changes the playbook for how we think about biomarkers across all cancer types,” said ODAC panelist Neil Vasan, MD, PhD, of Columbia University, New York, NY. “To me, the important word was reasonable. Is this a reasonable surrogate endpoint? Is this a reasonable intermediate endpoint? I think it is more than reasonable.”

Still, ODAC panelist Jorge Nieva, MD, raised a point of concern about how use of MRD as an endpoint could change the design of studies. He urged caution among researchers about potential ramping up of collection of MRD tests in search of more robust data, which could lead to more testing for patients.

“I have this tremendous fear that this is going to mean every myeloma protocol has a marrow biopsy every six weeks on the patients forever,” said Dr. Nieva of the Keck School of Medicine, University of Southern California, Los Angeles. “I just don’t want to see that happen. So I think we need to balance these two things.”

On April 4, 2024, the US Food and Drug Administration (FDA) accepted a supplemental Biologics License Application (sBLA) to review bimekizumab-bkzx, an interleukin (IL)-17A and IL-17F inhibitor, for the treatment of adults with moderate to severe hidradenitis suppurativa (HS).

The agency also accepted a second sBLA for a bimekizumab-bkzx 2-mL device.

The developments were announced in a press release from UCB, the manufacturer of bimekizumab-bkzx (Bimzelx), which was first approved in the United States in October 2023 for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

[embed:render:related:node:268365]

According to the press release, acceptance of the sBLA was based on results from two phase 3 studies known as BE HEARD I and BE HEARD II, which found that bimekizumab-bkzx showed clinically meaningful improvements compared with placebo at week 16 and were sustained to week 48. If approved, this would be the first HS approval for bimekizumab-bkzx worldwide. In the European Union, it is approved for treating adults with psoriatic arthritis and axial spondyloarthritis, in addition to moderate to severe psoriasis.

According to the company, approval of the 2-mL injection device would mean that patients would have an alternative one-injection regimen option; currently, one dose for psoriasis is administered as two 1-mL injections. Full US prescribing information for bimekizumab-bkzx can be found here.

A version of this article first appeared on Medscape.com.

On April 4, 2024, the US Food and Drug Administration (FDA) accepted a supplemental Biologics License Application (sBLA) to review bimekizumab-bkzx, an interleukin (IL)-17A and IL-17F inhibitor, for the treatment of adults with moderate to severe hidradenitis suppurativa (HS).

The agency also accepted a second sBLA for a bimekizumab-bkzx 2-mL device.

The developments were announced in a press release from UCB, the manufacturer of bimekizumab-bkzx (Bimzelx), which was first approved in the United States in October 2023 for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

[embed:render:related:node:268365]

According to the press release, acceptance of the sBLA was based on results from two phase 3 studies known as BE HEARD I and BE HEARD II, which found that bimekizumab-bkzx showed clinically meaningful improvements compared with placebo at week 16 and were sustained to week 48. If approved, this would be the first HS approval for bimekizumab-bkzx worldwide. In the European Union, it is approved for treating adults with psoriatic arthritis and axial spondyloarthritis, in addition to moderate to severe psoriasis.

According to the company, approval of the 2-mL injection device would mean that patients would have an alternative one-injection regimen option; currently, one dose for psoriasis is administered as two 1-mL injections. Full US prescribing information for bimekizumab-bkzx can be found here.

A version of this article first appeared on Medscape.com.

On April 4, 2024, the US Food and Drug Administration (FDA) accepted a supplemental Biologics License Application (sBLA) to review bimekizumab-bkzx, an interleukin (IL)-17A and IL-17F inhibitor, for the treatment of adults with moderate to severe hidradenitis suppurativa (HS).

The agency also accepted a second sBLA for a bimekizumab-bkzx 2-mL device.

The developments were announced in a press release from UCB, the manufacturer of bimekizumab-bkzx (Bimzelx), which was first approved in the United States in October 2023 for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

[embed:render:related:node:268365]

According to the press release, acceptance of the sBLA was based on results from two phase 3 studies known as BE HEARD I and BE HEARD II, which found that bimekizumab-bkzx showed clinically meaningful improvements compared with placebo at week 16 and were sustained to week 48. If approved, this would be the first HS approval for bimekizumab-bkzx worldwide. In the European Union, it is approved for treating adults with psoriatic arthritis and axial spondyloarthritis, in addition to moderate to severe psoriasis.

According to the company, approval of the 2-mL injection device would mean that patients would have an alternative one-injection regimen option; currently, one dose for psoriasis is administered as two 1-mL injections. Full US prescribing information for bimekizumab-bkzx can be found here.

A version of this article first appeared on Medscape.com.