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FDA grants rezafungin QIDP and fast track designations
The U.S. Food and Drug Administration (FDA) has granted Qualified Infectious Disease Product (QIDP) and fast track designations for rezafungin, an injection for the prevention of invasive fungal infections in adults undergoing allogeneic bone marrow transplantation.
Rezafungin is a novel antifungal echinocandin being developed by Cidara Therapeutics to treat candidemia and invasive candidiasis and for prophylaxis of invasive fungal infections due to Candida, Aspergillus, and Pneumocystis.
These pathogens typically affect patients with compromised immune systems, such as patients undergoing organ, bone marrow transplants, or chemotherapy.
Rezafungin is administered as a once-weekly, high-exposure therapy. According to Cidara, no one agent is approved to prevent infections caused by these pathogens. Current prophylaxis regimens often require multiple antifungal drugs, causing safety and tolerability issues.
The QIDP designation offers incentives for the development of new antifungal and antibacterial drugs, including fast track, priority review and, if approved by the FDA, eligibility for an additional five years of marketing exclusivity.
Fast track designation enables more frequent interactions with the FDA review team to expedite drug development.
For QIDP designation, a drug candidate must treat serious or life-threatening infections, particularly those caused by bacteria and fungi resistant to treatment or by resistant pathogens identified by the FDA.
Rezafungin acetate, formerly known as CD101 IV, met its primary safety and efficacy objectives in the phase 2 STRIVE trial, providing support for the company to initiate phase 3 trials.
The phase 2 trial compared rezafungin to caspofungin in patients with candidemia and/or invasive candidiasis.
Investigators enrolled 92 patients in the microbial intent-to-treat population.
Patients were randomized to one of two dose groups of rezafungin or to the caspofungin arm.
One hundred percent of patients with invasive candidiasis responded to the rezafungin 400 mg first-week dose followed by 200 mg once weekly up to four weeks, compared to 33% of patients who responded to daily caspofungin.
The company reported no concerning adverse event trends.
Cidara is initiating phase 3 pivotal trials of rezafungin in the treatment of candidemia and invasive candidiasis and the prophylaxis of invasive fungal infections.
The U.S. Food and Drug Administration (FDA) has granted Qualified Infectious Disease Product (QIDP) and fast track designations for rezafungin, an injection for the prevention of invasive fungal infections in adults undergoing allogeneic bone marrow transplantation.
Rezafungin is a novel antifungal echinocandin being developed by Cidara Therapeutics to treat candidemia and invasive candidiasis and for prophylaxis of invasive fungal infections due to Candida, Aspergillus, and Pneumocystis.
These pathogens typically affect patients with compromised immune systems, such as patients undergoing organ, bone marrow transplants, or chemotherapy.
Rezafungin is administered as a once-weekly, high-exposure therapy. According to Cidara, no one agent is approved to prevent infections caused by these pathogens. Current prophylaxis regimens often require multiple antifungal drugs, causing safety and tolerability issues.
The QIDP designation offers incentives for the development of new antifungal and antibacterial drugs, including fast track, priority review and, if approved by the FDA, eligibility for an additional five years of marketing exclusivity.
Fast track designation enables more frequent interactions with the FDA review team to expedite drug development.
For QIDP designation, a drug candidate must treat serious or life-threatening infections, particularly those caused by bacteria and fungi resistant to treatment or by resistant pathogens identified by the FDA.
Rezafungin acetate, formerly known as CD101 IV, met its primary safety and efficacy objectives in the phase 2 STRIVE trial, providing support for the company to initiate phase 3 trials.
The phase 2 trial compared rezafungin to caspofungin in patients with candidemia and/or invasive candidiasis.
Investigators enrolled 92 patients in the microbial intent-to-treat population.
Patients were randomized to one of two dose groups of rezafungin or to the caspofungin arm.
One hundred percent of patients with invasive candidiasis responded to the rezafungin 400 mg first-week dose followed by 200 mg once weekly up to four weeks, compared to 33% of patients who responded to daily caspofungin.
The company reported no concerning adverse event trends.
Cidara is initiating phase 3 pivotal trials of rezafungin in the treatment of candidemia and invasive candidiasis and the prophylaxis of invasive fungal infections.
The U.S. Food and Drug Administration (FDA) has granted Qualified Infectious Disease Product (QIDP) and fast track designations for rezafungin, an injection for the prevention of invasive fungal infections in adults undergoing allogeneic bone marrow transplantation.
Rezafungin is a novel antifungal echinocandin being developed by Cidara Therapeutics to treat candidemia and invasive candidiasis and for prophylaxis of invasive fungal infections due to Candida, Aspergillus, and Pneumocystis.
These pathogens typically affect patients with compromised immune systems, such as patients undergoing organ, bone marrow transplants, or chemotherapy.
Rezafungin is administered as a once-weekly, high-exposure therapy. According to Cidara, no one agent is approved to prevent infections caused by these pathogens. Current prophylaxis regimens often require multiple antifungal drugs, causing safety and tolerability issues.
The QIDP designation offers incentives for the development of new antifungal and antibacterial drugs, including fast track, priority review and, if approved by the FDA, eligibility for an additional five years of marketing exclusivity.
Fast track designation enables more frequent interactions with the FDA review team to expedite drug development.
For QIDP designation, a drug candidate must treat serious or life-threatening infections, particularly those caused by bacteria and fungi resistant to treatment or by resistant pathogens identified by the FDA.
Rezafungin acetate, formerly known as CD101 IV, met its primary safety and efficacy objectives in the phase 2 STRIVE trial, providing support for the company to initiate phase 3 trials.
The phase 2 trial compared rezafungin to caspofungin in patients with candidemia and/or invasive candidiasis.
Investigators enrolled 92 patients in the microbial intent-to-treat population.
Patients were randomized to one of two dose groups of rezafungin or to the caspofungin arm.
One hundred percent of patients with invasive candidiasis responded to the rezafungin 400 mg first-week dose followed by 200 mg once weekly up to four weeks, compared to 33% of patients who responded to daily caspofungin.
The company reported no concerning adverse event trends.
Cidara is initiating phase 3 pivotal trials of rezafungin in the treatment of candidemia and invasive candidiasis and the prophylaxis of invasive fungal infections.
Factors that may drive relapse in AYAs with ALL
New research suggests race, clinical trial participation, and treatment duration may influence the risk of relapse in adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL).
The study showed that AYAs with ALL were significantly more likely to relapse than pediatric ALL patients.
Among AYAs, the risk of on-therapy relapse was higher for non-white patients and those who did not participate in clinical trials. The risk of relapse after therapy was higher for AYAs with a shorter treatment duration.
Julie A. Wolfson, MD, of University of Alabama at Birmingham, and her colleagues reported these findings in Cancer Epidemiology, Biomarkers & Prevention.
The researchers conducted this study to investigate why AYAs with ALL have not experienced the same improvement in survival rates as pediatric patients with ALL.
“Patients diagnosed between the ages of 15 and 39 simply have not seen the same improvement as those in other age groups,” Dr. Wolfson said. “In this study, we examined factors related to health care delivery and treatment to increase our understanding of why they experience poorer outcomes.”
The researchers retrospectively studied ALL patients diagnosed between ages 1 and 39 and treated at a single center between 1990 and 2010.
Ninety-one patients were children (ages 1 to 14), and 93 were AYAs (ages 15 to 39).
The researchers assessed variables including demographics, insurance status, participation in clinical trials, duration of treatment, and whether the patients had been treated with pediatric-inspired or adult-inspired regimens. Using Kaplan-Meier survival analysis, the researchers calculated the risk of relapse.
Results
As previous research indicated, children with ALL had superior relapse-free survival compared to AYAs.
The 5-year relapse-free survival rate was 74% in children, 29% in younger AYAs (ages 15 to 21), and 32% in older AYAs (ages 22-39). The difference between children and AYAs was statistically significant (P<0.0001), but the difference between younger and older AYAs was not (P=0.6).
Forty-eight percent of AYAs relapsed while on therapy, compared with 17% of children (P<0.001).
In a multivariable analysis adjusted for clinical prognosticators, health care delivery, and treatment, the risk of on-therapy relapse was more than 10 times higher among AYAs than children (hazard ratio [HR], 10.5; P=0.004).
Among AYAs, the strongest predictors of on-therapy relapse were race and enrollment in clinical trials.
Non-white patients were more than twice as likely to relapse as white patients (HR, 2.2; P=0.05), and patients who were not enrolled in clinical trials were more than twice as likely to relapse as trial participants (HR, 2.6, P=0.04).
Dr. Wolfson said this finding adds to evidence suggesting AYA patients should be encouraged to participate in clinical trials.
“It is possible that patients sometimes benefit from being enrolled on a clinical trial not only because the therapy itself is providing a benefit, but also because it is a protocolized, regulated approach that requires patients to stay on course and not take breaks,” she said.
After the completion of therapy, 47% of AYAs suffered a relapse, compared to 13% of children (P<0.0001).
In a multivariable analysis, the risk of relapse after therapy was more than seven times higher among AYAs than children (HR, 7.7; P<0.001).
Among AYAs who relapsed after therapy, the most significant factor associated with relapse was the duration of treatment.
For each additional month of consolidation therapy, there was a 20% lower risk of relapse (HR, 0.8; P=0.03). And for each additional month of maintenance, there was a 30% lower risk of relapse (HR, 0.7; P<0.001).
Dr. Wolfson noted that a range of factors may affect the duration of treatment. For example, the AYA population is more likely to be uninsured or underinsured, which can make them more likely to stop treatment or miss appointments.
Finally, Dr. Wolfson acknowledged that this study had limitations, primarily its single-institution approach and its limited sample size.
This study was funded by the National Institutes of Health, the St. Baldrick’s Scholar Career Development Award, and the Concern Foundation. The authors declared no conflicts of interest.
New research suggests race, clinical trial participation, and treatment duration may influence the risk of relapse in adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL).
The study showed that AYAs with ALL were significantly more likely to relapse than pediatric ALL patients.
Among AYAs, the risk of on-therapy relapse was higher for non-white patients and those who did not participate in clinical trials. The risk of relapse after therapy was higher for AYAs with a shorter treatment duration.
Julie A. Wolfson, MD, of University of Alabama at Birmingham, and her colleagues reported these findings in Cancer Epidemiology, Biomarkers & Prevention.
The researchers conducted this study to investigate why AYAs with ALL have not experienced the same improvement in survival rates as pediatric patients with ALL.
“Patients diagnosed between the ages of 15 and 39 simply have not seen the same improvement as those in other age groups,” Dr. Wolfson said. “In this study, we examined factors related to health care delivery and treatment to increase our understanding of why they experience poorer outcomes.”
The researchers retrospectively studied ALL patients diagnosed between ages 1 and 39 and treated at a single center between 1990 and 2010.
Ninety-one patients were children (ages 1 to 14), and 93 were AYAs (ages 15 to 39).
The researchers assessed variables including demographics, insurance status, participation in clinical trials, duration of treatment, and whether the patients had been treated with pediatric-inspired or adult-inspired regimens. Using Kaplan-Meier survival analysis, the researchers calculated the risk of relapse.
Results
As previous research indicated, children with ALL had superior relapse-free survival compared to AYAs.
The 5-year relapse-free survival rate was 74% in children, 29% in younger AYAs (ages 15 to 21), and 32% in older AYAs (ages 22-39). The difference between children and AYAs was statistically significant (P<0.0001), but the difference between younger and older AYAs was not (P=0.6).
Forty-eight percent of AYAs relapsed while on therapy, compared with 17% of children (P<0.001).
In a multivariable analysis adjusted for clinical prognosticators, health care delivery, and treatment, the risk of on-therapy relapse was more than 10 times higher among AYAs than children (hazard ratio [HR], 10.5; P=0.004).
Among AYAs, the strongest predictors of on-therapy relapse were race and enrollment in clinical trials.
Non-white patients were more than twice as likely to relapse as white patients (HR, 2.2; P=0.05), and patients who were not enrolled in clinical trials were more than twice as likely to relapse as trial participants (HR, 2.6, P=0.04).
Dr. Wolfson said this finding adds to evidence suggesting AYA patients should be encouraged to participate in clinical trials.
“It is possible that patients sometimes benefit from being enrolled on a clinical trial not only because the therapy itself is providing a benefit, but also because it is a protocolized, regulated approach that requires patients to stay on course and not take breaks,” she said.
After the completion of therapy, 47% of AYAs suffered a relapse, compared to 13% of children (P<0.0001).
In a multivariable analysis, the risk of relapse after therapy was more than seven times higher among AYAs than children (HR, 7.7; P<0.001).
Among AYAs who relapsed after therapy, the most significant factor associated with relapse was the duration of treatment.
For each additional month of consolidation therapy, there was a 20% lower risk of relapse (HR, 0.8; P=0.03). And for each additional month of maintenance, there was a 30% lower risk of relapse (HR, 0.7; P<0.001).
Dr. Wolfson noted that a range of factors may affect the duration of treatment. For example, the AYA population is more likely to be uninsured or underinsured, which can make them more likely to stop treatment or miss appointments.
Finally, Dr. Wolfson acknowledged that this study had limitations, primarily its single-institution approach and its limited sample size.
This study was funded by the National Institutes of Health, the St. Baldrick’s Scholar Career Development Award, and the Concern Foundation. The authors declared no conflicts of interest.
New research suggests race, clinical trial participation, and treatment duration may influence the risk of relapse in adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL).
The study showed that AYAs with ALL were significantly more likely to relapse than pediatric ALL patients.
Among AYAs, the risk of on-therapy relapse was higher for non-white patients and those who did not participate in clinical trials. The risk of relapse after therapy was higher for AYAs with a shorter treatment duration.
Julie A. Wolfson, MD, of University of Alabama at Birmingham, and her colleagues reported these findings in Cancer Epidemiology, Biomarkers & Prevention.
The researchers conducted this study to investigate why AYAs with ALL have not experienced the same improvement in survival rates as pediatric patients with ALL.
“Patients diagnosed between the ages of 15 and 39 simply have not seen the same improvement as those in other age groups,” Dr. Wolfson said. “In this study, we examined factors related to health care delivery and treatment to increase our understanding of why they experience poorer outcomes.”
The researchers retrospectively studied ALL patients diagnosed between ages 1 and 39 and treated at a single center between 1990 and 2010.
Ninety-one patients were children (ages 1 to 14), and 93 were AYAs (ages 15 to 39).
The researchers assessed variables including demographics, insurance status, participation in clinical trials, duration of treatment, and whether the patients had been treated with pediatric-inspired or adult-inspired regimens. Using Kaplan-Meier survival analysis, the researchers calculated the risk of relapse.
Results
As previous research indicated, children with ALL had superior relapse-free survival compared to AYAs.
The 5-year relapse-free survival rate was 74% in children, 29% in younger AYAs (ages 15 to 21), and 32% in older AYAs (ages 22-39). The difference between children and AYAs was statistically significant (P<0.0001), but the difference between younger and older AYAs was not (P=0.6).
Forty-eight percent of AYAs relapsed while on therapy, compared with 17% of children (P<0.001).
In a multivariable analysis adjusted for clinical prognosticators, health care delivery, and treatment, the risk of on-therapy relapse was more than 10 times higher among AYAs than children (hazard ratio [HR], 10.5; P=0.004).
Among AYAs, the strongest predictors of on-therapy relapse were race and enrollment in clinical trials.
Non-white patients were more than twice as likely to relapse as white patients (HR, 2.2; P=0.05), and patients who were not enrolled in clinical trials were more than twice as likely to relapse as trial participants (HR, 2.6, P=0.04).
Dr. Wolfson said this finding adds to evidence suggesting AYA patients should be encouraged to participate in clinical trials.
“It is possible that patients sometimes benefit from being enrolled on a clinical trial not only because the therapy itself is providing a benefit, but also because it is a protocolized, regulated approach that requires patients to stay on course and not take breaks,” she said.
After the completion of therapy, 47% of AYAs suffered a relapse, compared to 13% of children (P<0.0001).
In a multivariable analysis, the risk of relapse after therapy was more than seven times higher among AYAs than children (HR, 7.7; P<0.001).
Among AYAs who relapsed after therapy, the most significant factor associated with relapse was the duration of treatment.
For each additional month of consolidation therapy, there was a 20% lower risk of relapse (HR, 0.8; P=0.03). And for each additional month of maintenance, there was a 30% lower risk of relapse (HR, 0.7; P<0.001).
Dr. Wolfson noted that a range of factors may affect the duration of treatment. For example, the AYA population is more likely to be uninsured or underinsured, which can make them more likely to stop treatment or miss appointments.
Finally, Dr. Wolfson acknowledged that this study had limitations, primarily its single-institution approach and its limited sample size.
This study was funded by the National Institutes of Health, the St. Baldrick’s Scholar Career Development Award, and the Concern Foundation. The authors declared no conflicts of interest.
Study supports immediate compression after DVT
Immediate compression therapy provides a “clear benefit” for patients with deep vein thrombosis (DVT), according to the senior author of a study published in Blood.
In this prospective study, patients who started compression therapy within the first 24 hours of DVT diagnosis were 20% less likely to develop residual vein occlusion (RVO) than patients who did not start compression therapy in the acute phase.
Furthermore, patients who did not develop RVO were 8% less likely to have post-thrombotic syndrome (PTS) than patients with RVO.
“We found little reason for those treating DVT not to use compression therapy as a prevention measure against future complications,” said study author Arina J. ten Cate-Hoek, MD, PhD, of Maastricht University in the Netherlands.
“Although the use of compression stockings after DVT is routine across much of Europe, it is less common in the United States, where guidelines emphasize compression primarily for patients who complain of ongoing symptoms.”
Dr. ten Cate-Hoek and her colleagues studied 592 adults with DVT who were treated in 10 centers across the Netherlands.
All patients were treated with anticoagulants, largely vitamin K antagonists (80.6%) but also direct oral anticoagulants (3.0%), investigational anticoagulants (11.1%), and low-molecular-weight heparin (4.4%).
Within 24 hours of DVT diagnosis, most patients received compression therapy (pressure 35 mmHg) with either multilayer compression bandaging (62.3%) or compression hosiery (25.5%). A minority of patients did not receive compression in the acute phase (12.2%).
The average time from DVT diagnosis to RVO assessment was 5.3 months.
The incidence of RVO was significantly lower in patients who received immediate compression than in those who did not—46.3% and 66.7%, respectively (odds ratio [OR], 0.46; P=0.005).
In addition, PTS was more common among patients with RVO.
At 6 months, the incidence of PTS was 55.7% among patients with RVO and 44.3% among patients without RVO (OR, 0.66; P=0.029). At 24 months, the incidence of PTS was 54.0% and 46.0%, respectively (OR, 0.65; P=0.013).
The researchers said there was no significant association between RVO and recurrent DVT or pulmonary embolism.
Among the 30 patients with DVT recurrence, 60% had RVO and 40% did not (OR, 0.82; P=0.263).
Among the 19 patients who had recurrent pulmonary embolism, 52.6% had RVO and 47.7% did not (OR, 0.95; P=0.805).
Dr. ten Cate-Hoek noted that compression therapy is thought to improve blood flow by reducing the diameter of veins so that blood is pushed through them more forcefully, which helps to clear clot material.
“I think we can infer from our findings that this improved blood flow certainly helps prevent complications like residual vein occlusion and post-thrombotic syndrome after DVT,” she said.
“Given these outcomes, and that compression stockings are fairly easy to self-administer, relatively inexpensive, and minimally intrusive, compression therapy offers a clear benefit for all patients with DVT.”
Immediate compression therapy provides a “clear benefit” for patients with deep vein thrombosis (DVT), according to the senior author of a study published in Blood.
In this prospective study, patients who started compression therapy within the first 24 hours of DVT diagnosis were 20% less likely to develop residual vein occlusion (RVO) than patients who did not start compression therapy in the acute phase.
Furthermore, patients who did not develop RVO were 8% less likely to have post-thrombotic syndrome (PTS) than patients with RVO.
“We found little reason for those treating DVT not to use compression therapy as a prevention measure against future complications,” said study author Arina J. ten Cate-Hoek, MD, PhD, of Maastricht University in the Netherlands.
“Although the use of compression stockings after DVT is routine across much of Europe, it is less common in the United States, where guidelines emphasize compression primarily for patients who complain of ongoing symptoms.”
Dr. ten Cate-Hoek and her colleagues studied 592 adults with DVT who were treated in 10 centers across the Netherlands.
All patients were treated with anticoagulants, largely vitamin K antagonists (80.6%) but also direct oral anticoagulants (3.0%), investigational anticoagulants (11.1%), and low-molecular-weight heparin (4.4%).
Within 24 hours of DVT diagnosis, most patients received compression therapy (pressure 35 mmHg) with either multilayer compression bandaging (62.3%) or compression hosiery (25.5%). A minority of patients did not receive compression in the acute phase (12.2%).
The average time from DVT diagnosis to RVO assessment was 5.3 months.
The incidence of RVO was significantly lower in patients who received immediate compression than in those who did not—46.3% and 66.7%, respectively (odds ratio [OR], 0.46; P=0.005).
In addition, PTS was more common among patients with RVO.
At 6 months, the incidence of PTS was 55.7% among patients with RVO and 44.3% among patients without RVO (OR, 0.66; P=0.029). At 24 months, the incidence of PTS was 54.0% and 46.0%, respectively (OR, 0.65; P=0.013).
The researchers said there was no significant association between RVO and recurrent DVT or pulmonary embolism.
Among the 30 patients with DVT recurrence, 60% had RVO and 40% did not (OR, 0.82; P=0.263).
Among the 19 patients who had recurrent pulmonary embolism, 52.6% had RVO and 47.7% did not (OR, 0.95; P=0.805).
Dr. ten Cate-Hoek noted that compression therapy is thought to improve blood flow by reducing the diameter of veins so that blood is pushed through them more forcefully, which helps to clear clot material.
“I think we can infer from our findings that this improved blood flow certainly helps prevent complications like residual vein occlusion and post-thrombotic syndrome after DVT,” she said.
“Given these outcomes, and that compression stockings are fairly easy to self-administer, relatively inexpensive, and minimally intrusive, compression therapy offers a clear benefit for all patients with DVT.”
Immediate compression therapy provides a “clear benefit” for patients with deep vein thrombosis (DVT), according to the senior author of a study published in Blood.
In this prospective study, patients who started compression therapy within the first 24 hours of DVT diagnosis were 20% less likely to develop residual vein occlusion (RVO) than patients who did not start compression therapy in the acute phase.
Furthermore, patients who did not develop RVO were 8% less likely to have post-thrombotic syndrome (PTS) than patients with RVO.
“We found little reason for those treating DVT not to use compression therapy as a prevention measure against future complications,” said study author Arina J. ten Cate-Hoek, MD, PhD, of Maastricht University in the Netherlands.
“Although the use of compression stockings after DVT is routine across much of Europe, it is less common in the United States, where guidelines emphasize compression primarily for patients who complain of ongoing symptoms.”
Dr. ten Cate-Hoek and her colleagues studied 592 adults with DVT who were treated in 10 centers across the Netherlands.
All patients were treated with anticoagulants, largely vitamin K antagonists (80.6%) but also direct oral anticoagulants (3.0%), investigational anticoagulants (11.1%), and low-molecular-weight heparin (4.4%).
Within 24 hours of DVT diagnosis, most patients received compression therapy (pressure 35 mmHg) with either multilayer compression bandaging (62.3%) or compression hosiery (25.5%). A minority of patients did not receive compression in the acute phase (12.2%).
The average time from DVT diagnosis to RVO assessment was 5.3 months.
The incidence of RVO was significantly lower in patients who received immediate compression than in those who did not—46.3% and 66.7%, respectively (odds ratio [OR], 0.46; P=0.005).
In addition, PTS was more common among patients with RVO.
At 6 months, the incidence of PTS was 55.7% among patients with RVO and 44.3% among patients without RVO (OR, 0.66; P=0.029). At 24 months, the incidence of PTS was 54.0% and 46.0%, respectively (OR, 0.65; P=0.013).
The researchers said there was no significant association between RVO and recurrent DVT or pulmonary embolism.
Among the 30 patients with DVT recurrence, 60% had RVO and 40% did not (OR, 0.82; P=0.263).
Among the 19 patients who had recurrent pulmonary embolism, 52.6% had RVO and 47.7% did not (OR, 0.95; P=0.805).
Dr. ten Cate-Hoek noted that compression therapy is thought to improve blood flow by reducing the diameter of veins so that blood is pushed through them more forcefully, which helps to clear clot material.
“I think we can infer from our findings that this improved blood flow certainly helps prevent complications like residual vein occlusion and post-thrombotic syndrome after DVT,” she said.
“Given these outcomes, and that compression stockings are fairly easy to self-administer, relatively inexpensive, and minimally intrusive, compression therapy offers a clear benefit for all patients with DVT.”
Placenta-derived product receives orphan designation for HSCT
The U.S. Food and Drug Administration (FDA) has granted orphan designation to PLX-R18 for the treatment of graft failure and incomplete hematopoietic recovery following hematopoietic stem cell transplant (HSCT).
PLX-R18 consists of placenta-derived, mesenchymal-like adherent stromal cells that are designed to be administered to patients without the need for tissue or genetic matching.
PLX-R18 cells release a combination of therapeutic proteins in response to a damaged or poorly functioning hematopoietic system.
PLX-R18 is currently being evaluated for the treatment of insufficient hematopoietic recovery following HSCT in an ongoing, phase 1 trial (NCT03002519).
The trial is designed to evaluate the safety of intramuscular injections of PLX-R18 cells in 24 subjects with incomplete hematopoietic recovery persisting for at least 4 months after HSCT, with a 12-month follow-up period.
The primary endpoint is safety. Exploratory endpoints include changes in platelet and hemoglobin levels, changes in transfusion frequency, a shift from transfusion dependence to transfusion independence, changes in quality of life, and changes in the serum immunological parameters.
PLX-R18 is being developed by Pluristem Therapeutics, Inc. PLX-R18 also has orphan designation for the treatment of acute radiation syndrome.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the United States.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The U.S. Food and Drug Administration (FDA) has granted orphan designation to PLX-R18 for the treatment of graft failure and incomplete hematopoietic recovery following hematopoietic stem cell transplant (HSCT).
PLX-R18 consists of placenta-derived, mesenchymal-like adherent stromal cells that are designed to be administered to patients without the need for tissue or genetic matching.
PLX-R18 cells release a combination of therapeutic proteins in response to a damaged or poorly functioning hematopoietic system.
PLX-R18 is currently being evaluated for the treatment of insufficient hematopoietic recovery following HSCT in an ongoing, phase 1 trial (NCT03002519).
The trial is designed to evaluate the safety of intramuscular injections of PLX-R18 cells in 24 subjects with incomplete hematopoietic recovery persisting for at least 4 months after HSCT, with a 12-month follow-up period.
The primary endpoint is safety. Exploratory endpoints include changes in platelet and hemoglobin levels, changes in transfusion frequency, a shift from transfusion dependence to transfusion independence, changes in quality of life, and changes in the serum immunological parameters.
PLX-R18 is being developed by Pluristem Therapeutics, Inc. PLX-R18 also has orphan designation for the treatment of acute radiation syndrome.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the United States.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The U.S. Food and Drug Administration (FDA) has granted orphan designation to PLX-R18 for the treatment of graft failure and incomplete hematopoietic recovery following hematopoietic stem cell transplant (HSCT).
PLX-R18 consists of placenta-derived, mesenchymal-like adherent stromal cells that are designed to be administered to patients without the need for tissue or genetic matching.
PLX-R18 cells release a combination of therapeutic proteins in response to a damaged or poorly functioning hematopoietic system.
PLX-R18 is currently being evaluated for the treatment of insufficient hematopoietic recovery following HSCT in an ongoing, phase 1 trial (NCT03002519).
The trial is designed to evaluate the safety of intramuscular injections of PLX-R18 cells in 24 subjects with incomplete hematopoietic recovery persisting for at least 4 months after HSCT, with a 12-month follow-up period.
The primary endpoint is safety. Exploratory endpoints include changes in platelet and hemoglobin levels, changes in transfusion frequency, a shift from transfusion dependence to transfusion independence, changes in quality of life, and changes in the serum immunological parameters.
PLX-R18 is being developed by Pluristem Therapeutics, Inc. PLX-R18 also has orphan designation for the treatment of acute radiation syndrome.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the United States.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
FDA lifts partial hold on tazemetostat trials
The U.S. Food and Drug Administration (FDA) has lifted the partial clinical hold on trials of tazemetostat, an EZH2 inhibitor being developed to treat solid tumors and lymphomas.
The FDA had placed the hold in April, and this halted U.S.-based enrollment of new patients in tazemetostat clinical trials.
Now, Epizyme, Inc., the company developing tazemetostat, is in the process of reopening enrollment in all company-sponsored trials in the U.S.
The FDA had placed the partial hold on tazemetostat trials after an adverse event was observed in a pediatric patient on a phase 1 study.
The patient, who had advanced poorly differentiated chordoma, developed secondary T-cell lymphoblastic lymphoma (T-LBL) while taking tazemetostat. The patient has since discontinued tazemetostat and responded to treatment for T-LBL.
“This remains the only case of T-LBL we’ve seen in more than 750 patients treated with tazemetostat,” said Robert Bazemore, president and chief executive officer of Epizyme.
Due to this adverse event and the partial clinical hold, Epizyme began to assess the risk of T-LBL and other secondary malignancies potentially associated with tazemetostat.
The company also assessed the overall risks and benefits of tazemetostat treatment, conducting a review of the published literature and an examination of efficacy and safety data across all of its tazemetostat trials.
Epizyme concluded that the benefits of tazemetostat outweigh the risks, and the risk of T-LBL appears confined to pediatric patients who received higher doses of the drug. The phase 1 pediatric study in which the patient developed T-LBL included higher doses of tazemetostat than those used in the phase 2 adult studies.
Epizyme convened a panel of external scientific and medical experts who reviewed and validated the company’s findings.
“The team at Epizyme has worked diligently in collaboration with external experts and FDA over the past several months, culminating in decisions . . . to lift the partial clinical hold and allow re-opening of enrollment in our clinical trials,” Bazemore said.
He noted that the company is not making any substantial changes to trial designs or the patient populations involved in tazemetostat trials.
However, Epizyme is modifying dosing in the pediatric studies, improving patient monitoring, and making changes to exclusion criteria to reduce the potential risk of T-LBL and other secondary malignancies.
Bazemore said the lifting of the partial clinical hold allows Epizyme to turn its full attention to key priorities, including plans to submit a new drug application for tazemetostat in epithelioid sarcoma.
The company also plans to begin preparing for a potential new drug application for tazemetostat in follicular lymphoma.
Tazemetostat is currently under investigation as monotherapy in phase 2 trials of follicular lymphoma and solid tumor malignancies. The drug is also being studied as part of combination therapy for non-small cell lung cancer and diffuse large B-cell lymphoma (DLBCL).
In August, Epizyme announced its decision to stop developing tazemetostat for use as monotherapy or in combination with prednisolone for patients with DLBCL. However, tazemetostat is still under investigation as a potential treatment for DLBCL as part of other combination regimens.
Now that Epizyme has resolved the U.S. hold on tazemetostat trials, the company is working to resolve partial clinical holds placed in France and Germany to resume trial enrollment in those countries.
The U.S. Food and Drug Administration (FDA) has lifted the partial clinical hold on trials of tazemetostat, an EZH2 inhibitor being developed to treat solid tumors and lymphomas.
The FDA had placed the hold in April, and this halted U.S.-based enrollment of new patients in tazemetostat clinical trials.
Now, Epizyme, Inc., the company developing tazemetostat, is in the process of reopening enrollment in all company-sponsored trials in the U.S.
The FDA had placed the partial hold on tazemetostat trials after an adverse event was observed in a pediatric patient on a phase 1 study.
The patient, who had advanced poorly differentiated chordoma, developed secondary T-cell lymphoblastic lymphoma (T-LBL) while taking tazemetostat. The patient has since discontinued tazemetostat and responded to treatment for T-LBL.
“This remains the only case of T-LBL we’ve seen in more than 750 patients treated with tazemetostat,” said Robert Bazemore, president and chief executive officer of Epizyme.
Due to this adverse event and the partial clinical hold, Epizyme began to assess the risk of T-LBL and other secondary malignancies potentially associated with tazemetostat.
The company also assessed the overall risks and benefits of tazemetostat treatment, conducting a review of the published literature and an examination of efficacy and safety data across all of its tazemetostat trials.
Epizyme concluded that the benefits of tazemetostat outweigh the risks, and the risk of T-LBL appears confined to pediatric patients who received higher doses of the drug. The phase 1 pediatric study in which the patient developed T-LBL included higher doses of tazemetostat than those used in the phase 2 adult studies.
Epizyme convened a panel of external scientific and medical experts who reviewed and validated the company’s findings.
“The team at Epizyme has worked diligently in collaboration with external experts and FDA over the past several months, culminating in decisions . . . to lift the partial clinical hold and allow re-opening of enrollment in our clinical trials,” Bazemore said.
He noted that the company is not making any substantial changes to trial designs or the patient populations involved in tazemetostat trials.
However, Epizyme is modifying dosing in the pediatric studies, improving patient monitoring, and making changes to exclusion criteria to reduce the potential risk of T-LBL and other secondary malignancies.
Bazemore said the lifting of the partial clinical hold allows Epizyme to turn its full attention to key priorities, including plans to submit a new drug application for tazemetostat in epithelioid sarcoma.
The company also plans to begin preparing for a potential new drug application for tazemetostat in follicular lymphoma.
Tazemetostat is currently under investigation as monotherapy in phase 2 trials of follicular lymphoma and solid tumor malignancies. The drug is also being studied as part of combination therapy for non-small cell lung cancer and diffuse large B-cell lymphoma (DLBCL).
In August, Epizyme announced its decision to stop developing tazemetostat for use as monotherapy or in combination with prednisolone for patients with DLBCL. However, tazemetostat is still under investigation as a potential treatment for DLBCL as part of other combination regimens.
Now that Epizyme has resolved the U.S. hold on tazemetostat trials, the company is working to resolve partial clinical holds placed in France and Germany to resume trial enrollment in those countries.
The U.S. Food and Drug Administration (FDA) has lifted the partial clinical hold on trials of tazemetostat, an EZH2 inhibitor being developed to treat solid tumors and lymphomas.
The FDA had placed the hold in April, and this halted U.S.-based enrollment of new patients in tazemetostat clinical trials.
Now, Epizyme, Inc., the company developing tazemetostat, is in the process of reopening enrollment in all company-sponsored trials in the U.S.
The FDA had placed the partial hold on tazemetostat trials after an adverse event was observed in a pediatric patient on a phase 1 study.
The patient, who had advanced poorly differentiated chordoma, developed secondary T-cell lymphoblastic lymphoma (T-LBL) while taking tazemetostat. The patient has since discontinued tazemetostat and responded to treatment for T-LBL.
“This remains the only case of T-LBL we’ve seen in more than 750 patients treated with tazemetostat,” said Robert Bazemore, president and chief executive officer of Epizyme.
Due to this adverse event and the partial clinical hold, Epizyme began to assess the risk of T-LBL and other secondary malignancies potentially associated with tazemetostat.
The company also assessed the overall risks and benefits of tazemetostat treatment, conducting a review of the published literature and an examination of efficacy and safety data across all of its tazemetostat trials.
Epizyme concluded that the benefits of tazemetostat outweigh the risks, and the risk of T-LBL appears confined to pediatric patients who received higher doses of the drug. The phase 1 pediatric study in which the patient developed T-LBL included higher doses of tazemetostat than those used in the phase 2 adult studies.
Epizyme convened a panel of external scientific and medical experts who reviewed and validated the company’s findings.
“The team at Epizyme has worked diligently in collaboration with external experts and FDA over the past several months, culminating in decisions . . . to lift the partial clinical hold and allow re-opening of enrollment in our clinical trials,” Bazemore said.
He noted that the company is not making any substantial changes to trial designs or the patient populations involved in tazemetostat trials.
However, Epizyme is modifying dosing in the pediatric studies, improving patient monitoring, and making changes to exclusion criteria to reduce the potential risk of T-LBL and other secondary malignancies.
Bazemore said the lifting of the partial clinical hold allows Epizyme to turn its full attention to key priorities, including plans to submit a new drug application for tazemetostat in epithelioid sarcoma.
The company also plans to begin preparing for a potential new drug application for tazemetostat in follicular lymphoma.
Tazemetostat is currently under investigation as monotherapy in phase 2 trials of follicular lymphoma and solid tumor malignancies. The drug is also being studied as part of combination therapy for non-small cell lung cancer and diffuse large B-cell lymphoma (DLBCL).
In August, Epizyme announced its decision to stop developing tazemetostat for use as monotherapy or in combination with prednisolone for patients with DLBCL. However, tazemetostat is still under investigation as a potential treatment for DLBCL as part of other combination regimens.
Now that Epizyme has resolved the U.S. hold on tazemetostat trials, the company is working to resolve partial clinical holds placed in France and Germany to resume trial enrollment in those countries.
Blinatumomab approved to treat ALL in Japan
The Japanese Ministry of Health, Labour and Welfare has approved blinatumomab (Blincyto®) for the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL).
Blinatumomab is the first and only bispecific T-cell engager immunotherapy construct approved globally.
The drug’s approval in Japan is based on data from the phase 3 TOWER study and the phase 1b/2 Horai study.
The TOWER trial (NCT02013167) enrolled 405 patients with Ph-negative, relapsed/refractory B-ALL, 376 of whom ultimately received treatment.
The patients received blinatumomab (n=267) or investigator’s choice of four protocol-defined standard of care (SOC) chemotherapy regimens (n=109):
- FLAG (fludarabine, high-dose cytarabine arabinoside, and granulocyte-colony stimulating factor), with or without an anthracycline (n=49, 45%)
- A high-dose cytarabine arabinoside-based regimen (n=19, 17%)
- A high-dose methotrexate-based regimen (n=22, 20%)
- A clofarabine-based regimen (n=19, 17%).
Blinatumomab demonstrated an improvement in median overall survival over SOC. The median overall survival was 7.7 months with blinatumomab and 4.0 months with SOC (hazard ratio for death=0.71; P=0.012).
Grade 3 or higher adverse events (AEs) of interest, according to the researchers, were:
- Infection (34% with blinatumomab and 52% with chemotherapy)
- Neutropenia (38% and 58%, respectively)
- Elevated liver enzymes (13% and 15%, respectively)
- Neurologic events (9% and 8%, respectively)
- Cytokine release syndrome (5% and 0%, respectively)
- Infusion reactions (3% and 1%, respectively)
- Lymphopenia (2% and 4%, respectively).
Fatal AEs occurred in 19% of patients in the blinatumomab arm and 17% of those in the SOC arm.
These results were published in The New England Journal of Medicine last year.
Horai
For this single-arm trial (NCT02412306), researchers evaluated blinatumomab in 35 Japanese adult and pediatric patients with relapsed or refractory B-ALL. An extension of this study is ongoing.
Efficacy data from Horai are not available.
According to Amgen, the major AEs occurring in adults on this trial were cytokine release syndrome (46.2%), pyrexia (46.2%), decrease in white blood cell count (38.5%), and decrease in platelet count (34.6%).
Major AEs in pediatric patients were elevated liver enzymes (66.7%), pyrexia (66.7%), cytokine release syndrome (55.6%), and abdominal pain (44.4%).
The Japanese Ministry of Health, Labour and Welfare has approved blinatumomab (Blincyto®) for the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL).
Blinatumomab is the first and only bispecific T-cell engager immunotherapy construct approved globally.
The drug’s approval in Japan is based on data from the phase 3 TOWER study and the phase 1b/2 Horai study.
The TOWER trial (NCT02013167) enrolled 405 patients with Ph-negative, relapsed/refractory B-ALL, 376 of whom ultimately received treatment.
The patients received blinatumomab (n=267) or investigator’s choice of four protocol-defined standard of care (SOC) chemotherapy regimens (n=109):
- FLAG (fludarabine, high-dose cytarabine arabinoside, and granulocyte-colony stimulating factor), with or without an anthracycline (n=49, 45%)
- A high-dose cytarabine arabinoside-based regimen (n=19, 17%)
- A high-dose methotrexate-based regimen (n=22, 20%)
- A clofarabine-based regimen (n=19, 17%).
Blinatumomab demonstrated an improvement in median overall survival over SOC. The median overall survival was 7.7 months with blinatumomab and 4.0 months with SOC (hazard ratio for death=0.71; P=0.012).
Grade 3 or higher adverse events (AEs) of interest, according to the researchers, were:
- Infection (34% with blinatumomab and 52% with chemotherapy)
- Neutropenia (38% and 58%, respectively)
- Elevated liver enzymes (13% and 15%, respectively)
- Neurologic events (9% and 8%, respectively)
- Cytokine release syndrome (5% and 0%, respectively)
- Infusion reactions (3% and 1%, respectively)
- Lymphopenia (2% and 4%, respectively).
Fatal AEs occurred in 19% of patients in the blinatumomab arm and 17% of those in the SOC arm.
These results were published in The New England Journal of Medicine last year.
Horai
For this single-arm trial (NCT02412306), researchers evaluated blinatumomab in 35 Japanese adult and pediatric patients with relapsed or refractory B-ALL. An extension of this study is ongoing.
Efficacy data from Horai are not available.
According to Amgen, the major AEs occurring in adults on this trial were cytokine release syndrome (46.2%), pyrexia (46.2%), decrease in white blood cell count (38.5%), and decrease in platelet count (34.6%).
Major AEs in pediatric patients were elevated liver enzymes (66.7%), pyrexia (66.7%), cytokine release syndrome (55.6%), and abdominal pain (44.4%).
The Japanese Ministry of Health, Labour and Welfare has approved blinatumomab (Blincyto®) for the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL).
Blinatumomab is the first and only bispecific T-cell engager immunotherapy construct approved globally.
The drug’s approval in Japan is based on data from the phase 3 TOWER study and the phase 1b/2 Horai study.
The TOWER trial (NCT02013167) enrolled 405 patients with Ph-negative, relapsed/refractory B-ALL, 376 of whom ultimately received treatment.
The patients received blinatumomab (n=267) or investigator’s choice of four protocol-defined standard of care (SOC) chemotherapy regimens (n=109):
- FLAG (fludarabine, high-dose cytarabine arabinoside, and granulocyte-colony stimulating factor), with or without an anthracycline (n=49, 45%)
- A high-dose cytarabine arabinoside-based regimen (n=19, 17%)
- A high-dose methotrexate-based regimen (n=22, 20%)
- A clofarabine-based regimen (n=19, 17%).
Blinatumomab demonstrated an improvement in median overall survival over SOC. The median overall survival was 7.7 months with blinatumomab and 4.0 months with SOC (hazard ratio for death=0.71; P=0.012).
Grade 3 or higher adverse events (AEs) of interest, according to the researchers, were:
- Infection (34% with blinatumomab and 52% with chemotherapy)
- Neutropenia (38% and 58%, respectively)
- Elevated liver enzymes (13% and 15%, respectively)
- Neurologic events (9% and 8%, respectively)
- Cytokine release syndrome (5% and 0%, respectively)
- Infusion reactions (3% and 1%, respectively)
- Lymphopenia (2% and 4%, respectively).
Fatal AEs occurred in 19% of patients in the blinatumomab arm and 17% of those in the SOC arm.
These results were published in The New England Journal of Medicine last year.
Horai
For this single-arm trial (NCT02412306), researchers evaluated blinatumomab in 35 Japanese adult and pediatric patients with relapsed or refractory B-ALL. An extension of this study is ongoing.
Efficacy data from Horai are not available.
According to Amgen, the major AEs occurring in adults on this trial were cytokine release syndrome (46.2%), pyrexia (46.2%), decrease in white blood cell count (38.5%), and decrease in platelet count (34.6%).
Major AEs in pediatric patients were elevated liver enzymes (66.7%), pyrexia (66.7%), cytokine release syndrome (55.6%), and abdominal pain (44.4%).
FDA approves duvelisib for CLL/SLL and FL
The U.S. Food and Drug Administration (FDA) has approved duvelisib (Copiktra™), a dual PI3K delta/gamma inhibitor, for two indications.
Duvelisib has full FDA approval to treat adults with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have received at least two prior therapies.
Duvelisib also has accelerated approval to treat adults with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.
Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit. Continued approval of duvelisib in FL may be contingent upon results of confirmatory trials verifying that the drug provides a clinical benefit.
Duvelisib will be available in the U.S. immediately, according to Verastem Inc., the company marketing the drug.
Verastem said it will help patients access duvelisib through the Verastem Cares™ program, which is designed to provide information and assistance to patients who are prescribed duvelisib.
The prescribing information for duvelisib includes a boxed warning detailing four fatal and/or serious toxicities associated with the drug—infections, diarrhea or colitis, cutaneous reactions, and pneumonitis.
Verastem said it is implementing an informational risk evaluation and mitigation strategy to provide appropriate dosing and safety information for duvelisib.
The recommended dose of duvelisib is 25 mg orally twice daily, taken continuously in 28-day treatment cycles.
The FDA assessed the new drug application for duvelisib under priority review. The FDA also granted duvelisib fast track designation in CLL and FL as well as orphan drug designation for CLL/SLL and FL.
The FDA’s approval of duvelisib is supported by data from the phase 3 DUO trial and the phase 2 DYNAMO trial. Updated results from both studies are available in the prescribing information for duvelisib.
DUO trial
DUO included 319 patients with CLL (n=312) or SLL (n=7) who had received at least one prior therapy. They were randomized to receive either duvelisib (25 mg orally twice daily) or ofatumumab (initial infusion of 300 mg followed by 7 weekly infusions and 4 monthly infusions of 2000 mg).
The following efficacy results were observed in patients who had received at least two prior therapies, which includes 95 patients in the duvelisib arm and 101 in the ofatumumab arm.
The overall response rate was 78% in the duvelisib arm and 39% in the ofatumumab arm. All responses in both arms were partial responses.
The median progression-free survival was 16.4 months with duvelisib and 9.1 months with ofatumumab (hazard ratio=0.40).
The safety results include all patients treated with duvelisib or ofatumumab.
Twelve percent of patients in the duvelisib arm had fatal adverse events (AEs) within 30 days of the last dose. The same was true of 4% of patients treated with ofatumumab.
Serious AEs occurred in 73% of patients treated with duvelisib. The most common were infection (38%) and diarrhea/colitis (23%).
Thirty-six percent of patients discontinued duvelisib. Most discontinuations were due to diarrhea/ colitis, infection, and rash. Twenty-nine percent of patients in the duvelisib arm required dose reductions, most often due to diarrhea/colitis and rash.
DYNAMO trial
DYNAMO enrolled patients with indolent non-Hodgkin lymphoma whose disease was refractory to both rituximab and chemotherapy or radioimmunotherapy.
There were 83 patients with FL. They had a median of 3 prior anticancer regimens (range, 1-10).
The patients received duvelisib at 25 mg orally twice daily until disease progression or unacceptable toxicity.
The overall response rate was 42%. One patient achieved a complete response, and 34 had a partial response.
Forty-three percent of responders maintained their response at 6 months, and 17% maintained their response at 12 months.
Serious AEs occurred in 58% of FL patients. The most common were diarrhea/colitis, pneumonia, renal insufficiency, rash, and sepsis.
AEs occurring in at least 20% of FL patients included diarrhea/colitis, nausea, fatigue, musculoskeletal pain, rash, neutropenia, cough, anemia, pyrexia, headache, mucositis, abdominal pain, vomiting, transaminase elevation, and thrombocytopenia.
Twenty-nine percent of FL patients discontinued duvelisib, and 23% had dose reductions. Most discontinuations were due to diarrhea/colitis and rash, and most dose reductions were due to transaminase elevation, diarrhea/colitis, lipase increase, and infection.
The U.S. Food and Drug Administration (FDA) has approved duvelisib (Copiktra™), a dual PI3K delta/gamma inhibitor, for two indications.
Duvelisib has full FDA approval to treat adults with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have received at least two prior therapies.
Duvelisib also has accelerated approval to treat adults with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.
Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit. Continued approval of duvelisib in FL may be contingent upon results of confirmatory trials verifying that the drug provides a clinical benefit.
Duvelisib will be available in the U.S. immediately, according to Verastem Inc., the company marketing the drug.
Verastem said it will help patients access duvelisib through the Verastem Cares™ program, which is designed to provide information and assistance to patients who are prescribed duvelisib.
The prescribing information for duvelisib includes a boxed warning detailing four fatal and/or serious toxicities associated with the drug—infections, diarrhea or colitis, cutaneous reactions, and pneumonitis.
Verastem said it is implementing an informational risk evaluation and mitigation strategy to provide appropriate dosing and safety information for duvelisib.
The recommended dose of duvelisib is 25 mg orally twice daily, taken continuously in 28-day treatment cycles.
The FDA assessed the new drug application for duvelisib under priority review. The FDA also granted duvelisib fast track designation in CLL and FL as well as orphan drug designation for CLL/SLL and FL.
The FDA’s approval of duvelisib is supported by data from the phase 3 DUO trial and the phase 2 DYNAMO trial. Updated results from both studies are available in the prescribing information for duvelisib.
DUO trial
DUO included 319 patients with CLL (n=312) or SLL (n=7) who had received at least one prior therapy. They were randomized to receive either duvelisib (25 mg orally twice daily) or ofatumumab (initial infusion of 300 mg followed by 7 weekly infusions and 4 monthly infusions of 2000 mg).
The following efficacy results were observed in patients who had received at least two prior therapies, which includes 95 patients in the duvelisib arm and 101 in the ofatumumab arm.
The overall response rate was 78% in the duvelisib arm and 39% in the ofatumumab arm. All responses in both arms were partial responses.
The median progression-free survival was 16.4 months with duvelisib and 9.1 months with ofatumumab (hazard ratio=0.40).
The safety results include all patients treated with duvelisib or ofatumumab.
Twelve percent of patients in the duvelisib arm had fatal adverse events (AEs) within 30 days of the last dose. The same was true of 4% of patients treated with ofatumumab.
Serious AEs occurred in 73% of patients treated with duvelisib. The most common were infection (38%) and diarrhea/colitis (23%).
Thirty-six percent of patients discontinued duvelisib. Most discontinuations were due to diarrhea/ colitis, infection, and rash. Twenty-nine percent of patients in the duvelisib arm required dose reductions, most often due to diarrhea/colitis and rash.
DYNAMO trial
DYNAMO enrolled patients with indolent non-Hodgkin lymphoma whose disease was refractory to both rituximab and chemotherapy or radioimmunotherapy.
There were 83 patients with FL. They had a median of 3 prior anticancer regimens (range, 1-10).
The patients received duvelisib at 25 mg orally twice daily until disease progression or unacceptable toxicity.
The overall response rate was 42%. One patient achieved a complete response, and 34 had a partial response.
Forty-three percent of responders maintained their response at 6 months, and 17% maintained their response at 12 months.
Serious AEs occurred in 58% of FL patients. The most common were diarrhea/colitis, pneumonia, renal insufficiency, rash, and sepsis.
AEs occurring in at least 20% of FL patients included diarrhea/colitis, nausea, fatigue, musculoskeletal pain, rash, neutropenia, cough, anemia, pyrexia, headache, mucositis, abdominal pain, vomiting, transaminase elevation, and thrombocytopenia.
Twenty-nine percent of FL patients discontinued duvelisib, and 23% had dose reductions. Most discontinuations were due to diarrhea/colitis and rash, and most dose reductions were due to transaminase elevation, diarrhea/colitis, lipase increase, and infection.
The U.S. Food and Drug Administration (FDA) has approved duvelisib (Copiktra™), a dual PI3K delta/gamma inhibitor, for two indications.
Duvelisib has full FDA approval to treat adults with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have received at least two prior therapies.
Duvelisib also has accelerated approval to treat adults with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.
Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit. Continued approval of duvelisib in FL may be contingent upon results of confirmatory trials verifying that the drug provides a clinical benefit.
Duvelisib will be available in the U.S. immediately, according to Verastem Inc., the company marketing the drug.
Verastem said it will help patients access duvelisib through the Verastem Cares™ program, which is designed to provide information and assistance to patients who are prescribed duvelisib.
The prescribing information for duvelisib includes a boxed warning detailing four fatal and/or serious toxicities associated with the drug—infections, diarrhea or colitis, cutaneous reactions, and pneumonitis.
Verastem said it is implementing an informational risk evaluation and mitigation strategy to provide appropriate dosing and safety information for duvelisib.
The recommended dose of duvelisib is 25 mg orally twice daily, taken continuously in 28-day treatment cycles.
The FDA assessed the new drug application for duvelisib under priority review. The FDA also granted duvelisib fast track designation in CLL and FL as well as orphan drug designation for CLL/SLL and FL.
The FDA’s approval of duvelisib is supported by data from the phase 3 DUO trial and the phase 2 DYNAMO trial. Updated results from both studies are available in the prescribing information for duvelisib.
DUO trial
DUO included 319 patients with CLL (n=312) or SLL (n=7) who had received at least one prior therapy. They were randomized to receive either duvelisib (25 mg orally twice daily) or ofatumumab (initial infusion of 300 mg followed by 7 weekly infusions and 4 monthly infusions of 2000 mg).
The following efficacy results were observed in patients who had received at least two prior therapies, which includes 95 patients in the duvelisib arm and 101 in the ofatumumab arm.
The overall response rate was 78% in the duvelisib arm and 39% in the ofatumumab arm. All responses in both arms were partial responses.
The median progression-free survival was 16.4 months with duvelisib and 9.1 months with ofatumumab (hazard ratio=0.40).
The safety results include all patients treated with duvelisib or ofatumumab.
Twelve percent of patients in the duvelisib arm had fatal adverse events (AEs) within 30 days of the last dose. The same was true of 4% of patients treated with ofatumumab.
Serious AEs occurred in 73% of patients treated with duvelisib. The most common were infection (38%) and diarrhea/colitis (23%).
Thirty-six percent of patients discontinued duvelisib. Most discontinuations were due to diarrhea/ colitis, infection, and rash. Twenty-nine percent of patients in the duvelisib arm required dose reductions, most often due to diarrhea/colitis and rash.
DYNAMO trial
DYNAMO enrolled patients with indolent non-Hodgkin lymphoma whose disease was refractory to both rituximab and chemotherapy or radioimmunotherapy.
There were 83 patients with FL. They had a median of 3 prior anticancer regimens (range, 1-10).
The patients received duvelisib at 25 mg orally twice daily until disease progression or unacceptable toxicity.
The overall response rate was 42%. One patient achieved a complete response, and 34 had a partial response.
Forty-three percent of responders maintained their response at 6 months, and 17% maintained their response at 12 months.
Serious AEs occurred in 58% of FL patients. The most common were diarrhea/colitis, pneumonia, renal insufficiency, rash, and sepsis.
AEs occurring in at least 20% of FL patients included diarrhea/colitis, nausea, fatigue, musculoskeletal pain, rash, neutropenia, cough, anemia, pyrexia, headache, mucositis, abdominal pain, vomiting, transaminase elevation, and thrombocytopenia.
Twenty-nine percent of FL patients discontinued duvelisib, and 23% had dose reductions. Most discontinuations were due to diarrhea/colitis and rash, and most dose reductions were due to transaminase elevation, diarrhea/colitis, lipase increase, and infection.
FLT3 inhibitor approved for rel/ref AML in Japan
The Japanese Ministry of Health, Labour and Welfare (MHLW) has approved the FLT3 inhibitor gilteritinib (Xospata®) to treat patients with FLT3-positive relapsed or refractory acute myeloid leukemia (AML).
Gilteritinib is available in 40 mg tablets. The usual recommended starting dose of gilteritinib for an adult is 120 mg once daily.
The dosage may be adjusted depending on the patient’s condition. However, the daily maximum dose should be 200 mg.
Gilteritinib has demonstrated inhibitory activity against FLT3 internal tandem duplication and FLT tyrosine kinase domain mutation. These two mutations are present in approximately one-third of AML patients.
The MHLW approval of gilteritinib is based on interim results from the phase 3 ADMIRAL study (NCT02421939).
ADIMRAL is designed to compare gilteritinib to salvage chemotherapy in adults who have AML with FLT3 mutations and have relapsed after or are refractory to frontline therapy.
Patients are randomized in a 2:1 ratio to receive gilteritinib (120 mg) or salvage chemotherapy, which may consist of low-dose cytarabine, azacitidine, MEC (mitoxantrone, etoposide, and cytarabine), or FLAG-IDA (fludarabine, cytarabine, and granulocyte colony-stimulating factor [G-CSF] with idarubicin).
Results from this trial have not yet been presented or published. However, a description of the trial was presented at the 2018 ASCO Annual Meeting (abstract TPS7075).
Results from a phase 1/2 study of gilteritinib in AML were published in The Lancet Oncology in 2017.
Orphan and SAKIGAKE designations
The MHLW previously granted SAKIGAKE designation and orphan drug designation to gilteritinib.
To receive orphan designation, a product (drug or medical device) must be intended for use in less than 50,000 patients in Japan. Furthermore, orphan products must be indicated for the treatment of serious diseases for which there are high medical needs.
Companies granted orphan designation can receive preferential tax treatment as well as subsidies through the National Institute of Biomedical Innovation (NIBIO) to reduce the financial burden of product development.
Companies with orphan designation can also receive guidance and consultation from the MHLW, the Pharmaceuticals and Medical Devices Agency (PMDA), and NIBIO on research and development activities.
Orphan designation also allows for priority review and an extension of the re-examination period—up to 10 years for drugs and up to 7 years for medical devices.
SAKIGAKE designation can shorten the review period for a product via prioritized consultation, substantial pre-application consultation, and prioritized review.
SAKIGAKE designation also helps promote development with the review partner system (to be conducted by the PMDA) and “substantial” post-marketing safety measures.
The Japanese Ministry of Health, Labour and Welfare (MHLW) has approved the FLT3 inhibitor gilteritinib (Xospata®) to treat patients with FLT3-positive relapsed or refractory acute myeloid leukemia (AML).
Gilteritinib is available in 40 mg tablets. The usual recommended starting dose of gilteritinib for an adult is 120 mg once daily.
The dosage may be adjusted depending on the patient’s condition. However, the daily maximum dose should be 200 mg.
Gilteritinib has demonstrated inhibitory activity against FLT3 internal tandem duplication and FLT tyrosine kinase domain mutation. These two mutations are present in approximately one-third of AML patients.
The MHLW approval of gilteritinib is based on interim results from the phase 3 ADMIRAL study (NCT02421939).
ADIMRAL is designed to compare gilteritinib to salvage chemotherapy in adults who have AML with FLT3 mutations and have relapsed after or are refractory to frontline therapy.
Patients are randomized in a 2:1 ratio to receive gilteritinib (120 mg) or salvage chemotherapy, which may consist of low-dose cytarabine, azacitidine, MEC (mitoxantrone, etoposide, and cytarabine), or FLAG-IDA (fludarabine, cytarabine, and granulocyte colony-stimulating factor [G-CSF] with idarubicin).
Results from this trial have not yet been presented or published. However, a description of the trial was presented at the 2018 ASCO Annual Meeting (abstract TPS7075).
Results from a phase 1/2 study of gilteritinib in AML were published in The Lancet Oncology in 2017.
Orphan and SAKIGAKE designations
The MHLW previously granted SAKIGAKE designation and orphan drug designation to gilteritinib.
To receive orphan designation, a product (drug or medical device) must be intended for use in less than 50,000 patients in Japan. Furthermore, orphan products must be indicated for the treatment of serious diseases for which there are high medical needs.
Companies granted orphan designation can receive preferential tax treatment as well as subsidies through the National Institute of Biomedical Innovation (NIBIO) to reduce the financial burden of product development.
Companies with orphan designation can also receive guidance and consultation from the MHLW, the Pharmaceuticals and Medical Devices Agency (PMDA), and NIBIO on research and development activities.
Orphan designation also allows for priority review and an extension of the re-examination period—up to 10 years for drugs and up to 7 years for medical devices.
SAKIGAKE designation can shorten the review period for a product via prioritized consultation, substantial pre-application consultation, and prioritized review.
SAKIGAKE designation also helps promote development with the review partner system (to be conducted by the PMDA) and “substantial” post-marketing safety measures.
The Japanese Ministry of Health, Labour and Welfare (MHLW) has approved the FLT3 inhibitor gilteritinib (Xospata®) to treat patients with FLT3-positive relapsed or refractory acute myeloid leukemia (AML).
Gilteritinib is available in 40 mg tablets. The usual recommended starting dose of gilteritinib for an adult is 120 mg once daily.
The dosage may be adjusted depending on the patient’s condition. However, the daily maximum dose should be 200 mg.
Gilteritinib has demonstrated inhibitory activity against FLT3 internal tandem duplication and FLT tyrosine kinase domain mutation. These two mutations are present in approximately one-third of AML patients.
The MHLW approval of gilteritinib is based on interim results from the phase 3 ADMIRAL study (NCT02421939).
ADIMRAL is designed to compare gilteritinib to salvage chemotherapy in adults who have AML with FLT3 mutations and have relapsed after or are refractory to frontline therapy.
Patients are randomized in a 2:1 ratio to receive gilteritinib (120 mg) or salvage chemotherapy, which may consist of low-dose cytarabine, azacitidine, MEC (mitoxantrone, etoposide, and cytarabine), or FLAG-IDA (fludarabine, cytarabine, and granulocyte colony-stimulating factor [G-CSF] with idarubicin).
Results from this trial have not yet been presented or published. However, a description of the trial was presented at the 2018 ASCO Annual Meeting (abstract TPS7075).
Results from a phase 1/2 study of gilteritinib in AML were published in The Lancet Oncology in 2017.
Orphan and SAKIGAKE designations
The MHLW previously granted SAKIGAKE designation and orphan drug designation to gilteritinib.
To receive orphan designation, a product (drug or medical device) must be intended for use in less than 50,000 patients in Japan. Furthermore, orphan products must be indicated for the treatment of serious diseases for which there are high medical needs.
Companies granted orphan designation can receive preferential tax treatment as well as subsidies through the National Institute of Biomedical Innovation (NIBIO) to reduce the financial burden of product development.
Companies with orphan designation can also receive guidance and consultation from the MHLW, the Pharmaceuticals and Medical Devices Agency (PMDA), and NIBIO on research and development activities.
Orphan designation also allows for priority review and an extension of the re-examination period—up to 10 years for drugs and up to 7 years for medical devices.
SAKIGAKE designation can shorten the review period for a product via prioritized consultation, substantial pre-application consultation, and prioritized review.
SAKIGAKE designation also helps promote development with the review partner system (to be conducted by the PMDA) and “substantial” post-marketing safety measures.
Drug approved as part of frontline therapy for HL
The Japanese Ministry of Health, Labour and Welfare has approved brentuximab vedotin (Adcetris) in combination with doxorubicin, vinblastine, and dacarbazine as a frontline treatment option for CD30-positive Hodgkin lymphoma (HL).
The approval was based on the phase 3 ECHELON-1 trial.
Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.
In this trial, researchers compared brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for 1334 patients with advanced HL.
The primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.
According to an independent review committee, A+AVD provided a significant improvement in modified PFS compared to ABVD. The hazard ratio was 0.77 (P=0.035), which corresponds to a 23% reduction in the risk of progression, death, or the need for additional anticancer therapy.
The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm.
There was no significant difference between the treatment arms when it came to response rates or overall survival.
The objective response rate was 86% in the A+AVD arm and 83% in the ABVD arm (P=0.12). The complete response rate was 73% and 70%, respectively (P=0.22).
The interim 2-year overall survival rate was 97% in the A+AVD arm and 95% in the ABVD arm (hazard ratio=0.72; P=0.19).
The overall incidence of adverse events (AEs) was 99% in the A+AVD arm and 98% in the ABVD arm. The incidence of grade 3 or higher AEs was 83% and 66%, respectively, and the incidence of serious AEs was 43% and 27%, respectively.
Neutropenia, febrile neutropenia, and peripheral neuropathy were more common with A+AVD, while pulmonary toxicity was more common with ABVD.
The Japanese Ministry of Health, Labour and Welfare has approved brentuximab vedotin (Adcetris) in combination with doxorubicin, vinblastine, and dacarbazine as a frontline treatment option for CD30-positive Hodgkin lymphoma (HL).
The approval was based on the phase 3 ECHELON-1 trial.
Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.
In this trial, researchers compared brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for 1334 patients with advanced HL.
The primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.
According to an independent review committee, A+AVD provided a significant improvement in modified PFS compared to ABVD. The hazard ratio was 0.77 (P=0.035), which corresponds to a 23% reduction in the risk of progression, death, or the need for additional anticancer therapy.
The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm.
There was no significant difference between the treatment arms when it came to response rates or overall survival.
The objective response rate was 86% in the A+AVD arm and 83% in the ABVD arm (P=0.12). The complete response rate was 73% and 70%, respectively (P=0.22).
The interim 2-year overall survival rate was 97% in the A+AVD arm and 95% in the ABVD arm (hazard ratio=0.72; P=0.19).
The overall incidence of adverse events (AEs) was 99% in the A+AVD arm and 98% in the ABVD arm. The incidence of grade 3 or higher AEs was 83% and 66%, respectively, and the incidence of serious AEs was 43% and 27%, respectively.
Neutropenia, febrile neutropenia, and peripheral neuropathy were more common with A+AVD, while pulmonary toxicity was more common with ABVD.
The Japanese Ministry of Health, Labour and Welfare has approved brentuximab vedotin (Adcetris) in combination with doxorubicin, vinblastine, and dacarbazine as a frontline treatment option for CD30-positive Hodgkin lymphoma (HL).
The approval was based on the phase 3 ECHELON-1 trial.
Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.
In this trial, researchers compared brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for 1334 patients with advanced HL.
The primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.
According to an independent review committee, A+AVD provided a significant improvement in modified PFS compared to ABVD. The hazard ratio was 0.77 (P=0.035), which corresponds to a 23% reduction in the risk of progression, death, or the need for additional anticancer therapy.
The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm.
There was no significant difference between the treatment arms when it came to response rates or overall survival.
The objective response rate was 86% in the A+AVD arm and 83% in the ABVD arm (P=0.12). The complete response rate was 73% and 70%, respectively (P=0.22).
The interim 2-year overall survival rate was 97% in the A+AVD arm and 95% in the ABVD arm (hazard ratio=0.72; P=0.19).
The overall incidence of adverse events (AEs) was 99% in the A+AVD arm and 98% in the ABVD arm. The incidence of grade 3 or higher AEs was 83% and 66%, respectively, and the incidence of serious AEs was 43% and 27%, respectively.
Neutropenia, febrile neutropenia, and peripheral neuropathy were more common with A+AVD, while pulmonary toxicity was more common with ABVD.
Product approved to treat hemophilia A in Japan
The Japanese Ministry of Health, Labour and Welfare has approved Jivi® (also known as damoctocog alfa pegol or antihemophilic factor [recombinant] PEGylated-aucl) for the treatment of hemophilia A.
Jivi (formerly BAY94-9027) is a DNA-derived, factor VIII concentrate approved for use in hemophilia A patients age 12 and older.
Jivi is approved for on-demand treatment and control of bleeding episodes, for perioperative management of bleeding, and as routine prophylaxis to reduce the frequency of bleeding episodes.
As prophylaxis, Jivi is typically given twice weekly, but it can also be given every 5 days or once a week, depending on patient needs.
The approval of Jivi in Japan is supported by data from the phase 2/3 PROTECT VIII trial. Some results from this trial were published in the Journal of Thrombosis and Haemostasis in 2016. Additional results are available in the U.S. prescribing information for Jivi.
PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.
In part A, researchers evaluated different dosing regimens for Jivi used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A.
In part B, researchers evaluated Jivi for perioperative management.
Efficacy
In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.
Patients received Jivi for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.
Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).
The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).
The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).
The median ABR for patients treated on demand was 24.1.
There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were considered “moderate,” and 3.3% were considered “poor.”
There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A. Jivi provided “good” or “excellent” hemostatic control during all surgeries.
Safety
Safety data are available for 148 patients age 12 and older.
Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).
A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.
One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.
The Japanese Ministry of Health, Labour and Welfare has approved Jivi® (also known as damoctocog alfa pegol or antihemophilic factor [recombinant] PEGylated-aucl) for the treatment of hemophilia A.
Jivi (formerly BAY94-9027) is a DNA-derived, factor VIII concentrate approved for use in hemophilia A patients age 12 and older.
Jivi is approved for on-demand treatment and control of bleeding episodes, for perioperative management of bleeding, and as routine prophylaxis to reduce the frequency of bleeding episodes.
As prophylaxis, Jivi is typically given twice weekly, but it can also be given every 5 days or once a week, depending on patient needs.
The approval of Jivi in Japan is supported by data from the phase 2/3 PROTECT VIII trial. Some results from this trial were published in the Journal of Thrombosis and Haemostasis in 2016. Additional results are available in the U.S. prescribing information for Jivi.
PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.
In part A, researchers evaluated different dosing regimens for Jivi used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A.
In part B, researchers evaluated Jivi for perioperative management.
Efficacy
In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.
Patients received Jivi for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.
Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).
The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).
The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).
The median ABR for patients treated on demand was 24.1.
There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were considered “moderate,” and 3.3% were considered “poor.”
There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A. Jivi provided “good” or “excellent” hemostatic control during all surgeries.
Safety
Safety data are available for 148 patients age 12 and older.
Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).
A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.
One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.
The Japanese Ministry of Health, Labour and Welfare has approved Jivi® (also known as damoctocog alfa pegol or antihemophilic factor [recombinant] PEGylated-aucl) for the treatment of hemophilia A.
Jivi (formerly BAY94-9027) is a DNA-derived, factor VIII concentrate approved for use in hemophilia A patients age 12 and older.
Jivi is approved for on-demand treatment and control of bleeding episodes, for perioperative management of bleeding, and as routine prophylaxis to reduce the frequency of bleeding episodes.
As prophylaxis, Jivi is typically given twice weekly, but it can also be given every 5 days or once a week, depending on patient needs.
The approval of Jivi in Japan is supported by data from the phase 2/3 PROTECT VIII trial. Some results from this trial were published in the Journal of Thrombosis and Haemostasis in 2016. Additional results are available in the U.S. prescribing information for Jivi.
PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.
In part A, researchers evaluated different dosing regimens for Jivi used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A.
In part B, researchers evaluated Jivi for perioperative management.
Efficacy
In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.
Patients received Jivi for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.
Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).
The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).
The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).
The median ABR for patients treated on demand was 24.1.
There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were considered “moderate,” and 3.3% were considered “poor.”
There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A. Jivi provided “good” or “excellent” hemostatic control during all surgeries.
Safety
Safety data are available for 148 patients age 12 and older.
Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).
A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.
One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.