User login
FDA: Clozapine REMS modified
The Food and Drug Administration has modified the Risk Evaluation and Mitigation Strategy (REMS) Program for clozapine, a second-generation antipsychotic used for patients who do not respond adequately to standard antipsychotic treatment. Use of clozapine comes with the risk of neutropenia, which can make patients vulnerable to serious infections, so routine monitoring of absolute neutrophil counts is a must.
The new requirements, including one that requires both prescribers and pharmacies to be certified in the clozapine REMS program, take effect Feb. 28.
More information about clozapine and this change can be found on the FDA web page for the drug.
The Food and Drug Administration has modified the Risk Evaluation and Mitigation Strategy (REMS) Program for clozapine, a second-generation antipsychotic used for patients who do not respond adequately to standard antipsychotic treatment. Use of clozapine comes with the risk of neutropenia, which can make patients vulnerable to serious infections, so routine monitoring of absolute neutrophil counts is a must.
The new requirements, including one that requires both prescribers and pharmacies to be certified in the clozapine REMS program, take effect Feb. 28.
More information about clozapine and this change can be found on the FDA web page for the drug.
The Food and Drug Administration has modified the Risk Evaluation and Mitigation Strategy (REMS) Program for clozapine, a second-generation antipsychotic used for patients who do not respond adequately to standard antipsychotic treatment. Use of clozapine comes with the risk of neutropenia, which can make patients vulnerable to serious infections, so routine monitoring of absolute neutrophil counts is a must.
The new requirements, including one that requires both prescribers and pharmacies to be certified in the clozapine REMS program, take effect Feb. 28.
More information about clozapine and this change can be found on the FDA web page for the drug.
FDA committee votes yes on romosozumab for osteoporosis
In an 18-1 vote, the FDA’s Bone, Reproductive, and Urologic Drugs Advisory Committee agreed that the risk-benefit profile of romosozumab, to be marketed by Amgen as Evenity, was favorable enough to support approval. Relative risk reductions of up to 75%, compared with placebo, and 36%, compared with alendronate, were seen in pivotal clinical trials.
A signal for increased major adverse cardiovascular events (MACE) among those receiving romosozumab had been seen in just one of the clinical trials, with a hazard ratio for MACE of 1.87 for those taking romosozumab, compared with those taking alendronate (95% confidence interval, 1.11-3.14).
Committee members were enthusiastic about the efficacy of the monoclonal antibody, which binds to sclerostin and prevents its inhibiting effect, allowing robust new bone formation. “I want to emphasize the remarkable skeletal efficacy of this drug; truly, it’s better than anything we’ve seen before,” said committee member Sundeep Khosla, MD, professor of medicine and physiology at the Mayo Clinic, Rochester, Minn.
In its application, the sponsor relied on two clinical trials. In the first, 7,180 women with osteoporosis aged 55-90 years were randomized 1:1 to receive romosozumab or placebo for 12 months in a double-blind trial. After this time, participants in each arm received follow-on treatment with denosumab (Prolia) for another 12 months. This study, dubbed Trial 337, followed morphometric vertebral fractures at 12 and 24 months. Morphometric fractures included both symptomatic and asymptomatic fractures.
Those treated with romosozumab had relative risk reductions of new vertebral fractures of 73% and 75%, compared with those given placebo at 12 and 24 months. Absolute risk reductions for vertebral fractures were 1.30% and 1.89% at 1 and 2 years (P less than .001 for both).
The second study, Trial 142, was a double-blind, active-controlled study that included 4,093 women aged 55-90 years with osteoporosis and a history of prior fragility fracture. Participants were randomized 1:1 to receive either romosozumab or alendronate for 12 months, with an additional variable period of alendronate follow-on of at least 12 months for both arms.
For Trial 142, one primary endpoint was morphometric vertebral fractures at month 24. An additional endpoint, clinical fracture, was a composite of symptomatic vertebral fractures and nonvertebral fractures. This second endpoint was assessed at the time of primary analysis, an event-driven cut point that occurred when at least 330 participants experienced a clinical fracture and all participants had completed the 24-month visit.
Hip fractures were less common among those given romosozumab, and bone mineral density increased significantly as well.
Vertebral fractures were reduced by 36% in the romosozumab group relative to the alendronate group, and clinical fractures by 27% (P less than .001 for both).
Overall, the number of adverse events for the more than 7,500 patients in the safety population was similar between those receiving romosozumab and either placebo or alendronate, said Scott Wasserman, MD, vice president of global development for Amgen.
However, in Trial 142, which included patients who were slightly older and on more cardiovascular medications at baseline than in Trial 337, MACE – defined as cardiovascular death, MI, and stroke – occurred more frequently among those taking romosozumab, driven primarily by increased cardiac and cerebral ischemic events occurring within the first 12 months of beginning the study drug. At 12 months, the romosozumab arm saw 41 instances of MACE, compared with 22 in the alendronate arm to produce the HR of 1.87 (2.0% vs. 1.1%).
With regard to the imbalance in MACE seen in Trial 142, both the FDA and presenters for the sponsor entertained the notion that alendronate may have been somewhat protective for cardiovascular events. Although there is some biologic plausibility for a cardioprotective event for bisphosphonates, alendronate is highly specific for bone activity and the preponderance of previous studies have not shown such cardioprotection, the FDA, sponsors, and committee members all agreed.
Marc Sabatine, MD, the Lewis Dexter, MD Distinguished Chair in Cardiovascular Medicine at Harvard Medical School, Boston, was available to answer questions on behalf of the study’s sponsor. He noted at several points during the meeting just how few total cardiovascular events were seen overall in the romosozumab trial. The overall small numbers, he said, made it very difficult to distinguish whether the smaller number of MACE seen in the alendronate arm of Trial 142 were a true safety signal or just “a play of chance.”
Almost all the committee’s questioning and discussion centered on this potential increased cardiovascular risk. Amgen, in discussion with the FDA, had agreed to a black box warning designed to wave off prescribing romosozumab to those at increased risk for cardiovascular disease, focusing on those with a history of MI or stroke.
Additionally, the sponsor proposed a postmarketing real-world observational study to track incidence of MACE in those receiving romosozumab, comparing them with those receiving standard of care for osteoporosis.
Several committee members pointed out a problem with the proposed safety mitigation scheme: By conducting a postmarketing observational study for a drug that has a black-box warning to exclude those at high risk for MACE, the chance of detecting an actual cardiovascular safety problem plummets. “This is the textbook example of when observational studies struggle or are virtually guaranteed to fail,” noted Tobias Gerhard, PhD, a pharmacoepidemiologist at Rutgers University, New Brunswick, N.J.
On the other hand, noted several committee members, pausing to conduct a premarketing randomized, controlled trial would keep a beneficial drug away from a population in need. A postmarketing randomized, controlled trial, even a simple trial, still presents challenges, some of the committee acknowledged. Dr. Khosla voiced the opinion that “A randomized, controlled trial is virtually impossible.”
The committee, which was charged with discussing, but not voting on, what additional data should be obtained – and when – to sort out the cardiovascular safety question, was approximately evenly divided in the matter of whether an observational or registry-based trial, or a controlled trial, would be the best path forward.
Committee member Robert A. Adler, MD, put a realistic frame around the debate. “As an endocrinologist, I deal with nuances every day. I really think the kind of clinician who is going to be using this drug is used to dealing with benefits and risks and trying to tailor treatment to a given patient,” said Dr. Adler, professor of internal medicine and epidemiology at Virginia Commonwealth University, Richmond.
In its proposed indication, Amgen defined the population of menopausal women at high risk of fracture as those with a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. Romosozumab would be given as a once-monthly subcutaneous injection of 210 mg for a period of 12 months, to be followed by antiresorptive therapy.
Most of the participants in the clinical trials resided outside the United States, primarily because of the difficulty of recruiting clinical trial participants in the United States, Amgen officials said during their presentation. However, neither the time to the first positively adjudicated MACE nor bone mineral density responses at month 12 differed significantly across the various geographic regions where clinical trial sites were located, said Rachel Wagman, MD, the executive medical director of global clinical development for Amgen. Still, several committee members called for postmarketing data to focus on U.S. patients.
Romosozumab was approved for marketing in Japan on Jan. 8, 2019; approval is also being sought in Europe .
The FDA usually follows the recommendations of its advisory panels.
In an 18-1 vote, the FDA’s Bone, Reproductive, and Urologic Drugs Advisory Committee agreed that the risk-benefit profile of romosozumab, to be marketed by Amgen as Evenity, was favorable enough to support approval. Relative risk reductions of up to 75%, compared with placebo, and 36%, compared with alendronate, were seen in pivotal clinical trials.
A signal for increased major adverse cardiovascular events (MACE) among those receiving romosozumab had been seen in just one of the clinical trials, with a hazard ratio for MACE of 1.87 for those taking romosozumab, compared with those taking alendronate (95% confidence interval, 1.11-3.14).
Committee members were enthusiastic about the efficacy of the monoclonal antibody, which binds to sclerostin and prevents its inhibiting effect, allowing robust new bone formation. “I want to emphasize the remarkable skeletal efficacy of this drug; truly, it’s better than anything we’ve seen before,” said committee member Sundeep Khosla, MD, professor of medicine and physiology at the Mayo Clinic, Rochester, Minn.
In its application, the sponsor relied on two clinical trials. In the first, 7,180 women with osteoporosis aged 55-90 years were randomized 1:1 to receive romosozumab or placebo for 12 months in a double-blind trial. After this time, participants in each arm received follow-on treatment with denosumab (Prolia) for another 12 months. This study, dubbed Trial 337, followed morphometric vertebral fractures at 12 and 24 months. Morphometric fractures included both symptomatic and asymptomatic fractures.
Those treated with romosozumab had relative risk reductions of new vertebral fractures of 73% and 75%, compared with those given placebo at 12 and 24 months. Absolute risk reductions for vertebral fractures were 1.30% and 1.89% at 1 and 2 years (P less than .001 for both).
The second study, Trial 142, was a double-blind, active-controlled study that included 4,093 women aged 55-90 years with osteoporosis and a history of prior fragility fracture. Participants were randomized 1:1 to receive either romosozumab or alendronate for 12 months, with an additional variable period of alendronate follow-on of at least 12 months for both arms.
For Trial 142, one primary endpoint was morphometric vertebral fractures at month 24. An additional endpoint, clinical fracture, was a composite of symptomatic vertebral fractures and nonvertebral fractures. This second endpoint was assessed at the time of primary analysis, an event-driven cut point that occurred when at least 330 participants experienced a clinical fracture and all participants had completed the 24-month visit.
Hip fractures were less common among those given romosozumab, and bone mineral density increased significantly as well.
Vertebral fractures were reduced by 36% in the romosozumab group relative to the alendronate group, and clinical fractures by 27% (P less than .001 for both).
Overall, the number of adverse events for the more than 7,500 patients in the safety population was similar between those receiving romosozumab and either placebo or alendronate, said Scott Wasserman, MD, vice president of global development for Amgen.
However, in Trial 142, which included patients who were slightly older and on more cardiovascular medications at baseline than in Trial 337, MACE – defined as cardiovascular death, MI, and stroke – occurred more frequently among those taking romosozumab, driven primarily by increased cardiac and cerebral ischemic events occurring within the first 12 months of beginning the study drug. At 12 months, the romosozumab arm saw 41 instances of MACE, compared with 22 in the alendronate arm to produce the HR of 1.87 (2.0% vs. 1.1%).
With regard to the imbalance in MACE seen in Trial 142, both the FDA and presenters for the sponsor entertained the notion that alendronate may have been somewhat protective for cardiovascular events. Although there is some biologic plausibility for a cardioprotective event for bisphosphonates, alendronate is highly specific for bone activity and the preponderance of previous studies have not shown such cardioprotection, the FDA, sponsors, and committee members all agreed.
Marc Sabatine, MD, the Lewis Dexter, MD Distinguished Chair in Cardiovascular Medicine at Harvard Medical School, Boston, was available to answer questions on behalf of the study’s sponsor. He noted at several points during the meeting just how few total cardiovascular events were seen overall in the romosozumab trial. The overall small numbers, he said, made it very difficult to distinguish whether the smaller number of MACE seen in the alendronate arm of Trial 142 were a true safety signal or just “a play of chance.”
Almost all the committee’s questioning and discussion centered on this potential increased cardiovascular risk. Amgen, in discussion with the FDA, had agreed to a black box warning designed to wave off prescribing romosozumab to those at increased risk for cardiovascular disease, focusing on those with a history of MI or stroke.
Additionally, the sponsor proposed a postmarketing real-world observational study to track incidence of MACE in those receiving romosozumab, comparing them with those receiving standard of care for osteoporosis.
Several committee members pointed out a problem with the proposed safety mitigation scheme: By conducting a postmarketing observational study for a drug that has a black-box warning to exclude those at high risk for MACE, the chance of detecting an actual cardiovascular safety problem plummets. “This is the textbook example of when observational studies struggle or are virtually guaranteed to fail,” noted Tobias Gerhard, PhD, a pharmacoepidemiologist at Rutgers University, New Brunswick, N.J.
On the other hand, noted several committee members, pausing to conduct a premarketing randomized, controlled trial would keep a beneficial drug away from a population in need. A postmarketing randomized, controlled trial, even a simple trial, still presents challenges, some of the committee acknowledged. Dr. Khosla voiced the opinion that “A randomized, controlled trial is virtually impossible.”
The committee, which was charged with discussing, but not voting on, what additional data should be obtained – and when – to sort out the cardiovascular safety question, was approximately evenly divided in the matter of whether an observational or registry-based trial, or a controlled trial, would be the best path forward.
Committee member Robert A. Adler, MD, put a realistic frame around the debate. “As an endocrinologist, I deal with nuances every day. I really think the kind of clinician who is going to be using this drug is used to dealing with benefits and risks and trying to tailor treatment to a given patient,” said Dr. Adler, professor of internal medicine and epidemiology at Virginia Commonwealth University, Richmond.
In its proposed indication, Amgen defined the population of menopausal women at high risk of fracture as those with a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. Romosozumab would be given as a once-monthly subcutaneous injection of 210 mg for a period of 12 months, to be followed by antiresorptive therapy.
Most of the participants in the clinical trials resided outside the United States, primarily because of the difficulty of recruiting clinical trial participants in the United States, Amgen officials said during their presentation. However, neither the time to the first positively adjudicated MACE nor bone mineral density responses at month 12 differed significantly across the various geographic regions where clinical trial sites were located, said Rachel Wagman, MD, the executive medical director of global clinical development for Amgen. Still, several committee members called for postmarketing data to focus on U.S. patients.
Romosozumab was approved for marketing in Japan on Jan. 8, 2019; approval is also being sought in Europe .
The FDA usually follows the recommendations of its advisory panels.
In an 18-1 vote, the FDA’s Bone, Reproductive, and Urologic Drugs Advisory Committee agreed that the risk-benefit profile of romosozumab, to be marketed by Amgen as Evenity, was favorable enough to support approval. Relative risk reductions of up to 75%, compared with placebo, and 36%, compared with alendronate, were seen in pivotal clinical trials.
A signal for increased major adverse cardiovascular events (MACE) among those receiving romosozumab had been seen in just one of the clinical trials, with a hazard ratio for MACE of 1.87 for those taking romosozumab, compared with those taking alendronate (95% confidence interval, 1.11-3.14).
Committee members were enthusiastic about the efficacy of the monoclonal antibody, which binds to sclerostin and prevents its inhibiting effect, allowing robust new bone formation. “I want to emphasize the remarkable skeletal efficacy of this drug; truly, it’s better than anything we’ve seen before,” said committee member Sundeep Khosla, MD, professor of medicine and physiology at the Mayo Clinic, Rochester, Minn.
In its application, the sponsor relied on two clinical trials. In the first, 7,180 women with osteoporosis aged 55-90 years were randomized 1:1 to receive romosozumab or placebo for 12 months in a double-blind trial. After this time, participants in each arm received follow-on treatment with denosumab (Prolia) for another 12 months. This study, dubbed Trial 337, followed morphometric vertebral fractures at 12 and 24 months. Morphometric fractures included both symptomatic and asymptomatic fractures.
Those treated with romosozumab had relative risk reductions of new vertebral fractures of 73% and 75%, compared with those given placebo at 12 and 24 months. Absolute risk reductions for vertebral fractures were 1.30% and 1.89% at 1 and 2 years (P less than .001 for both).
The second study, Trial 142, was a double-blind, active-controlled study that included 4,093 women aged 55-90 years with osteoporosis and a history of prior fragility fracture. Participants were randomized 1:1 to receive either romosozumab or alendronate for 12 months, with an additional variable period of alendronate follow-on of at least 12 months for both arms.
For Trial 142, one primary endpoint was morphometric vertebral fractures at month 24. An additional endpoint, clinical fracture, was a composite of symptomatic vertebral fractures and nonvertebral fractures. This second endpoint was assessed at the time of primary analysis, an event-driven cut point that occurred when at least 330 participants experienced a clinical fracture and all participants had completed the 24-month visit.
Hip fractures were less common among those given romosozumab, and bone mineral density increased significantly as well.
Vertebral fractures were reduced by 36% in the romosozumab group relative to the alendronate group, and clinical fractures by 27% (P less than .001 for both).
Overall, the number of adverse events for the more than 7,500 patients in the safety population was similar between those receiving romosozumab and either placebo or alendronate, said Scott Wasserman, MD, vice president of global development for Amgen.
However, in Trial 142, which included patients who were slightly older and on more cardiovascular medications at baseline than in Trial 337, MACE – defined as cardiovascular death, MI, and stroke – occurred more frequently among those taking romosozumab, driven primarily by increased cardiac and cerebral ischemic events occurring within the first 12 months of beginning the study drug. At 12 months, the romosozumab arm saw 41 instances of MACE, compared with 22 in the alendronate arm to produce the HR of 1.87 (2.0% vs. 1.1%).
With regard to the imbalance in MACE seen in Trial 142, both the FDA and presenters for the sponsor entertained the notion that alendronate may have been somewhat protective for cardiovascular events. Although there is some biologic plausibility for a cardioprotective event for bisphosphonates, alendronate is highly specific for bone activity and the preponderance of previous studies have not shown such cardioprotection, the FDA, sponsors, and committee members all agreed.
Marc Sabatine, MD, the Lewis Dexter, MD Distinguished Chair in Cardiovascular Medicine at Harvard Medical School, Boston, was available to answer questions on behalf of the study’s sponsor. He noted at several points during the meeting just how few total cardiovascular events were seen overall in the romosozumab trial. The overall small numbers, he said, made it very difficult to distinguish whether the smaller number of MACE seen in the alendronate arm of Trial 142 were a true safety signal or just “a play of chance.”
Almost all the committee’s questioning and discussion centered on this potential increased cardiovascular risk. Amgen, in discussion with the FDA, had agreed to a black box warning designed to wave off prescribing romosozumab to those at increased risk for cardiovascular disease, focusing on those with a history of MI or stroke.
Additionally, the sponsor proposed a postmarketing real-world observational study to track incidence of MACE in those receiving romosozumab, comparing them with those receiving standard of care for osteoporosis.
Several committee members pointed out a problem with the proposed safety mitigation scheme: By conducting a postmarketing observational study for a drug that has a black-box warning to exclude those at high risk for MACE, the chance of detecting an actual cardiovascular safety problem plummets. “This is the textbook example of when observational studies struggle or are virtually guaranteed to fail,” noted Tobias Gerhard, PhD, a pharmacoepidemiologist at Rutgers University, New Brunswick, N.J.
On the other hand, noted several committee members, pausing to conduct a premarketing randomized, controlled trial would keep a beneficial drug away from a population in need. A postmarketing randomized, controlled trial, even a simple trial, still presents challenges, some of the committee acknowledged. Dr. Khosla voiced the opinion that “A randomized, controlled trial is virtually impossible.”
The committee, which was charged with discussing, but not voting on, what additional data should be obtained – and when – to sort out the cardiovascular safety question, was approximately evenly divided in the matter of whether an observational or registry-based trial, or a controlled trial, would be the best path forward.
Committee member Robert A. Adler, MD, put a realistic frame around the debate. “As an endocrinologist, I deal with nuances every day. I really think the kind of clinician who is going to be using this drug is used to dealing with benefits and risks and trying to tailor treatment to a given patient,” said Dr. Adler, professor of internal medicine and epidemiology at Virginia Commonwealth University, Richmond.
In its proposed indication, Amgen defined the population of menopausal women at high risk of fracture as those with a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. Romosozumab would be given as a once-monthly subcutaneous injection of 210 mg for a period of 12 months, to be followed by antiresorptive therapy.
Most of the participants in the clinical trials resided outside the United States, primarily because of the difficulty of recruiting clinical trial participants in the United States, Amgen officials said during their presentation. However, neither the time to the first positively adjudicated MACE nor bone mineral density responses at month 12 differed significantly across the various geographic regions where clinical trial sites were located, said Rachel Wagman, MD, the executive medical director of global clinical development for Amgen. Still, several committee members called for postmarketing data to focus on U.S. patients.
Romosozumab was approved for marketing in Japan on Jan. 8, 2019; approval is also being sought in Europe .
The FDA usually follows the recommendations of its advisory panels.
FDA approves generic version of vigabatrin
The drug is approved for the adjunctive treatment of focal seizures in patients aged 10 years and older who have not had an adequate response to other therapies.
The approval was granted to Teva Pharmaceuticals.
An FDA announcement noted that the agency has prioritized the approval of generic versions of drugs to improve access to treatments and to lower drug costs. Vigabatrin had been included on an FDA list of off-patent, off-exclusivity branded drugs without approved generics. The approval of generic vigabatrin “demonstrates that there is an open pathway to approving products like this one,” said FDA Commissioner Scott Gottlieb, MD.
The label for vigabatrin tablets includes a boxed warning for permanent vision loss. The generic vigabatrin tablets are part of a single shared-system Risk Evaluation and Mitigation Strategy (REMS) program with other drug products containing vigabatrin.
The most common side effects associated with vigabatrin tablets include dizziness, fatigue, sleepiness, involuntary eye movement, tremor, blurred vision, memory impairment, weight gain, joint pain, upper respiratory tract infection, aggression, double vision, abnormal coordination, and a confused state. Serious side effects associated with vigabatrin tablets include permanent vision loss and risk of suicidal thoughts or actions.
The drug is approved for the adjunctive treatment of focal seizures in patients aged 10 years and older who have not had an adequate response to other therapies.
The approval was granted to Teva Pharmaceuticals.
An FDA announcement noted that the agency has prioritized the approval of generic versions of drugs to improve access to treatments and to lower drug costs. Vigabatrin had been included on an FDA list of off-patent, off-exclusivity branded drugs without approved generics. The approval of generic vigabatrin “demonstrates that there is an open pathway to approving products like this one,” said FDA Commissioner Scott Gottlieb, MD.
The label for vigabatrin tablets includes a boxed warning for permanent vision loss. The generic vigabatrin tablets are part of a single shared-system Risk Evaluation and Mitigation Strategy (REMS) program with other drug products containing vigabatrin.
The most common side effects associated with vigabatrin tablets include dizziness, fatigue, sleepiness, involuntary eye movement, tremor, blurred vision, memory impairment, weight gain, joint pain, upper respiratory tract infection, aggression, double vision, abnormal coordination, and a confused state. Serious side effects associated with vigabatrin tablets include permanent vision loss and risk of suicidal thoughts or actions.
The drug is approved for the adjunctive treatment of focal seizures in patients aged 10 years and older who have not had an adequate response to other therapies.
The approval was granted to Teva Pharmaceuticals.
An FDA announcement noted that the agency has prioritized the approval of generic versions of drugs to improve access to treatments and to lower drug costs. Vigabatrin had been included on an FDA list of off-patent, off-exclusivity branded drugs without approved generics. The approval of generic vigabatrin “demonstrates that there is an open pathway to approving products like this one,” said FDA Commissioner Scott Gottlieb, MD.
The label for vigabatrin tablets includes a boxed warning for permanent vision loss. The generic vigabatrin tablets are part of a single shared-system Risk Evaluation and Mitigation Strategy (REMS) program with other drug products containing vigabatrin.
The most common side effects associated with vigabatrin tablets include dizziness, fatigue, sleepiness, involuntary eye movement, tremor, blurred vision, memory impairment, weight gain, joint pain, upper respiratory tract infection, aggression, double vision, abnormal coordination, and a confused state. Serious side effects associated with vigabatrin tablets include permanent vision loss and risk of suicidal thoughts or actions.
FDA approves Adacel for repeat Tdap vaccinations
The Food and Drug Administration has approved the expanded use of Adacel (Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis (Tdap) Vaccine Adsorbed) to include repeat vaccinations 8 years or more after the first vaccination in people aged 10-64 years.
The expanded indication was based on results of a randomized, controlled trial, published in the Journal of the Pediatric Infectious Diseases Society, in which more than 1,300 adults aged 18-64 years received either Adacel or a Td (tetanus-diphtheria) vaccine 8-12 years after receiving a previous dose of Adacel.
Over the course of the study, no significant difference in adverse event incidence was observed between groups. Injection-site reaction was the most common adverse event during the study, occurring in 87.7% of those who received Adacel and 88.0% of those who received the Td vaccine. Other common adverse events associated with Adacel include headache, body ache or muscle weakness, tiredness, muscle aches, and general discomfort.
“While strong vaccination programs are in place for young adolescents, a single Tdap immunization does not offer lifetime protection against pertussis due to waning immunity. The licensure of Adacel as the first Tdap vaccine in the U.S. for repeat vaccination is an important step for eligible patients and offers flexibility for health care providers to help manage their immunization schedules,” said David P. Greenberg, MD, regional medical head North America at Sanofi Pasteur, in the press release.
Find the full press release on the Sanofi website.
The Food and Drug Administration has approved the expanded use of Adacel (Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis (Tdap) Vaccine Adsorbed) to include repeat vaccinations 8 years or more after the first vaccination in people aged 10-64 years.
The expanded indication was based on results of a randomized, controlled trial, published in the Journal of the Pediatric Infectious Diseases Society, in which more than 1,300 adults aged 18-64 years received either Adacel or a Td (tetanus-diphtheria) vaccine 8-12 years after receiving a previous dose of Adacel.
Over the course of the study, no significant difference in adverse event incidence was observed between groups. Injection-site reaction was the most common adverse event during the study, occurring in 87.7% of those who received Adacel and 88.0% of those who received the Td vaccine. Other common adverse events associated with Adacel include headache, body ache or muscle weakness, tiredness, muscle aches, and general discomfort.
“While strong vaccination programs are in place for young adolescents, a single Tdap immunization does not offer lifetime protection against pertussis due to waning immunity. The licensure of Adacel as the first Tdap vaccine in the U.S. for repeat vaccination is an important step for eligible patients and offers flexibility for health care providers to help manage their immunization schedules,” said David P. Greenberg, MD, regional medical head North America at Sanofi Pasteur, in the press release.
Find the full press release on the Sanofi website.
The Food and Drug Administration has approved the expanded use of Adacel (Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis (Tdap) Vaccine Adsorbed) to include repeat vaccinations 8 years or more after the first vaccination in people aged 10-64 years.
The expanded indication was based on results of a randomized, controlled trial, published in the Journal of the Pediatric Infectious Diseases Society, in which more than 1,300 adults aged 18-64 years received either Adacel or a Td (tetanus-diphtheria) vaccine 8-12 years after receiving a previous dose of Adacel.
Over the course of the study, no significant difference in adverse event incidence was observed between groups. Injection-site reaction was the most common adverse event during the study, occurring in 87.7% of those who received Adacel and 88.0% of those who received the Td vaccine. Other common adverse events associated with Adacel include headache, body ache or muscle weakness, tiredness, muscle aches, and general discomfort.
“While strong vaccination programs are in place for young adolescents, a single Tdap immunization does not offer lifetime protection against pertussis due to waning immunity. The licensure of Adacel as the first Tdap vaccine in the U.S. for repeat vaccination is an important step for eligible patients and offers flexibility for health care providers to help manage their immunization schedules,” said David P. Greenberg, MD, regional medical head North America at Sanofi Pasteur, in the press release.
Find the full press release on the Sanofi website.
FDA approves cabozantinib for previously treated HCC
The Food and Drug Administration has approved cabozantinib tablets (Cabometyx) for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.
Approval was based on an improvement in overall survival over placebo seen in the phase 3 CELESTIAL trial for patients with advanced HCC who received prior sorafenib.
Median overall survival was 10.2 months with cabozantinib versus 8.0 months with placebo (hazard ratio, 0.76; 95% confidence interval, 0.63-0.92; P = .0049). Median progression-free survival was 5.2 months with cabozantinib and 1.9 months with placebo (HR, 0.44; 95% CI, 0.36-0.52; P less than .0001). Objective response rates were 4% with cabozantinib and 0.4% with placebo (P = .0086), Exelixis, makers of the drug, said in a press release.
The most common grade 3 or 4 adverse events in the patients who received cabozantinib, compared with those who received placebo, were palmar-plantar erythrodysesthesia (17% vs. 0%), hypertension (16% vs. 2%), increased aspartate aminotransferase (12% vs. 7%), fatigue (10% vs. 4%), and diarrhea (10% vs. 2%). Treatment-related grade 5 adverse events occurred in six patients in the cabozantinib group (hepatic failure, esophagobronchial fistula, portal vein thrombosis, upper gastrointestinal hemorrhage, pulmonary embolism, and hepatorenal syndrome) and in one patient in the placebo group (hepatic failure).
Cabozantinib is also approved to treat renal cell carcinoma and medullary thyroid cancer.
Checkpoint inhibitor pembrolizumab was granted accelerated approval for the same HCC indication – to treat patients who have been previously treated with sorafenib – in late 2018.
Exelixis and its partner Ipsen have launched a phase 3 trial of cabozantinib in combination with the checkpoint inhibitor atezolizumab versus sorafenib in previously untreated advanced HCC. The trial will also explore single-agent activity of cabozantinib in the first-line setting, the company said in the press release.
The Food and Drug Administration has approved cabozantinib tablets (Cabometyx) for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.
Approval was based on an improvement in overall survival over placebo seen in the phase 3 CELESTIAL trial for patients with advanced HCC who received prior sorafenib.
Median overall survival was 10.2 months with cabozantinib versus 8.0 months with placebo (hazard ratio, 0.76; 95% confidence interval, 0.63-0.92; P = .0049). Median progression-free survival was 5.2 months with cabozantinib and 1.9 months with placebo (HR, 0.44; 95% CI, 0.36-0.52; P less than .0001). Objective response rates were 4% with cabozantinib and 0.4% with placebo (P = .0086), Exelixis, makers of the drug, said in a press release.
The most common grade 3 or 4 adverse events in the patients who received cabozantinib, compared with those who received placebo, were palmar-plantar erythrodysesthesia (17% vs. 0%), hypertension (16% vs. 2%), increased aspartate aminotransferase (12% vs. 7%), fatigue (10% vs. 4%), and diarrhea (10% vs. 2%). Treatment-related grade 5 adverse events occurred in six patients in the cabozantinib group (hepatic failure, esophagobronchial fistula, portal vein thrombosis, upper gastrointestinal hemorrhage, pulmonary embolism, and hepatorenal syndrome) and in one patient in the placebo group (hepatic failure).
Cabozantinib is also approved to treat renal cell carcinoma and medullary thyroid cancer.
Checkpoint inhibitor pembrolizumab was granted accelerated approval for the same HCC indication – to treat patients who have been previously treated with sorafenib – in late 2018.
Exelixis and its partner Ipsen have launched a phase 3 trial of cabozantinib in combination with the checkpoint inhibitor atezolizumab versus sorafenib in previously untreated advanced HCC. The trial will also explore single-agent activity of cabozantinib in the first-line setting, the company said in the press release.
The Food and Drug Administration has approved cabozantinib tablets (Cabometyx) for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.
Approval was based on an improvement in overall survival over placebo seen in the phase 3 CELESTIAL trial for patients with advanced HCC who received prior sorafenib.
Median overall survival was 10.2 months with cabozantinib versus 8.0 months with placebo (hazard ratio, 0.76; 95% confidence interval, 0.63-0.92; P = .0049). Median progression-free survival was 5.2 months with cabozantinib and 1.9 months with placebo (HR, 0.44; 95% CI, 0.36-0.52; P less than .0001). Objective response rates were 4% with cabozantinib and 0.4% with placebo (P = .0086), Exelixis, makers of the drug, said in a press release.
The most common grade 3 or 4 adverse events in the patients who received cabozantinib, compared with those who received placebo, were palmar-plantar erythrodysesthesia (17% vs. 0%), hypertension (16% vs. 2%), increased aspartate aminotransferase (12% vs. 7%), fatigue (10% vs. 4%), and diarrhea (10% vs. 2%). Treatment-related grade 5 adverse events occurred in six patients in the cabozantinib group (hepatic failure, esophagobronchial fistula, portal vein thrombosis, upper gastrointestinal hemorrhage, pulmonary embolism, and hepatorenal syndrome) and in one patient in the placebo group (hepatic failure).
Cabozantinib is also approved to treat renal cell carcinoma and medullary thyroid cancer.
Checkpoint inhibitor pembrolizumab was granted accelerated approval for the same HCC indication – to treat patients who have been previously treated with sorafenib – in late 2018.
Exelixis and its partner Ipsen have launched a phase 3 trial of cabozantinib in combination with the checkpoint inhibitor atezolizumab versus sorafenib in previously untreated advanced HCC. The trial will also explore single-agent activity of cabozantinib in the first-line setting, the company said in the press release.
Torrent Pharmaceuticals expands losartan recall
Torrent Pharmaceuticals is expanding its recall of losartan potassium tablets from 2 lots to 12 lots, according to a Safety Alert from the Food and Drug Administration.
The recall was based on the discovery of N-nitrosodiethylamine (NDEA) above recommended levels in seven 100-mg lots of losartan, four 50-mg lots, and one 25-mg lot. NDEA is a naturally occurring substance that has been classified as a probable human carcinogen by the International Agency for Research on Cancer. Torrent Pharmaceuticals has not reported any adverse events related to the recall.
Losartan currently is indicated to treat hypertension, hypertensive patients with left ventricular hypertrophy, and nephropathy in type 2 diabetic patients. Patients who are taking losartan should continue to do so, as stopping treatment without an alternative could represent a greater health risk.
“Patients should contact their pharmacist or physician who can advise them about an alternative treatment prior to returning their medication,” the FDA said in the press release.
Find the full press release on the FDA website.
Torrent Pharmaceuticals is expanding its recall of losartan potassium tablets from 2 lots to 12 lots, according to a Safety Alert from the Food and Drug Administration.
The recall was based on the discovery of N-nitrosodiethylamine (NDEA) above recommended levels in seven 100-mg lots of losartan, four 50-mg lots, and one 25-mg lot. NDEA is a naturally occurring substance that has been classified as a probable human carcinogen by the International Agency for Research on Cancer. Torrent Pharmaceuticals has not reported any adverse events related to the recall.
Losartan currently is indicated to treat hypertension, hypertensive patients with left ventricular hypertrophy, and nephropathy in type 2 diabetic patients. Patients who are taking losartan should continue to do so, as stopping treatment without an alternative could represent a greater health risk.
“Patients should contact their pharmacist or physician who can advise them about an alternative treatment prior to returning their medication,” the FDA said in the press release.
Find the full press release on the FDA website.
Torrent Pharmaceuticals is expanding its recall of losartan potassium tablets from 2 lots to 12 lots, according to a Safety Alert from the Food and Drug Administration.
The recall was based on the discovery of N-nitrosodiethylamine (NDEA) above recommended levels in seven 100-mg lots of losartan, four 50-mg lots, and one 25-mg lot. NDEA is a naturally occurring substance that has been classified as a probable human carcinogen by the International Agency for Research on Cancer. Torrent Pharmaceuticals has not reported any adverse events related to the recall.
Losartan currently is indicated to treat hypertension, hypertensive patients with left ventricular hypertrophy, and nephropathy in type 2 diabetic patients. Patients who are taking losartan should continue to do so, as stopping treatment without an alternative could represent a greater health risk.
“Patients should contact their pharmacist or physician who can advise them about an alternative treatment prior to returning their medication,” the FDA said in the press release.
Find the full press release on the FDA website.
Sickle cell infusion gains FDA breakthrough designation
The in patients with sickle cell disease of all genotypes.
The designation allows the treatment to be reviewed on an expedited schedule.
Crizanlizumab, marketed by Novartis, is a humanized anti–P-selectin monoclonal antibody that has been shown to inhibit interactions between endothelial cells, platelets, red blood cells, sickled red blood cells, and leukocytes.
In the phase 2 SUSTAIN trial, crizanlizumab reduced the median annual rate of vasoocclusive crises that resulted in health care visits by about 45%, compared with placebo (1.63 vs. 2.98; P = .010). The drug also increased the percentage of patients who did not experience any vasoocclusive crises, compared with placebo (35.8% vs. 16.9%; P = .010).
The rates of treatment-emergent and serious adverse events was similar in the drug and placebo arms of the trial.
The in patients with sickle cell disease of all genotypes.
The designation allows the treatment to be reviewed on an expedited schedule.
Crizanlizumab, marketed by Novartis, is a humanized anti–P-selectin monoclonal antibody that has been shown to inhibit interactions between endothelial cells, platelets, red blood cells, sickled red blood cells, and leukocytes.
In the phase 2 SUSTAIN trial, crizanlizumab reduced the median annual rate of vasoocclusive crises that resulted in health care visits by about 45%, compared with placebo (1.63 vs. 2.98; P = .010). The drug also increased the percentage of patients who did not experience any vasoocclusive crises, compared with placebo (35.8% vs. 16.9%; P = .010).
The rates of treatment-emergent and serious adverse events was similar in the drug and placebo arms of the trial.
The in patients with sickle cell disease of all genotypes.
The designation allows the treatment to be reviewed on an expedited schedule.
Crizanlizumab, marketed by Novartis, is a humanized anti–P-selectin monoclonal antibody that has been shown to inhibit interactions between endothelial cells, platelets, red blood cells, sickled red blood cells, and leukocytes.
In the phase 2 SUSTAIN trial, crizanlizumab reduced the median annual rate of vasoocclusive crises that resulted in health care visits by about 45%, compared with placebo (1.63 vs. 2.98; P = .010). The drug also increased the percentage of patients who did not experience any vasoocclusive crises, compared with placebo (35.8% vs. 16.9%; P = .010).
The rates of treatment-emergent and serious adverse events was similar in the drug and placebo arms of the trial.
Puppy bite at yoga retreat leads to rabies death: Prompts health warning
Individuals going to rabies-endemic countries should have a pretrip consultation with a travel health specialist, say authors of a case report describing the death of a woman who sustained a bite from a rabid puppy during a 2017 yoga retreat in rural India.
Preexposure prophylaxis is warranted, especially for individuals expected to be in those countries for long durations, those planning to go to remote areas, or if they plan activities that may put them at risk for rabies exposure, the authors wrote in Morbidity and Mortality Weekly Report.
“In the case of the yoga retreat tour, given the extended length of the tour and the rural and community activities involved, pretravel rabies vaccination should have been considered,” said Julia Murphy, DVM, a veterinarian with the Virginia Department of Health, and her coauthors in the recently published report.
The case also underscores the importance of prompt rabies diagnosis, according to Dr. Murphy and her colleagues: 250 health care workers were assessed for exposure to the patient, 72 (29%) of whom were advised to initiate postexposure prophylaxis and were treated at a cost of nearly a quarter million dollars.
The Virginia woman described in the case report was aged 65 years and had no preexisting health conditions. She had spent more than 2 months on a yoga retreat tour in India and was bitten by a puppy near her hotel in Rishikesh in northern India, according to results of a public health investigation.
That retreat ended on April 7, 2017, according to the report, and on May 3, 2017, the woman started to have pain and paresthesia in her right arm during gardening.
On May 6, she sought care at an urgent care facility, resulting in a diagnosis of carpal tunnel syndrome and a prescription for an NSAID.
The next day, she was evaluated at a hospital for anxiety, insomnia, shortness of breath, and difficulty swallowing water and was given lorazepam for a presumed panic attack. She was discharged and, in her car, experienced claustrophobia and shortness of breath. She returned to the hospital’s ED, received more lorazepam, and was again discharged.
The day after that, she was transported by ambulance to another hospital with increased anxiety, shortness of breath, chest discomfort, and progressive paresthesia; she was found to have elevated cardiac enzymes and underwent emergency cardiac catheterization, which revealed normal arteries.
That evening, the patient became “progressively agitated and combative,” according to the report, and was found to be gasping for air while trying to drink water. When family were questioned about animal exposures, the woman’s husband indicated that she had been bitten on the right hand by a puppy during the yoga retreat, about 6 weeks before the symptoms started.
Once a diagnosis of rabies was confirmed, the woman was started on aggressive treatment but eventually died, according to Dr. Murphy and her coauthors, which made this patient the ninth person in the United States to die from rabies exposure while overseas since 2008. Canine rabies has been eliminated in the United States because of the strict vaccination laws.
“These events underscore the importance of obtaining a thorough pretravel health consultation, particularly when visiting countries with high incidence of emerging or zoonotic pathogens, to ensure awareness of health risks and appropriate pretravel and postexposure health care actions,” they concluded in their report.
Dr. Murphy and her coauthors reported no potential conflicts of interest related to the case report.
SOURCE: Murphy J et al. MMWR Morb Mortal Wkly Rep. 2019 Jan 4;67(5152):1410-4.
Individuals going to rabies-endemic countries should have a pretrip consultation with a travel health specialist, say authors of a case report describing the death of a woman who sustained a bite from a rabid puppy during a 2017 yoga retreat in rural India.
Preexposure prophylaxis is warranted, especially for individuals expected to be in those countries for long durations, those planning to go to remote areas, or if they plan activities that may put them at risk for rabies exposure, the authors wrote in Morbidity and Mortality Weekly Report.
“In the case of the yoga retreat tour, given the extended length of the tour and the rural and community activities involved, pretravel rabies vaccination should have been considered,” said Julia Murphy, DVM, a veterinarian with the Virginia Department of Health, and her coauthors in the recently published report.
The case also underscores the importance of prompt rabies diagnosis, according to Dr. Murphy and her colleagues: 250 health care workers were assessed for exposure to the patient, 72 (29%) of whom were advised to initiate postexposure prophylaxis and were treated at a cost of nearly a quarter million dollars.
The Virginia woman described in the case report was aged 65 years and had no preexisting health conditions. She had spent more than 2 months on a yoga retreat tour in India and was bitten by a puppy near her hotel in Rishikesh in northern India, according to results of a public health investigation.
That retreat ended on April 7, 2017, according to the report, and on May 3, 2017, the woman started to have pain and paresthesia in her right arm during gardening.
On May 6, she sought care at an urgent care facility, resulting in a diagnosis of carpal tunnel syndrome and a prescription for an NSAID.
The next day, she was evaluated at a hospital for anxiety, insomnia, shortness of breath, and difficulty swallowing water and was given lorazepam for a presumed panic attack. She was discharged and, in her car, experienced claustrophobia and shortness of breath. She returned to the hospital’s ED, received more lorazepam, and was again discharged.
The day after that, she was transported by ambulance to another hospital with increased anxiety, shortness of breath, chest discomfort, and progressive paresthesia; she was found to have elevated cardiac enzymes and underwent emergency cardiac catheterization, which revealed normal arteries.
That evening, the patient became “progressively agitated and combative,” according to the report, and was found to be gasping for air while trying to drink water. When family were questioned about animal exposures, the woman’s husband indicated that she had been bitten on the right hand by a puppy during the yoga retreat, about 6 weeks before the symptoms started.
Once a diagnosis of rabies was confirmed, the woman was started on aggressive treatment but eventually died, according to Dr. Murphy and her coauthors, which made this patient the ninth person in the United States to die from rabies exposure while overseas since 2008. Canine rabies has been eliminated in the United States because of the strict vaccination laws.
“These events underscore the importance of obtaining a thorough pretravel health consultation, particularly when visiting countries with high incidence of emerging or zoonotic pathogens, to ensure awareness of health risks and appropriate pretravel and postexposure health care actions,” they concluded in their report.
Dr. Murphy and her coauthors reported no potential conflicts of interest related to the case report.
SOURCE: Murphy J et al. MMWR Morb Mortal Wkly Rep. 2019 Jan 4;67(5152):1410-4.
Individuals going to rabies-endemic countries should have a pretrip consultation with a travel health specialist, say authors of a case report describing the death of a woman who sustained a bite from a rabid puppy during a 2017 yoga retreat in rural India.
Preexposure prophylaxis is warranted, especially for individuals expected to be in those countries for long durations, those planning to go to remote areas, or if they plan activities that may put them at risk for rabies exposure, the authors wrote in Morbidity and Mortality Weekly Report.
“In the case of the yoga retreat tour, given the extended length of the tour and the rural and community activities involved, pretravel rabies vaccination should have been considered,” said Julia Murphy, DVM, a veterinarian with the Virginia Department of Health, and her coauthors in the recently published report.
The case also underscores the importance of prompt rabies diagnosis, according to Dr. Murphy and her colleagues: 250 health care workers were assessed for exposure to the patient, 72 (29%) of whom were advised to initiate postexposure prophylaxis and were treated at a cost of nearly a quarter million dollars.
The Virginia woman described in the case report was aged 65 years and had no preexisting health conditions. She had spent more than 2 months on a yoga retreat tour in India and was bitten by a puppy near her hotel in Rishikesh in northern India, according to results of a public health investigation.
That retreat ended on April 7, 2017, according to the report, and on May 3, 2017, the woman started to have pain and paresthesia in her right arm during gardening.
On May 6, she sought care at an urgent care facility, resulting in a diagnosis of carpal tunnel syndrome and a prescription for an NSAID.
The next day, she was evaluated at a hospital for anxiety, insomnia, shortness of breath, and difficulty swallowing water and was given lorazepam for a presumed panic attack. She was discharged and, in her car, experienced claustrophobia and shortness of breath. She returned to the hospital’s ED, received more lorazepam, and was again discharged.
The day after that, she was transported by ambulance to another hospital with increased anxiety, shortness of breath, chest discomfort, and progressive paresthesia; she was found to have elevated cardiac enzymes and underwent emergency cardiac catheterization, which revealed normal arteries.
That evening, the patient became “progressively agitated and combative,” according to the report, and was found to be gasping for air while trying to drink water. When family were questioned about animal exposures, the woman’s husband indicated that she had been bitten on the right hand by a puppy during the yoga retreat, about 6 weeks before the symptoms started.
Once a diagnosis of rabies was confirmed, the woman was started on aggressive treatment but eventually died, according to Dr. Murphy and her coauthors, which made this patient the ninth person in the United States to die from rabies exposure while overseas since 2008. Canine rabies has been eliminated in the United States because of the strict vaccination laws.
“These events underscore the importance of obtaining a thorough pretravel health consultation, particularly when visiting countries with high incidence of emerging or zoonotic pathogens, to ensure awareness of health risks and appropriate pretravel and postexposure health care actions,” they concluded in their report.
Dr. Murphy and her coauthors reported no potential conflicts of interest related to the case report.
SOURCE: Murphy J et al. MMWR Morb Mortal Wkly Rep. 2019 Jan 4;67(5152):1410-4.
FROM MMWR
Key clinical point: depending on length of trip, location, and activities involved.
Major finding: A Virginia woman died after sustaining a bite from a rabid puppy during a 2017 yoga retreat in rural India.
Study details: Case report including details of the 65-year-old woman’s trip, rabies exposure, symptoms, diagnosis, and eventual death.
Disclosures: Authors reported no potential conflicts of interest.
Source: Murphy J et al. MMWR Morb Mortal Wkly Rep. 2019 Jan 4;67(5152):1410-4.
FDA approves new ALL treatment for children, young adults
The in pediatric and young adult patients aged 1 month to 21 years.
Calaspargase pegol-mknl is an asparagine-specific enzyme intended to provide a longer interval between doses, compared with other available pegaspargase products. The recommended dosage of calaspargase pegol-mknl is 2,500 units/m2 given no more frequently than every 21 days.
The FDA said it approved calaspargase pegol-mknl because the drug maintained nadir serum asparaginase activity above the level of 0.1 U/mL when given at 2,500 U/m2 every 3 weeks.
Calaspargase pegol-mknl was evaluated in Study DFCI 11-001, a trial of 237 children and adolescents with newly diagnosed ALL or lymphoblastic lymphoma. The patients’ median age was 5 years.
Study participants received calaspargase pegol-mknl at 2,500 U/m2 (n = 118) or pegaspargase at 2,500 U/m2 (n = 119) as part of a Dana-Farber Cancer Institute ALL Consortium backbone therapy. The median duration of exposure was 8 months for both calaspargase pegol-mknl and pegaspargase. Among the patients with B-cell lineage ALL, the complete remission rate was 98% in the calaspargase pegol-mknl arm and 99% in the pegaspargase arm. Estimated overall survival rates were comparable between the arms.
Common grade 3 or higher adverse events in the calaspargase pegol-mknl and pegaspargase arms included elevated transaminase (52% and 66%, respectively), bilirubin increase (20% and 25%), pancreatitis (18% and 24%), and abnormal clotting studies (14% and 21%). There was one fatal adverse event among patients on calaspargase pegol-mknl – multiorgan failure in the setting of chronic pancreatitis associated with a pancreatic pseudocyst.
The safety of calaspargase pegol-mknl was also evaluated in Study AALL07P4, a trial of patients with newly diagnosed, high-risk B-precursor ALL. The patients received calaspargase pegol-mknl at 2,500 U/m2 (n = 43) or 2,100 U/m2 (n = 68) or pegaspargase at 2,500 U/m2 (n = 52) as a component of an augmented Berlin-Frankfurt-Münster regimen. The patients’ median age was 11 years. The median duration of exposure was 7 months for both calaspargase pegol-mknl and pegaspargase. There were 3 induction deaths among the 111 patients who received calaspargase pegol-mknl (2.8%) but no induction deaths among the 52 patients treated with pegaspargase.
Additional details on these studies and calaspargase pegol-mknl can be found in the drug’s prescribing information. Calaspargase pegol-mknl is a product of Servier.
The in pediatric and young adult patients aged 1 month to 21 years.
Calaspargase pegol-mknl is an asparagine-specific enzyme intended to provide a longer interval between doses, compared with other available pegaspargase products. The recommended dosage of calaspargase pegol-mknl is 2,500 units/m2 given no more frequently than every 21 days.
The FDA said it approved calaspargase pegol-mknl because the drug maintained nadir serum asparaginase activity above the level of 0.1 U/mL when given at 2,500 U/m2 every 3 weeks.
Calaspargase pegol-mknl was evaluated in Study DFCI 11-001, a trial of 237 children and adolescents with newly diagnosed ALL or lymphoblastic lymphoma. The patients’ median age was 5 years.
Study participants received calaspargase pegol-mknl at 2,500 U/m2 (n = 118) or pegaspargase at 2,500 U/m2 (n = 119) as part of a Dana-Farber Cancer Institute ALL Consortium backbone therapy. The median duration of exposure was 8 months for both calaspargase pegol-mknl and pegaspargase. Among the patients with B-cell lineage ALL, the complete remission rate was 98% in the calaspargase pegol-mknl arm and 99% in the pegaspargase arm. Estimated overall survival rates were comparable between the arms.
Common grade 3 or higher adverse events in the calaspargase pegol-mknl and pegaspargase arms included elevated transaminase (52% and 66%, respectively), bilirubin increase (20% and 25%), pancreatitis (18% and 24%), and abnormal clotting studies (14% and 21%). There was one fatal adverse event among patients on calaspargase pegol-mknl – multiorgan failure in the setting of chronic pancreatitis associated with a pancreatic pseudocyst.
The safety of calaspargase pegol-mknl was also evaluated in Study AALL07P4, a trial of patients with newly diagnosed, high-risk B-precursor ALL. The patients received calaspargase pegol-mknl at 2,500 U/m2 (n = 43) or 2,100 U/m2 (n = 68) or pegaspargase at 2,500 U/m2 (n = 52) as a component of an augmented Berlin-Frankfurt-Münster regimen. The patients’ median age was 11 years. The median duration of exposure was 7 months for both calaspargase pegol-mknl and pegaspargase. There were 3 induction deaths among the 111 patients who received calaspargase pegol-mknl (2.8%) but no induction deaths among the 52 patients treated with pegaspargase.
Additional details on these studies and calaspargase pegol-mknl can be found in the drug’s prescribing information. Calaspargase pegol-mknl is a product of Servier.
The in pediatric and young adult patients aged 1 month to 21 years.
Calaspargase pegol-mknl is an asparagine-specific enzyme intended to provide a longer interval between doses, compared with other available pegaspargase products. The recommended dosage of calaspargase pegol-mknl is 2,500 units/m2 given no more frequently than every 21 days.
The FDA said it approved calaspargase pegol-mknl because the drug maintained nadir serum asparaginase activity above the level of 0.1 U/mL when given at 2,500 U/m2 every 3 weeks.
Calaspargase pegol-mknl was evaluated in Study DFCI 11-001, a trial of 237 children and adolescents with newly diagnosed ALL or lymphoblastic lymphoma. The patients’ median age was 5 years.
Study participants received calaspargase pegol-mknl at 2,500 U/m2 (n = 118) or pegaspargase at 2,500 U/m2 (n = 119) as part of a Dana-Farber Cancer Institute ALL Consortium backbone therapy. The median duration of exposure was 8 months for both calaspargase pegol-mknl and pegaspargase. Among the patients with B-cell lineage ALL, the complete remission rate was 98% in the calaspargase pegol-mknl arm and 99% in the pegaspargase arm. Estimated overall survival rates were comparable between the arms.
Common grade 3 or higher adverse events in the calaspargase pegol-mknl and pegaspargase arms included elevated transaminase (52% and 66%, respectively), bilirubin increase (20% and 25%), pancreatitis (18% and 24%), and abnormal clotting studies (14% and 21%). There was one fatal adverse event among patients on calaspargase pegol-mknl – multiorgan failure in the setting of chronic pancreatitis associated with a pancreatic pseudocyst.
The safety of calaspargase pegol-mknl was also evaluated in Study AALL07P4, a trial of patients with newly diagnosed, high-risk B-precursor ALL. The patients received calaspargase pegol-mknl at 2,500 U/m2 (n = 43) or 2,100 U/m2 (n = 68) or pegaspargase at 2,500 U/m2 (n = 52) as a component of an augmented Berlin-Frankfurt-Münster regimen. The patients’ median age was 11 years. The median duration of exposure was 7 months for both calaspargase pegol-mknl and pegaspargase. There were 3 induction deaths among the 111 patients who received calaspargase pegol-mknl (2.8%) but no induction deaths among the 52 patients treated with pegaspargase.
Additional details on these studies and calaspargase pegol-mknl can be found in the drug’s prescribing information. Calaspargase pegol-mknl is a product of Servier.
Synthetic opioids drive spike in U.S. fatal drug overdoses
New federal statistics suggest that the opioid epidemic in the United States is evolving as physicians crack down on the use of prescription painkillers: Fatal drug overdose deaths rose by 12% from 2016 to 2017, boosted by a wave of fatalities linked to illicit synthetic opioids like fentanyl that are now linked to an estimated 60% of opioid-related deaths.
“Overall, the overdose epidemic continues to worsen, and it has grown increasingly complex by coinvolvement of prescription and illicit drugs,” Lawrence Scholl, PhD, MPH, and his associates at the Centers for Disease Control & Prevention wrote in the Morbidity and Mortality Weekly Report.
The new statistics provide more evidence that 2017 marked “a sharp increase in what has characterized as the third wave of the opioid epidemic,” said drug and health policy researcher Stephen Crystal, PhD, of Rutgers University, New Brunswick, N.J., in an interview. He was referring to a wave that experts believe started in 2013 amid a spike in U.S. overdose deaths from fentanyl and other synthetic opioids.
The new report analyzes fatal drug overdose data from 2013 to 2017. According to the findings, the total number of those overdoses rose to 70,237 in 2017, up from 63,632 in 2016. The highest drug overdose death rates in 2017 were in West Virginia, followed by Ohio, Pennsylvania, and the District of Columbia.
Some statistics did not change much from 2016 to 2017: About two-thirds of the drug overdose deaths were linked to opioids in both years, and the death rate of cases linked to prescription drugs and heroin remained steady. (Death rates in the report were age adjusted.)
However, the percentage of fatal overdose cases linked to synthetic opioids grew 45% from 2016 to 2017. Overall, 60% of opioid-related fatal overdoses in 2017 involved synthetic opioids.
The report identifies increases in several areas from 2016 to 2017. Opioid-related drug overdose deaths among black people rose by 25%, and an analysis of data from 34 states and the District of Columbia found the highest increases in death rates in North Carolina (29%), Ohio (19%), and Maine (19%).
In regard to deaths linked to synthetic opioids specifically, the highest death rates in 2017 were in West Virginia (37 per 100,000), Ohio (32 per 100,000), and New Hampshire (30 per 100,000).
“Part of what we’re seeing in these increased numbers are individuals who have pain, can’t get prescribed opioids, and turn to street drugs,” Dr. Crystal said, adding that “abruptly cutting patients off is not good, and leaving patients with a lot of untreated pain is not good. If people are going to be discontinued [from opioids] or have their doses reduced, the taper needs to be done very slowly and carefully.”
Synthetic opioids were not the only drugs that are driving up fatal overdoses, as the death rates of cases linked to cocaine and psychostimulants (such as methamphetamine) jumped by more than a third in 2017.
“The most important thing these numbers are telling me is that it’s becoming more and more attractive to drug dealers to put fentanyl in the heroin, cocaine, and other drugs they sell,” Dr. Crystal said. “When that happens, dependence on street drugs becomes much more deadly. It’s almost impossible to get the dose right. Every time you shoot up, you’re taking a chance that you’ll overdose.”
The report had limitations, including the fact that details about drug use were missing from 12% (2016) and 15% (2017) of death certificates in fatal overdose cases. By state, the percentages of those death certificates that included drug information ranged from as little as 55% to 99%.
There’s some possible positive news: The report points to preliminary data from 2018 suggesting that the number of annual drug overdose deaths may be leveling off – although it says more analysis is needed to confirm the trend.
Dr. Crystal, however, is not celebrating. “I don’t see this as a good news story, really,” he said, adding that there’s “a little too much of people patting themselves on the back” because they’re proud of cutbacks in opioid prescriptions.
“This doesn’t have to do with the huge number of people who got started with opioids years ago” and are now at risk of using street drugs, he said. “We haven’t engaged that population at the rate we need to. And flattening out at 70,000 drug overdoses a year is not a good news story.”
Dr. Crystal reported no relevant disclosures.
SOURCE: Scholl L et al. MMWR. 2019 Jan 4;67(5152):1419-27.
New federal statistics suggest that the opioid epidemic in the United States is evolving as physicians crack down on the use of prescription painkillers: Fatal drug overdose deaths rose by 12% from 2016 to 2017, boosted by a wave of fatalities linked to illicit synthetic opioids like fentanyl that are now linked to an estimated 60% of opioid-related deaths.
“Overall, the overdose epidemic continues to worsen, and it has grown increasingly complex by coinvolvement of prescription and illicit drugs,” Lawrence Scholl, PhD, MPH, and his associates at the Centers for Disease Control & Prevention wrote in the Morbidity and Mortality Weekly Report.
The new statistics provide more evidence that 2017 marked “a sharp increase in what has characterized as the third wave of the opioid epidemic,” said drug and health policy researcher Stephen Crystal, PhD, of Rutgers University, New Brunswick, N.J., in an interview. He was referring to a wave that experts believe started in 2013 amid a spike in U.S. overdose deaths from fentanyl and other synthetic opioids.
The new report analyzes fatal drug overdose data from 2013 to 2017. According to the findings, the total number of those overdoses rose to 70,237 in 2017, up from 63,632 in 2016. The highest drug overdose death rates in 2017 were in West Virginia, followed by Ohio, Pennsylvania, and the District of Columbia.
Some statistics did not change much from 2016 to 2017: About two-thirds of the drug overdose deaths were linked to opioids in both years, and the death rate of cases linked to prescription drugs and heroin remained steady. (Death rates in the report were age adjusted.)
However, the percentage of fatal overdose cases linked to synthetic opioids grew 45% from 2016 to 2017. Overall, 60% of opioid-related fatal overdoses in 2017 involved synthetic opioids.
The report identifies increases in several areas from 2016 to 2017. Opioid-related drug overdose deaths among black people rose by 25%, and an analysis of data from 34 states and the District of Columbia found the highest increases in death rates in North Carolina (29%), Ohio (19%), and Maine (19%).
In regard to deaths linked to synthetic opioids specifically, the highest death rates in 2017 were in West Virginia (37 per 100,000), Ohio (32 per 100,000), and New Hampshire (30 per 100,000).
“Part of what we’re seeing in these increased numbers are individuals who have pain, can’t get prescribed opioids, and turn to street drugs,” Dr. Crystal said, adding that “abruptly cutting patients off is not good, and leaving patients with a lot of untreated pain is not good. If people are going to be discontinued [from opioids] or have their doses reduced, the taper needs to be done very slowly and carefully.”
Synthetic opioids were not the only drugs that are driving up fatal overdoses, as the death rates of cases linked to cocaine and psychostimulants (such as methamphetamine) jumped by more than a third in 2017.
“The most important thing these numbers are telling me is that it’s becoming more and more attractive to drug dealers to put fentanyl in the heroin, cocaine, and other drugs they sell,” Dr. Crystal said. “When that happens, dependence on street drugs becomes much more deadly. It’s almost impossible to get the dose right. Every time you shoot up, you’re taking a chance that you’ll overdose.”
The report had limitations, including the fact that details about drug use were missing from 12% (2016) and 15% (2017) of death certificates in fatal overdose cases. By state, the percentages of those death certificates that included drug information ranged from as little as 55% to 99%.
There’s some possible positive news: The report points to preliminary data from 2018 suggesting that the number of annual drug overdose deaths may be leveling off – although it says more analysis is needed to confirm the trend.
Dr. Crystal, however, is not celebrating. “I don’t see this as a good news story, really,” he said, adding that there’s “a little too much of people patting themselves on the back” because they’re proud of cutbacks in opioid prescriptions.
“This doesn’t have to do with the huge number of people who got started with opioids years ago” and are now at risk of using street drugs, he said. “We haven’t engaged that population at the rate we need to. And flattening out at 70,000 drug overdoses a year is not a good news story.”
Dr. Crystal reported no relevant disclosures.
SOURCE: Scholl L et al. MMWR. 2019 Jan 4;67(5152):1419-27.
New federal statistics suggest that the opioid epidemic in the United States is evolving as physicians crack down on the use of prescription painkillers: Fatal drug overdose deaths rose by 12% from 2016 to 2017, boosted by a wave of fatalities linked to illicit synthetic opioids like fentanyl that are now linked to an estimated 60% of opioid-related deaths.
“Overall, the overdose epidemic continues to worsen, and it has grown increasingly complex by coinvolvement of prescription and illicit drugs,” Lawrence Scholl, PhD, MPH, and his associates at the Centers for Disease Control & Prevention wrote in the Morbidity and Mortality Weekly Report.
The new statistics provide more evidence that 2017 marked “a sharp increase in what has characterized as the third wave of the opioid epidemic,” said drug and health policy researcher Stephen Crystal, PhD, of Rutgers University, New Brunswick, N.J., in an interview. He was referring to a wave that experts believe started in 2013 amid a spike in U.S. overdose deaths from fentanyl and other synthetic opioids.
The new report analyzes fatal drug overdose data from 2013 to 2017. According to the findings, the total number of those overdoses rose to 70,237 in 2017, up from 63,632 in 2016. The highest drug overdose death rates in 2017 were in West Virginia, followed by Ohio, Pennsylvania, and the District of Columbia.
Some statistics did not change much from 2016 to 2017: About two-thirds of the drug overdose deaths were linked to opioids in both years, and the death rate of cases linked to prescription drugs and heroin remained steady. (Death rates in the report were age adjusted.)
However, the percentage of fatal overdose cases linked to synthetic opioids grew 45% from 2016 to 2017. Overall, 60% of opioid-related fatal overdoses in 2017 involved synthetic opioids.
The report identifies increases in several areas from 2016 to 2017. Opioid-related drug overdose deaths among black people rose by 25%, and an analysis of data from 34 states and the District of Columbia found the highest increases in death rates in North Carolina (29%), Ohio (19%), and Maine (19%).
In regard to deaths linked to synthetic opioids specifically, the highest death rates in 2017 were in West Virginia (37 per 100,000), Ohio (32 per 100,000), and New Hampshire (30 per 100,000).
“Part of what we’re seeing in these increased numbers are individuals who have pain, can’t get prescribed opioids, and turn to street drugs,” Dr. Crystal said, adding that “abruptly cutting patients off is not good, and leaving patients with a lot of untreated pain is not good. If people are going to be discontinued [from opioids] or have their doses reduced, the taper needs to be done very slowly and carefully.”
Synthetic opioids were not the only drugs that are driving up fatal overdoses, as the death rates of cases linked to cocaine and psychostimulants (such as methamphetamine) jumped by more than a third in 2017.
“The most important thing these numbers are telling me is that it’s becoming more and more attractive to drug dealers to put fentanyl in the heroin, cocaine, and other drugs they sell,” Dr. Crystal said. “When that happens, dependence on street drugs becomes much more deadly. It’s almost impossible to get the dose right. Every time you shoot up, you’re taking a chance that you’ll overdose.”
The report had limitations, including the fact that details about drug use were missing from 12% (2016) and 15% (2017) of death certificates in fatal overdose cases. By state, the percentages of those death certificates that included drug information ranged from as little as 55% to 99%.
There’s some possible positive news: The report points to preliminary data from 2018 suggesting that the number of annual drug overdose deaths may be leveling off – although it says more analysis is needed to confirm the trend.
Dr. Crystal, however, is not celebrating. “I don’t see this as a good news story, really,” he said, adding that there’s “a little too much of people patting themselves on the back” because they’re proud of cutbacks in opioid prescriptions.
“This doesn’t have to do with the huge number of people who got started with opioids years ago” and are now at risk of using street drugs, he said. “We haven’t engaged that population at the rate we need to. And flattening out at 70,000 drug overdoses a year is not a good news story.”
Dr. Crystal reported no relevant disclosures.
SOURCE: Scholl L et al. MMWR. 2019 Jan 4;67(5152):1419-27.
FROM MMWR