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Christopher Palmer has been an associate editor at MDedge News since 2017. When he's not tidying grammar, he writes short pieces about breaking FDA announcements and approvals, as well as journal articles. He proudly holds a BA in English and philosophy. Follow him on Twitter @cmacmpalm.
FDA approves second drug for thrombocytopenia in liver disease
The Food and Drug Administration has approved lusutrombopag (Mulpleta) for the treatment of thrombocytopenia in patients with chronic liver disease who are scheduled to undergo medical or dental procedures. The drug is expected to be available in the United States in September 2018.
In May 2018, the FDA approved avatrombopag (Doptelet) as the first treatment for thrombocytopenia in this patient population.
The approval is based on a pair of phase 3, double-blind, placebo-controlled clinical trials – L-PLUS 1 and L-PLUS 2 (NCT02389621) – that included 312 patients who have chronic liver disease with severe thrombocytopenia. In L-PLUS 1, the primary endpoint was the percentage of patients who didn’t need platelet transfusions before the primary procedure was performed; this was met by 78% in the lusutrombopag group versus just 13% in the control group. In L-PLUS 2, the primary endpoint was the percentage of patients who didn’t need platelet transfusions before the procedure and didn’t require rescue therapy from randomization through 7 days post procedure; this was met by 65% of patients the lusutrombopag group versus 29% of patients the control group.
The most common adverse event was headache, and the recommended dosage for lusutrombopag is 3 mg orally once daily with or without food for 7 days. Lusutrombopag is not indicated for general platelet normalization in patients with chronic liver disease and thrombocytopenia. Full prescribing information and further information about the approval can be found on the FDA website.
Lusutrombopag was approved in Japan in 2015 for this indication and is slated to be evaluated by the European Medicines Agency in 2019. The drug is marketed by Shionogi.
The Food and Drug Administration has approved lusutrombopag (Mulpleta) for the treatment of thrombocytopenia in patients with chronic liver disease who are scheduled to undergo medical or dental procedures. The drug is expected to be available in the United States in September 2018.
In May 2018, the FDA approved avatrombopag (Doptelet) as the first treatment for thrombocytopenia in this patient population.
The approval is based on a pair of phase 3, double-blind, placebo-controlled clinical trials – L-PLUS 1 and L-PLUS 2 (NCT02389621) – that included 312 patients who have chronic liver disease with severe thrombocytopenia. In L-PLUS 1, the primary endpoint was the percentage of patients who didn’t need platelet transfusions before the primary procedure was performed; this was met by 78% in the lusutrombopag group versus just 13% in the control group. In L-PLUS 2, the primary endpoint was the percentage of patients who didn’t need platelet transfusions before the procedure and didn’t require rescue therapy from randomization through 7 days post procedure; this was met by 65% of patients the lusutrombopag group versus 29% of patients the control group.
The most common adverse event was headache, and the recommended dosage for lusutrombopag is 3 mg orally once daily with or without food for 7 days. Lusutrombopag is not indicated for general platelet normalization in patients with chronic liver disease and thrombocytopenia. Full prescribing information and further information about the approval can be found on the FDA website.
Lusutrombopag was approved in Japan in 2015 for this indication and is slated to be evaluated by the European Medicines Agency in 2019. The drug is marketed by Shionogi.
The Food and Drug Administration has approved lusutrombopag (Mulpleta) for the treatment of thrombocytopenia in patients with chronic liver disease who are scheduled to undergo medical or dental procedures. The drug is expected to be available in the United States in September 2018.
In May 2018, the FDA approved avatrombopag (Doptelet) as the first treatment for thrombocytopenia in this patient population.
The approval is based on a pair of phase 3, double-blind, placebo-controlled clinical trials – L-PLUS 1 and L-PLUS 2 (NCT02389621) – that included 312 patients who have chronic liver disease with severe thrombocytopenia. In L-PLUS 1, the primary endpoint was the percentage of patients who didn’t need platelet transfusions before the primary procedure was performed; this was met by 78% in the lusutrombopag group versus just 13% in the control group. In L-PLUS 2, the primary endpoint was the percentage of patients who didn’t need platelet transfusions before the procedure and didn’t require rescue therapy from randomization through 7 days post procedure; this was met by 65% of patients the lusutrombopag group versus 29% of patients the control group.
The most common adverse event was headache, and the recommended dosage for lusutrombopag is 3 mg orally once daily with or without food for 7 days. Lusutrombopag is not indicated for general platelet normalization in patients with chronic liver disease and thrombocytopenia. Full prescribing information and further information about the approval can be found on the FDA website.
Lusutrombopag was approved in Japan in 2015 for this indication and is slated to be evaluated by the European Medicines Agency in 2019. The drug is marketed by Shionogi.
FDA approves Perseris for schizophrenia
The Food and Drug Administration has approved Perseris, a once-monthly, long-acting injectable formulation of risperidone, for the treatment of schizophrenia in adults, according to a press release from the drug’s developer, Indivior.
The depot formulation of the atypical antipsychotic, administered subcutaneously, provides sustained levels of risperidone for 1 month; the process of injecting it also releases some of the drug, which helps achieve peak plasma levels within the first 4-6 hours. There is no need for either loading doses or supplemental oral doses with Perseris.
Efficacy was based on a phase 3, randomized, double-blind, placebo-controlled, 8-week study of 354 patients. The primary endpoint was improvement in Positive and Negative Syndrome Scale by day 57. Safety was evaluated in 814 patients who had participated in clinical trials of Perseris and was in line with the known safety profile of risperidone.
The most common adverse reactions, occurring in more than 5% of patients, were increased weight, sedation/somnolence, and musculoskeletal pain. Other risks included neuroleptic malignant syndrome, tardive dyskinesia, and hyperprolactinemia. Full prescribing information can be found on the manufacturer’s website.
The Food and Drug Administration has approved Perseris, a once-monthly, long-acting injectable formulation of risperidone, for the treatment of schizophrenia in adults, according to a press release from the drug’s developer, Indivior.
The depot formulation of the atypical antipsychotic, administered subcutaneously, provides sustained levels of risperidone for 1 month; the process of injecting it also releases some of the drug, which helps achieve peak plasma levels within the first 4-6 hours. There is no need for either loading doses or supplemental oral doses with Perseris.
Efficacy was based on a phase 3, randomized, double-blind, placebo-controlled, 8-week study of 354 patients. The primary endpoint was improvement in Positive and Negative Syndrome Scale by day 57. Safety was evaluated in 814 patients who had participated in clinical trials of Perseris and was in line with the known safety profile of risperidone.
The most common adverse reactions, occurring in more than 5% of patients, were increased weight, sedation/somnolence, and musculoskeletal pain. Other risks included neuroleptic malignant syndrome, tardive dyskinesia, and hyperprolactinemia. Full prescribing information can be found on the manufacturer’s website.
The Food and Drug Administration has approved Perseris, a once-monthly, long-acting injectable formulation of risperidone, for the treatment of schizophrenia in adults, according to a press release from the drug’s developer, Indivior.
The depot formulation of the atypical antipsychotic, administered subcutaneously, provides sustained levels of risperidone for 1 month; the process of injecting it also releases some of the drug, which helps achieve peak plasma levels within the first 4-6 hours. There is no need for either loading doses or supplemental oral doses with Perseris.
Efficacy was based on a phase 3, randomized, double-blind, placebo-controlled, 8-week study of 354 patients. The primary endpoint was improvement in Positive and Negative Syndrome Scale by day 57. Safety was evaluated in 814 patients who had participated in clinical trials of Perseris and was in line with the known safety profile of risperidone.
The most common adverse reactions, occurring in more than 5% of patients, were increased weight, sedation/somnolence, and musculoskeletal pain. Other risks included neuroleptic malignant syndrome, tardive dyskinesia, and hyperprolactinemia. Full prescribing information can be found on the manufacturer’s website.
FDA approves radioactive agent for adrenal tumors
(pheochromocytoma or paraganglioma) that are unresectable, have metastasized, and require systemic therapy.
This is the first FDA-approved drug for this use, the FDA said in a press announcement.
Approval is based on a single-arm, open-label clinical trial that included 68 patients. The primary endpoint was the number or patients with a 50% or greater reduction of antihypertensive medications lasting at least 6 months; the secondary endpoint was overall tumor response according to traditional imaging criteria. The primary endpoint was met by 17 patients, and the secondary endpoint was achieved in 15.
The most common severe side effects were lymphopenia, neutropenia, thrombocytopenia, fatigue, anemia, increased international normalized ratio, nausea, dizziness, hypertension, and vomiting. Furthermore, because this is a radioactive therapeutic agent, there is a warning about radiation exposure for both patients and family members, a risk that is greatest in pediatric patients.
Other warnings and precautions include a risk of myelosuppression, underactive thyroid, elevations in blood pressure, renal failure or kidney injury, and pneumonitis. Myelodysplastic syndrome and acute leukemias were observed in patients who received the radioactive agent, and the magnitude of this risk will continue to be studied, the FDA said.
The approval was granted to Progenics Pharmaceuticals.
(pheochromocytoma or paraganglioma) that are unresectable, have metastasized, and require systemic therapy.
This is the first FDA-approved drug for this use, the FDA said in a press announcement.
Approval is based on a single-arm, open-label clinical trial that included 68 patients. The primary endpoint was the number or patients with a 50% or greater reduction of antihypertensive medications lasting at least 6 months; the secondary endpoint was overall tumor response according to traditional imaging criteria. The primary endpoint was met by 17 patients, and the secondary endpoint was achieved in 15.
The most common severe side effects were lymphopenia, neutropenia, thrombocytopenia, fatigue, anemia, increased international normalized ratio, nausea, dizziness, hypertension, and vomiting. Furthermore, because this is a radioactive therapeutic agent, there is a warning about radiation exposure for both patients and family members, a risk that is greatest in pediatric patients.
Other warnings and precautions include a risk of myelosuppression, underactive thyroid, elevations in blood pressure, renal failure or kidney injury, and pneumonitis. Myelodysplastic syndrome and acute leukemias were observed in patients who received the radioactive agent, and the magnitude of this risk will continue to be studied, the FDA said.
The approval was granted to Progenics Pharmaceuticals.
(pheochromocytoma or paraganglioma) that are unresectable, have metastasized, and require systemic therapy.
This is the first FDA-approved drug for this use, the FDA said in a press announcement.
Approval is based on a single-arm, open-label clinical trial that included 68 patients. The primary endpoint was the number or patients with a 50% or greater reduction of antihypertensive medications lasting at least 6 months; the secondary endpoint was overall tumor response according to traditional imaging criteria. The primary endpoint was met by 17 patients, and the secondary endpoint was achieved in 15.
The most common severe side effects were lymphopenia, neutropenia, thrombocytopenia, fatigue, anemia, increased international normalized ratio, nausea, dizziness, hypertension, and vomiting. Furthermore, because this is a radioactive therapeutic agent, there is a warning about radiation exposure for both patients and family members, a risk that is greatest in pediatric patients.
Other warnings and precautions include a risk of myelosuppression, underactive thyroid, elevations in blood pressure, renal failure or kidney injury, and pneumonitis. Myelodysplastic syndrome and acute leukemias were observed in patients who received the radioactive agent, and the magnitude of this risk will continue to be studied, the FDA said.
The approval was granted to Progenics Pharmaceuticals.
FDA approves Orilissa for endometriosis pain
The Food and Drug Administration has approved elagolix (Orilissa) for oral treatment of moderate to severe pain associated with endometriosis, announced AbbVie and Neurocrine Biosciences; this approval makes it the first such treatment in more than a decade. It is expected to be available in the United States in early August.
Elagolix is a gonadotropin-releasing hormone (GnRH) antagonist and the first and only one developed specifically for managing this kind of pain.
The approval is based on two 6-month, randomized, double-blind, placebo-controlled phase 3 trials that compared a total of 952 adult women treated with either elagolix with 734 treated with placebo. All of the women experienced moderate to severe endometriosis pain; their ages ranged from 18 to 49 years.
Of the women in the treatment group, 475 were treated with a 150-mg daily dose, and 477 were treated with a 200-mg twice-daily dose. Both treatment groups showed significantly greater mean reductions in pain – both daily menstrual and nonmenstrual pelvic pain – at 6 months. Furthermore, women in the 200-mg twice-daily group also showed statistically significant greater reductions in pain with sex at 3 months, compared with placebo. Altogether, these represent the three most common kinds of endometriosis pain.
The most concerning adverse event associated with elagolix is dose-dependent decreases in bone mineral density; this effect limits treatment to either 150 mg daily for up to 24 months or 200 mg twice daily for up to 6 months. Bone mineral density loss might not be completely reversible, even with treatment cessation. Common adverse events (occurring in at least 5%) included hot flush/night sweats, headache, and nausea. Elagolix is not recommended for women who are or may be pregnant, have osteoporosis, have severe liver disease, or take strong OATP1B1 inhibitors.
Full prescribing information, as well as further details on the approval, can be found on the AbbVie website.
The Food and Drug Administration has approved elagolix (Orilissa) for oral treatment of moderate to severe pain associated with endometriosis, announced AbbVie and Neurocrine Biosciences; this approval makes it the first such treatment in more than a decade. It is expected to be available in the United States in early August.
Elagolix is a gonadotropin-releasing hormone (GnRH) antagonist and the first and only one developed specifically for managing this kind of pain.
The approval is based on two 6-month, randomized, double-blind, placebo-controlled phase 3 trials that compared a total of 952 adult women treated with either elagolix with 734 treated with placebo. All of the women experienced moderate to severe endometriosis pain; their ages ranged from 18 to 49 years.
Of the women in the treatment group, 475 were treated with a 150-mg daily dose, and 477 were treated with a 200-mg twice-daily dose. Both treatment groups showed significantly greater mean reductions in pain – both daily menstrual and nonmenstrual pelvic pain – at 6 months. Furthermore, women in the 200-mg twice-daily group also showed statistically significant greater reductions in pain with sex at 3 months, compared with placebo. Altogether, these represent the three most common kinds of endometriosis pain.
The most concerning adverse event associated with elagolix is dose-dependent decreases in bone mineral density; this effect limits treatment to either 150 mg daily for up to 24 months or 200 mg twice daily for up to 6 months. Bone mineral density loss might not be completely reversible, even with treatment cessation. Common adverse events (occurring in at least 5%) included hot flush/night sweats, headache, and nausea. Elagolix is not recommended for women who are or may be pregnant, have osteoporosis, have severe liver disease, or take strong OATP1B1 inhibitors.
Full prescribing information, as well as further details on the approval, can be found on the AbbVie website.
The Food and Drug Administration has approved elagolix (Orilissa) for oral treatment of moderate to severe pain associated with endometriosis, announced AbbVie and Neurocrine Biosciences; this approval makes it the first such treatment in more than a decade. It is expected to be available in the United States in early August.
Elagolix is a gonadotropin-releasing hormone (GnRH) antagonist and the first and only one developed specifically for managing this kind of pain.
The approval is based on two 6-month, randomized, double-blind, placebo-controlled phase 3 trials that compared a total of 952 adult women treated with either elagolix with 734 treated with placebo. All of the women experienced moderate to severe endometriosis pain; their ages ranged from 18 to 49 years.
Of the women in the treatment group, 475 were treated with a 150-mg daily dose, and 477 were treated with a 200-mg twice-daily dose. Both treatment groups showed significantly greater mean reductions in pain – both daily menstrual and nonmenstrual pelvic pain – at 6 months. Furthermore, women in the 200-mg twice-daily group also showed statistically significant greater reductions in pain with sex at 3 months, compared with placebo. Altogether, these represent the three most common kinds of endometriosis pain.
The most concerning adverse event associated with elagolix is dose-dependent decreases in bone mineral density; this effect limits treatment to either 150 mg daily for up to 24 months or 200 mg twice daily for up to 6 months. Bone mineral density loss might not be completely reversible, even with treatment cessation. Common adverse events (occurring in at least 5%) included hot flush/night sweats, headache, and nausea. Elagolix is not recommended for women who are or may be pregnant, have osteoporosis, have severe liver disease, or take strong OATP1B1 inhibitors.
Full prescribing information, as well as further details on the approval, can be found on the AbbVie website.
FDA approves IDH1 inhibitor for relapsed/refractory AML
The Food and Drug Administration has approved ivosidenib (Tibsovo) as the first treatment of adult patients with relapsed/refractory acute myeloid leukemia (AML) and an isocitrate dehydrogenase-1 (IDH1) mutation.
More specifically, the oral treatment has been approved for patients whose mutations have been identified by the Abbott RealTime IDH1 assay, a companion diagnostic test.
The approval was based on results from a phase 1, open-label, single-arm, multicenter, dose-escalation and expansion trial of adult patients in this AML population. The primary end point was combined complete remission and complete remission with partial hematologic improvement; this combined rate was 32.8%, and the median duration of this remission was 8.2 months.
The most serious adverse events included differentiation syndrome, QTc prolongation, and Guillain-Barré syndrome. Other adverse reactions included fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, and constipation.
Ivosidenib is marketed as Tibsovo by Agios Pharmaceuticals. The RealTime IDH1 Assay is marketed by Abbott Laboratories.
The Food and Drug Administration has approved ivosidenib (Tibsovo) as the first treatment of adult patients with relapsed/refractory acute myeloid leukemia (AML) and an isocitrate dehydrogenase-1 (IDH1) mutation.
More specifically, the oral treatment has been approved for patients whose mutations have been identified by the Abbott RealTime IDH1 assay, a companion diagnostic test.
The approval was based on results from a phase 1, open-label, single-arm, multicenter, dose-escalation and expansion trial of adult patients in this AML population. The primary end point was combined complete remission and complete remission with partial hematologic improvement; this combined rate was 32.8%, and the median duration of this remission was 8.2 months.
The most serious adverse events included differentiation syndrome, QTc prolongation, and Guillain-Barré syndrome. Other adverse reactions included fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, and constipation.
Ivosidenib is marketed as Tibsovo by Agios Pharmaceuticals. The RealTime IDH1 Assay is marketed by Abbott Laboratories.
The Food and Drug Administration has approved ivosidenib (Tibsovo) as the first treatment of adult patients with relapsed/refractory acute myeloid leukemia (AML) and an isocitrate dehydrogenase-1 (IDH1) mutation.
More specifically, the oral treatment has been approved for patients whose mutations have been identified by the Abbott RealTime IDH1 assay, a companion diagnostic test.
The approval was based on results from a phase 1, open-label, single-arm, multicenter, dose-escalation and expansion trial of adult patients in this AML population. The primary end point was combined complete remission and complete remission with partial hematologic improvement; this combined rate was 32.8%, and the median duration of this remission was 8.2 months.
The most serious adverse events included differentiation syndrome, QTc prolongation, and Guillain-Barré syndrome. Other adverse reactions included fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, and constipation.
Ivosidenib is marketed as Tibsovo by Agios Pharmaceuticals. The RealTime IDH1 Assay is marketed by Abbott Laboratories.
CREDENCE canagliflozin trial halted because of efficacy
The CREDENCE trial, which was investigating whether the antidiabetes drug canagliflozin (Invokana) plus standard of care could safely help prevent or slow chronic kidney disease (CKD) in patients with type 2 diabetes, has been ended early because it has already achieved prespecified efficacy criteria, Janssen announced in a press release. These criteria included risk reduction in the composite endpoint of time to dialysis or kidney transplant, doubling of serum creatinine, and renal or cardiovascular death.
In CANVAS, the cardiovascular outcomes trial for canagliflozin, treatment was linked to reductions in progression of albuminuria and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal replacement therapy, or death from renal causes, compared with placebo, but those didn’t reach statistical significance.
CREDENCE (Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial that enrolled roughly 4,400 patients with type 2 diabetes and established kidney disease who had been receiving ACE inhibitors or angiotensin II receptor blockers for at least 4 weeks prior to randomization.
The decision to halt CREDENCE came about after a review of data by the study’s independent data monitoring committee during a planned interim analysis. The resulting recommendation was based on the efficacy findings, the exact data for which have not yet been released.
Canagliflozin, a sodium-glucose transporter 2 (SGLT2) inhibitor, in conjunction with diet and exercise, can help improve glycemic control. In the context of kidney disease and type 2 diabetes, canagliflozin has been associated with increased risk of dehydration, vaginal or penile yeast infections, and amputations of all or part of the foot or leg. It has also been associated with ketoacidosis, kidney problems, hyperkalemia, hypoglycemia, and urinary tract infections.
More information can be found in the press release. Full prescribing information can be found on the Food and Drug Administration website.
The CREDENCE trial, which was investigating whether the antidiabetes drug canagliflozin (Invokana) plus standard of care could safely help prevent or slow chronic kidney disease (CKD) in patients with type 2 diabetes, has been ended early because it has already achieved prespecified efficacy criteria, Janssen announced in a press release. These criteria included risk reduction in the composite endpoint of time to dialysis or kidney transplant, doubling of serum creatinine, and renal or cardiovascular death.
In CANVAS, the cardiovascular outcomes trial for canagliflozin, treatment was linked to reductions in progression of albuminuria and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal replacement therapy, or death from renal causes, compared with placebo, but those didn’t reach statistical significance.
CREDENCE (Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial that enrolled roughly 4,400 patients with type 2 diabetes and established kidney disease who had been receiving ACE inhibitors or angiotensin II receptor blockers for at least 4 weeks prior to randomization.
The decision to halt CREDENCE came about after a review of data by the study’s independent data monitoring committee during a planned interim analysis. The resulting recommendation was based on the efficacy findings, the exact data for which have not yet been released.
Canagliflozin, a sodium-glucose transporter 2 (SGLT2) inhibitor, in conjunction with diet and exercise, can help improve glycemic control. In the context of kidney disease and type 2 diabetes, canagliflozin has been associated with increased risk of dehydration, vaginal or penile yeast infections, and amputations of all or part of the foot or leg. It has also been associated with ketoacidosis, kidney problems, hyperkalemia, hypoglycemia, and urinary tract infections.
More information can be found in the press release. Full prescribing information can be found on the Food and Drug Administration website.
The CREDENCE trial, which was investigating whether the antidiabetes drug canagliflozin (Invokana) plus standard of care could safely help prevent or slow chronic kidney disease (CKD) in patients with type 2 diabetes, has been ended early because it has already achieved prespecified efficacy criteria, Janssen announced in a press release. These criteria included risk reduction in the composite endpoint of time to dialysis or kidney transplant, doubling of serum creatinine, and renal or cardiovascular death.
In CANVAS, the cardiovascular outcomes trial for canagliflozin, treatment was linked to reductions in progression of albuminuria and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal replacement therapy, or death from renal causes, compared with placebo, but those didn’t reach statistical significance.
CREDENCE (Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial that enrolled roughly 4,400 patients with type 2 diabetes and established kidney disease who had been receiving ACE inhibitors or angiotensin II receptor blockers for at least 4 weeks prior to randomization.
The decision to halt CREDENCE came about after a review of data by the study’s independent data monitoring committee during a planned interim analysis. The resulting recommendation was based on the efficacy findings, the exact data for which have not yet been released.
Canagliflozin, a sodium-glucose transporter 2 (SGLT2) inhibitor, in conjunction with diet and exercise, can help improve glycemic control. In the context of kidney disease and type 2 diabetes, canagliflozin has been associated with increased risk of dehydration, vaginal or penile yeast infections, and amputations of all or part of the foot or leg. It has also been associated with ketoacidosis, kidney problems, hyperkalemia, hypoglycemia, and urinary tract infections.
More information can be found in the press release. Full prescribing information can be found on the Food and Drug Administration website.
FDA approves enzalutamide for non-metastatic CRPC
The Food and Drug Administration has expanded the prostate cancer indication for enzalutamide to include nonmetastatic castration-resistant prostate cancer (CRPC). The androgen-receptor inhibitor was first approved in 2012 for the treatment of patients with metastatic CRPC who had previously received chemotherapy and was granted approval in 2014 for men with metastatic CRPC who had not received chemotherapy.
The current approval was based on a statistically significant improvement in metastasis-free survival for patients receiving enzalutamide in the phase 3 PROSPER trial, a trial that randomized 1,401 patients (2:1) with nonmetastatic CRPC to 160 mg of oral enzalutamide daily or to placebo. Median metastasis-free survival was 36.6 months for those receiving enzalutamide versus 14.7 months for those receiving placebo (hazard ratio, 0.29; 95% confidence interval, 0.24-0.35; P less than .0001), the FDA said in a press statement.
The most common adverse events were asthenia/fatigue, hot flush, hypertension, dizziness, nausea, and falls.
The recommended dose for enzalutamide, marketed as Xtandi by Astellas Pharma US, is 160 mg (four 40-mg capsules) administered orally once daily.
The Food and Drug Administration has expanded the prostate cancer indication for enzalutamide to include nonmetastatic castration-resistant prostate cancer (CRPC). The androgen-receptor inhibitor was first approved in 2012 for the treatment of patients with metastatic CRPC who had previously received chemotherapy and was granted approval in 2014 for men with metastatic CRPC who had not received chemotherapy.
The current approval was based on a statistically significant improvement in metastasis-free survival for patients receiving enzalutamide in the phase 3 PROSPER trial, a trial that randomized 1,401 patients (2:1) with nonmetastatic CRPC to 160 mg of oral enzalutamide daily or to placebo. Median metastasis-free survival was 36.6 months for those receiving enzalutamide versus 14.7 months for those receiving placebo (hazard ratio, 0.29; 95% confidence interval, 0.24-0.35; P less than .0001), the FDA said in a press statement.
The most common adverse events were asthenia/fatigue, hot flush, hypertension, dizziness, nausea, and falls.
The recommended dose for enzalutamide, marketed as Xtandi by Astellas Pharma US, is 160 mg (four 40-mg capsules) administered orally once daily.
The Food and Drug Administration has expanded the prostate cancer indication for enzalutamide to include nonmetastatic castration-resistant prostate cancer (CRPC). The androgen-receptor inhibitor was first approved in 2012 for the treatment of patients with metastatic CRPC who had previously received chemotherapy and was granted approval in 2014 for men with metastatic CRPC who had not received chemotherapy.
The current approval was based on a statistically significant improvement in metastasis-free survival for patients receiving enzalutamide in the phase 3 PROSPER trial, a trial that randomized 1,401 patients (2:1) with nonmetastatic CRPC to 160 mg of oral enzalutamide daily or to placebo. Median metastasis-free survival was 36.6 months for those receiving enzalutamide versus 14.7 months for those receiving placebo (hazard ratio, 0.29; 95% confidence interval, 0.24-0.35; P less than .0001), the FDA said in a press statement.
The most common adverse events were asthenia/fatigue, hot flush, hypertension, dizziness, nausea, and falls.
The recommended dose for enzalutamide, marketed as Xtandi by Astellas Pharma US, is 160 mg (four 40-mg capsules) administered orally once daily.
AHRQ National Guideline Clearinghouse shutting down
The Agency for Healthcare Research and Quality has announced that after July 16, 2018, its National Guideline Clearinghouse (NGC) website (guideline.gov) will no longer be available because its federal funding will be discontinued. According to the NGC website, its mission is to provide “an accessible mechanism for obtaining objective, detailed information on clinical practice guidelines and to further their dissemination, implementation, and use.”
Its services, all free to use, included providing summaries of each guideline, side-by-side comparisons of two or more guidelines, and syntheses of guidelines covering similar topics, highlighting areas of similarity and difference.
Update, July 17, 2018: Now that the guidelines are no longer available on the government site, ECRI Institute, the independent nonprofit that developed and maintained the National Guidelines Clearinghouse since its inception 20 years ago, “announced plans to continue providing this critical service to the healthcare community.” The ECRI Institute stated that they will launch an interim website this Fall “with many additional features planned for the near future.” Participating guideline developers will be able to access and contribute to the website free of charge, according to the company, while others will be charged a fee. In addition, as a temporary stop-gap, Fred Trotter, founder and CTO of CareSet Systems, a Medicare data use site, voluntarily cloned the complete guidelines before the government site shut down and made them available for public use here: https://github.com/CareSet/AHRQ_search_clone.
The Agency for Healthcare Research and Quality has announced that after July 16, 2018, its National Guideline Clearinghouse (NGC) website (guideline.gov) will no longer be available because its federal funding will be discontinued. According to the NGC website, its mission is to provide “an accessible mechanism for obtaining objective, detailed information on clinical practice guidelines and to further their dissemination, implementation, and use.”
Its services, all free to use, included providing summaries of each guideline, side-by-side comparisons of two or more guidelines, and syntheses of guidelines covering similar topics, highlighting areas of similarity and difference.
Update, July 17, 2018: Now that the guidelines are no longer available on the government site, ECRI Institute, the independent nonprofit that developed and maintained the National Guidelines Clearinghouse since its inception 20 years ago, “announced plans to continue providing this critical service to the healthcare community.” The ECRI Institute stated that they will launch an interim website this Fall “with many additional features planned for the near future.” Participating guideline developers will be able to access and contribute to the website free of charge, according to the company, while others will be charged a fee. In addition, as a temporary stop-gap, Fred Trotter, founder and CTO of CareSet Systems, a Medicare data use site, voluntarily cloned the complete guidelines before the government site shut down and made them available for public use here: https://github.com/CareSet/AHRQ_search_clone.
The Agency for Healthcare Research and Quality has announced that after July 16, 2018, its National Guideline Clearinghouse (NGC) website (guideline.gov) will no longer be available because its federal funding will be discontinued. According to the NGC website, its mission is to provide “an accessible mechanism for obtaining objective, detailed information on clinical practice guidelines and to further their dissemination, implementation, and use.”
Its services, all free to use, included providing summaries of each guideline, side-by-side comparisons of two or more guidelines, and syntheses of guidelines covering similar topics, highlighting areas of similarity and difference.
Update, July 17, 2018: Now that the guidelines are no longer available on the government site, ECRI Institute, the independent nonprofit that developed and maintained the National Guidelines Clearinghouse since its inception 20 years ago, “announced plans to continue providing this critical service to the healthcare community.” The ECRI Institute stated that they will launch an interim website this Fall “with many additional features planned for the near future.” Participating guideline developers will be able to access and contribute to the website free of charge, according to the company, while others will be charged a fee. In addition, as a temporary stop-gap, Fred Trotter, founder and CTO of CareSet Systems, a Medicare data use site, voluntarily cloned the complete guidelines before the government site shut down and made them available for public use here: https://github.com/CareSet/AHRQ_search_clone.
FDA grants accelerated approval to ipilimumab/nivolumab combo for CRC
The Food and Drug Administration has granted accelerated approval to ipilimumab (Yervoy) for the treatment of colorectal cancer (CRC) in patients aged 12 years and older, in combination with nivolumab (Opdivo). Specifically, this indication is for microsatellite instability–high or mismatch repair deficient metastatic CRC that has progressed after treatment with a fluoropyrimidine, oxaliplatin, or irinotecan, the FDA said in a press announcement.
This new use has been added to the nivolumab labeling; nivolumab received an accelerated approval of its own on July 31, 2017, as a single-agent treatment for these kinds of CRCs.
These approvals were based on the overall response rate in the nonrandomized CheckMate 142 trial. In the multiple parallel-cohort, open-label study, 82 patients received 1 mg/kg of IV ipilimumab and 3 mg/kg of IV nivolumab every 3 weeks for four doses, followed by 3 mg/kg of IV nivolumab alone every 2 weeks until either radiographic progression or unacceptable toxicity.
Their overall response rate was 46%, and 89% of those responding had response durations greater than 6 months. These rates were higher than those observed in a separate cohort of 58 patients who received only nivolumab: 28% and 67%, respectively.
The most common adverse events were fatigue, diarrhea, pyrexia, musculoskeletal pain, abdominal pain, pruritus, nausea, rash, dyspnea, decreased appetite, and vomiting.
Full prescribing information for ipilimumab and nivolumab can be found on the FDA website.
The Food and Drug Administration has granted accelerated approval to ipilimumab (Yervoy) for the treatment of colorectal cancer (CRC) in patients aged 12 years and older, in combination with nivolumab (Opdivo). Specifically, this indication is for microsatellite instability–high or mismatch repair deficient metastatic CRC that has progressed after treatment with a fluoropyrimidine, oxaliplatin, or irinotecan, the FDA said in a press announcement.
This new use has been added to the nivolumab labeling; nivolumab received an accelerated approval of its own on July 31, 2017, as a single-agent treatment for these kinds of CRCs.
These approvals were based on the overall response rate in the nonrandomized CheckMate 142 trial. In the multiple parallel-cohort, open-label study, 82 patients received 1 mg/kg of IV ipilimumab and 3 mg/kg of IV nivolumab every 3 weeks for four doses, followed by 3 mg/kg of IV nivolumab alone every 2 weeks until either radiographic progression or unacceptable toxicity.
Their overall response rate was 46%, and 89% of those responding had response durations greater than 6 months. These rates were higher than those observed in a separate cohort of 58 patients who received only nivolumab: 28% and 67%, respectively.
The most common adverse events were fatigue, diarrhea, pyrexia, musculoskeletal pain, abdominal pain, pruritus, nausea, rash, dyspnea, decreased appetite, and vomiting.
Full prescribing information for ipilimumab and nivolumab can be found on the FDA website.
The Food and Drug Administration has granted accelerated approval to ipilimumab (Yervoy) for the treatment of colorectal cancer (CRC) in patients aged 12 years and older, in combination with nivolumab (Opdivo). Specifically, this indication is for microsatellite instability–high or mismatch repair deficient metastatic CRC that has progressed after treatment with a fluoropyrimidine, oxaliplatin, or irinotecan, the FDA said in a press announcement.
This new use has been added to the nivolumab labeling; nivolumab received an accelerated approval of its own on July 31, 2017, as a single-agent treatment for these kinds of CRCs.
These approvals were based on the overall response rate in the nonrandomized CheckMate 142 trial. In the multiple parallel-cohort, open-label study, 82 patients received 1 mg/kg of IV ipilimumab and 3 mg/kg of IV nivolumab every 3 weeks for four doses, followed by 3 mg/kg of IV nivolumab alone every 2 weeks until either radiographic progression or unacceptable toxicity.
Their overall response rate was 46%, and 89% of those responding had response durations greater than 6 months. These rates were higher than those observed in a separate cohort of 58 patients who received only nivolumab: 28% and 67%, respectively.
The most common adverse events were fatigue, diarrhea, pyrexia, musculoskeletal pain, abdominal pain, pruritus, nausea, rash, dyspnea, decreased appetite, and vomiting.
Full prescribing information for ipilimumab and nivolumab can be found on the FDA website.
Genentech submits sNDA for venetoclax in untreated AML
A supplemental new drug application (sNDA) for venetoclax (Venclexta) used in combination with either a hypomethylating agent or low-dose cytarabine (LDAC) for previously untreated acute myeloid leukemia has been submitted to the Food and Drug Administration by Genentech, which developed it.
Specifically, the sNDA is for these drug combinations in the treatment of AML patients ineligible for intensive chemotherapy, according to the announcement from Genentech.
The sNDA is based on results of two trials that included patients in this population. In the phase 1b M14-358 (NCT02203773), venetoclax was combined with either azacitidine or decitabine; patients treated with 400 mg of venetoclax had a complete remission rate of 73%, and the median overall survival across all doses of venetoclax was 17.5 months. Low white blood cell count with fever, low white blood cell count, anemia, low platelet count, and decreased potassium levels were the most common grade 3/4 adverse events (occurring in 10% or more of patients). In the phase 1b/2 study M14-387 (NCT02287233), venetoclax was used in combination with LDAC; patients treated with a 600-mg dose of venetoclax showed a complete response rate of 62%, and a median overall survival of 11.4 months. Low white blood cell count with fever, decreased potassium levels, pneumonia, disease progression, decreased phosphate levels, high blood pressure, and sepsis were the most common grade 3/4 adverse events seen in this study.
This sNDA follows FDA breakthrough therapy designations, based on these same trials, for these uses of venetoclax with either hypomethylating agents or LDAC. The FDA also recently approved venetoclax in combination with rituximab (Rituxan) for treatment of patients who have chronic lymphocytic leukemia or small lymphocytic lymphoma, with or without 17p depletion, and have been treated with at least one prior therapy.
“AML is an aggressive disease with the lowest survival rate of all leukemias, and we look forward to working closely with the FDA to bring this potential option to patients with this very difficult-to-treat blood cancer as soon as possible,” said Sandra Horning, MD, chief medical officer at Genentech.
More information is included in the full release.
A supplemental new drug application (sNDA) for venetoclax (Venclexta) used in combination with either a hypomethylating agent or low-dose cytarabine (LDAC) for previously untreated acute myeloid leukemia has been submitted to the Food and Drug Administration by Genentech, which developed it.
Specifically, the sNDA is for these drug combinations in the treatment of AML patients ineligible for intensive chemotherapy, according to the announcement from Genentech.
The sNDA is based on results of two trials that included patients in this population. In the phase 1b M14-358 (NCT02203773), venetoclax was combined with either azacitidine or decitabine; patients treated with 400 mg of venetoclax had a complete remission rate of 73%, and the median overall survival across all doses of venetoclax was 17.5 months. Low white blood cell count with fever, low white blood cell count, anemia, low platelet count, and decreased potassium levels were the most common grade 3/4 adverse events (occurring in 10% or more of patients). In the phase 1b/2 study M14-387 (NCT02287233), venetoclax was used in combination with LDAC; patients treated with a 600-mg dose of venetoclax showed a complete response rate of 62%, and a median overall survival of 11.4 months. Low white blood cell count with fever, decreased potassium levels, pneumonia, disease progression, decreased phosphate levels, high blood pressure, and sepsis were the most common grade 3/4 adverse events seen in this study.
This sNDA follows FDA breakthrough therapy designations, based on these same trials, for these uses of venetoclax with either hypomethylating agents or LDAC. The FDA also recently approved venetoclax in combination with rituximab (Rituxan) for treatment of patients who have chronic lymphocytic leukemia or small lymphocytic lymphoma, with or without 17p depletion, and have been treated with at least one prior therapy.
“AML is an aggressive disease with the lowest survival rate of all leukemias, and we look forward to working closely with the FDA to bring this potential option to patients with this very difficult-to-treat blood cancer as soon as possible,” said Sandra Horning, MD, chief medical officer at Genentech.
More information is included in the full release.
A supplemental new drug application (sNDA) for venetoclax (Venclexta) used in combination with either a hypomethylating agent or low-dose cytarabine (LDAC) for previously untreated acute myeloid leukemia has been submitted to the Food and Drug Administration by Genentech, which developed it.
Specifically, the sNDA is for these drug combinations in the treatment of AML patients ineligible for intensive chemotherapy, according to the announcement from Genentech.
The sNDA is based on results of two trials that included patients in this population. In the phase 1b M14-358 (NCT02203773), venetoclax was combined with either azacitidine or decitabine; patients treated with 400 mg of venetoclax had a complete remission rate of 73%, and the median overall survival across all doses of venetoclax was 17.5 months. Low white blood cell count with fever, low white blood cell count, anemia, low platelet count, and decreased potassium levels were the most common grade 3/4 adverse events (occurring in 10% or more of patients). In the phase 1b/2 study M14-387 (NCT02287233), venetoclax was used in combination with LDAC; patients treated with a 600-mg dose of venetoclax showed a complete response rate of 62%, and a median overall survival of 11.4 months. Low white blood cell count with fever, decreased potassium levels, pneumonia, disease progression, decreased phosphate levels, high blood pressure, and sepsis were the most common grade 3/4 adverse events seen in this study.
This sNDA follows FDA breakthrough therapy designations, based on these same trials, for these uses of venetoclax with either hypomethylating agents or LDAC. The FDA also recently approved venetoclax in combination with rituximab (Rituxan) for treatment of patients who have chronic lymphocytic leukemia or small lymphocytic lymphoma, with or without 17p depletion, and have been treated with at least one prior therapy.
“AML is an aggressive disease with the lowest survival rate of all leukemias, and we look forward to working closely with the FDA to bring this potential option to patients with this very difficult-to-treat blood cancer as soon as possible,” said Sandra Horning, MD, chief medical officer at Genentech.
More information is included in the full release.