User login
FDA OKs talquetamab, a first-in-class myeloma tx
Patients must have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
The agent, which also received breakthrough and orphan drug designation, is available only through the Tecvayli-Talvey Risk Evaluation and Mitigation Strategy (REMS) because of a boxed warning for life-threatening or fatal cytokine release syndrome (CRS) and neurological toxicity, including immune effector cell–associated neurotoxicity (ICANS), the FDA announced.
Talquetamab-tgvs was evaluated in the single-arm, open-label MonumenTAL-1 study of 187 patients who had previously been treated with at least four prior systemic therapies.
The overall response rate in 100 patients who received a subcutaneous dose of 0.4 mg/kg weekly was 73% and median duration of response was 9.5 months. The overall response rate in 87 patients who received a subcutaneous dose of 0.8 mg/kg biweekly was 73.6%, with about 85% of responders maintaining their response for at least 9 months. In this group, the median duration of response was not estimable.
Patients in the 0.4 mg/kg weekly dose group were treated following two step-up doses in the first week of therapy, and those in the 0.8 mg/kg biweekly group were treated following three step-up doses, until disease progression or unacceptable toxicity.
Adverse reactions occurring in at least 20% of the 339 patients in the safety population included CRS, dysgeusia (foul, metallic taste sensation), nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, decreased weight, dry mouth, pyrexia, xerosis, dysphagia, upper respiratory tract infection, and diarrhea.
Both the weekly 0.4 mg/kg and biweekly 0.8 mg/kg doses are recommended. The full dosing schedule is included in the prescribing information.
The approval follows a series of market withdrawals for other multiple myeloma drugs that initially received accelerated FDA approval. For instance, the FDA recently requested withdrawal of melphalan flufenamide (Pepaxto) after 2021 confirmatory trial results showed an increased risk of death. This agent had received accelerated approval in 2021. GlaxoSmithKline’s blood cancer drugs panobinostat (Farydak) and belantamab mafodotin-blmf (Blenrep) were also withdrawn based on confirmatory trial results.
Continued approval of talquetemab-tgvs for this indication is also contingent on verifying efficacy in confirmatory trials.
The new treatment approach represents a “welcome addition to the myeloma community,” Michael Andreini, president and chief executive officer of the Multiple Myeloma Research Foundation stated in a Janssen press release. “Although options for the treatment of multiple myeloma have expanded significantly in recent years, the disease remains incurable, and therefore, patients are in need of new treatment options.”
Health care professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
A version of this article first appeared on Medscape.com.
Patients must have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
The agent, which also received breakthrough and orphan drug designation, is available only through the Tecvayli-Talvey Risk Evaluation and Mitigation Strategy (REMS) because of a boxed warning for life-threatening or fatal cytokine release syndrome (CRS) and neurological toxicity, including immune effector cell–associated neurotoxicity (ICANS), the FDA announced.
Talquetamab-tgvs was evaluated in the single-arm, open-label MonumenTAL-1 study of 187 patients who had previously been treated with at least four prior systemic therapies.
The overall response rate in 100 patients who received a subcutaneous dose of 0.4 mg/kg weekly was 73% and median duration of response was 9.5 months. The overall response rate in 87 patients who received a subcutaneous dose of 0.8 mg/kg biweekly was 73.6%, with about 85% of responders maintaining their response for at least 9 months. In this group, the median duration of response was not estimable.
Patients in the 0.4 mg/kg weekly dose group were treated following two step-up doses in the first week of therapy, and those in the 0.8 mg/kg biweekly group were treated following three step-up doses, until disease progression or unacceptable toxicity.
Adverse reactions occurring in at least 20% of the 339 patients in the safety population included CRS, dysgeusia (foul, metallic taste sensation), nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, decreased weight, dry mouth, pyrexia, xerosis, dysphagia, upper respiratory tract infection, and diarrhea.
Both the weekly 0.4 mg/kg and biweekly 0.8 mg/kg doses are recommended. The full dosing schedule is included in the prescribing information.
The approval follows a series of market withdrawals for other multiple myeloma drugs that initially received accelerated FDA approval. For instance, the FDA recently requested withdrawal of melphalan flufenamide (Pepaxto) after 2021 confirmatory trial results showed an increased risk of death. This agent had received accelerated approval in 2021. GlaxoSmithKline’s blood cancer drugs panobinostat (Farydak) and belantamab mafodotin-blmf (Blenrep) were also withdrawn based on confirmatory trial results.
Continued approval of talquetemab-tgvs for this indication is also contingent on verifying efficacy in confirmatory trials.
The new treatment approach represents a “welcome addition to the myeloma community,” Michael Andreini, president and chief executive officer of the Multiple Myeloma Research Foundation stated in a Janssen press release. “Although options for the treatment of multiple myeloma have expanded significantly in recent years, the disease remains incurable, and therefore, patients are in need of new treatment options.”
Health care professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
A version of this article first appeared on Medscape.com.
Patients must have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
The agent, which also received breakthrough and orphan drug designation, is available only through the Tecvayli-Talvey Risk Evaluation and Mitigation Strategy (REMS) because of a boxed warning for life-threatening or fatal cytokine release syndrome (CRS) and neurological toxicity, including immune effector cell–associated neurotoxicity (ICANS), the FDA announced.
Talquetamab-tgvs was evaluated in the single-arm, open-label MonumenTAL-1 study of 187 patients who had previously been treated with at least four prior systemic therapies.
The overall response rate in 100 patients who received a subcutaneous dose of 0.4 mg/kg weekly was 73% and median duration of response was 9.5 months. The overall response rate in 87 patients who received a subcutaneous dose of 0.8 mg/kg biweekly was 73.6%, with about 85% of responders maintaining their response for at least 9 months. In this group, the median duration of response was not estimable.
Patients in the 0.4 mg/kg weekly dose group were treated following two step-up doses in the first week of therapy, and those in the 0.8 mg/kg biweekly group were treated following three step-up doses, until disease progression or unacceptable toxicity.
Adverse reactions occurring in at least 20% of the 339 patients in the safety population included CRS, dysgeusia (foul, metallic taste sensation), nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, decreased weight, dry mouth, pyrexia, xerosis, dysphagia, upper respiratory tract infection, and diarrhea.
Both the weekly 0.4 mg/kg and biweekly 0.8 mg/kg doses are recommended. The full dosing schedule is included in the prescribing information.
The approval follows a series of market withdrawals for other multiple myeloma drugs that initially received accelerated FDA approval. For instance, the FDA recently requested withdrawal of melphalan flufenamide (Pepaxto) after 2021 confirmatory trial results showed an increased risk of death. This agent had received accelerated approval in 2021. GlaxoSmithKline’s blood cancer drugs panobinostat (Farydak) and belantamab mafodotin-blmf (Blenrep) were also withdrawn based on confirmatory trial results.
Continued approval of talquetemab-tgvs for this indication is also contingent on verifying efficacy in confirmatory trials.
The new treatment approach represents a “welcome addition to the myeloma community,” Michael Andreini, president and chief executive officer of the Multiple Myeloma Research Foundation stated in a Janssen press release. “Although options for the treatment of multiple myeloma have expanded significantly in recent years, the disease remains incurable, and therefore, patients are in need of new treatment options.”
Health care professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
A version of this article first appeared on Medscape.com.
FDA OKs dostarlimab plus chemo for endometrial cancer
The U.S. Food and Drug Administration has approved dostarlimab-gxly (Jemperli, GlaxoSmithKline) with carboplatin and paclitaxel, followed by single-agent dostarlimab, for primary advanced or recurrent endometrial cancer that is mismatch repair–deficient (dMMR), as determined by an FDA-approved test or microsatellite instability–high (MSI-H).
The approval was based on GSK’s RUBY trial. Across 122 patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer, progression-free survival was 30.3 months in women randomly assigned to dostarlimab on a background of carboplatin and paclitaxel, followed by dostarlimab monotherapy, vs. 7.7 months among women randomly assigned to placebo (hazard ratio, 0.29; P < .0001), according to the FDA’s press release.
MMR/MSI tumor status was determined by local testing or by the Ventana MMR RxDx Panel when local testing was unavailable.
“Until now, chemotherapy alone has been the standard of care with many patients experiencing disease progression,” GSK executive Hesham Abdullah said in the company’s press release. The trial results “and today’s approval underscore our belief in the potential for Jemperli to transform cancer treatment as a backbone immuno-oncology therapy.”
that has progressed on or following a platinum-containing chemotherapy and is not a candidate for curative surgery or radiation. The latest approval means that the agent “is now indicated earlier in treatment in combination with chemotherapy,” GSK said.
Dostarlimab also carries an indication for dMMR recurrent or advanced solid tumors that have progressed on or following prior treatment when there are no satisfactory alternative treatment options.
Immune-mediated adverse reactions with dostarlimab include pneumonitis, colitis, hepatitis, endocrinopathies such as hypothyroidism, nephritis with renal dysfunction, and skin adverse reactions. The most common adverse reactions (≥ 20%) with carboplatin and paclitaxel in the Ruby trial were rash, diarrhea, hypothyroidism, and hypertension.
The recommended dostarlimab dose is 500 mg every 3 weeks for 6 doses with carboplatin and paclitaxel, followed by 1,000 mg monotherapy every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years.
Drugs.com lists dostarlimab’s price at $11,712.66 for 500 mg/10 mL intravenous solution.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has approved dostarlimab-gxly (Jemperli, GlaxoSmithKline) with carboplatin and paclitaxel, followed by single-agent dostarlimab, for primary advanced or recurrent endometrial cancer that is mismatch repair–deficient (dMMR), as determined by an FDA-approved test or microsatellite instability–high (MSI-H).
The approval was based on GSK’s RUBY trial. Across 122 patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer, progression-free survival was 30.3 months in women randomly assigned to dostarlimab on a background of carboplatin and paclitaxel, followed by dostarlimab monotherapy, vs. 7.7 months among women randomly assigned to placebo (hazard ratio, 0.29; P < .0001), according to the FDA’s press release.
MMR/MSI tumor status was determined by local testing or by the Ventana MMR RxDx Panel when local testing was unavailable.
“Until now, chemotherapy alone has been the standard of care with many patients experiencing disease progression,” GSK executive Hesham Abdullah said in the company’s press release. The trial results “and today’s approval underscore our belief in the potential for Jemperli to transform cancer treatment as a backbone immuno-oncology therapy.”
that has progressed on or following a platinum-containing chemotherapy and is not a candidate for curative surgery or radiation. The latest approval means that the agent “is now indicated earlier in treatment in combination with chemotherapy,” GSK said.
Dostarlimab also carries an indication for dMMR recurrent or advanced solid tumors that have progressed on or following prior treatment when there are no satisfactory alternative treatment options.
Immune-mediated adverse reactions with dostarlimab include pneumonitis, colitis, hepatitis, endocrinopathies such as hypothyroidism, nephritis with renal dysfunction, and skin adverse reactions. The most common adverse reactions (≥ 20%) with carboplatin and paclitaxel in the Ruby trial were rash, diarrhea, hypothyroidism, and hypertension.
The recommended dostarlimab dose is 500 mg every 3 weeks for 6 doses with carboplatin and paclitaxel, followed by 1,000 mg monotherapy every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years.
Drugs.com lists dostarlimab’s price at $11,712.66 for 500 mg/10 mL intravenous solution.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has approved dostarlimab-gxly (Jemperli, GlaxoSmithKline) with carboplatin and paclitaxel, followed by single-agent dostarlimab, for primary advanced or recurrent endometrial cancer that is mismatch repair–deficient (dMMR), as determined by an FDA-approved test or microsatellite instability–high (MSI-H).
The approval was based on GSK’s RUBY trial. Across 122 patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer, progression-free survival was 30.3 months in women randomly assigned to dostarlimab on a background of carboplatin and paclitaxel, followed by dostarlimab monotherapy, vs. 7.7 months among women randomly assigned to placebo (hazard ratio, 0.29; P < .0001), according to the FDA’s press release.
MMR/MSI tumor status was determined by local testing or by the Ventana MMR RxDx Panel when local testing was unavailable.
“Until now, chemotherapy alone has been the standard of care with many patients experiencing disease progression,” GSK executive Hesham Abdullah said in the company’s press release. The trial results “and today’s approval underscore our belief in the potential for Jemperli to transform cancer treatment as a backbone immuno-oncology therapy.”
that has progressed on or following a platinum-containing chemotherapy and is not a candidate for curative surgery or radiation. The latest approval means that the agent “is now indicated earlier in treatment in combination with chemotherapy,” GSK said.
Dostarlimab also carries an indication for dMMR recurrent or advanced solid tumors that have progressed on or following prior treatment when there are no satisfactory alternative treatment options.
Immune-mediated adverse reactions with dostarlimab include pneumonitis, colitis, hepatitis, endocrinopathies such as hypothyroidism, nephritis with renal dysfunction, and skin adverse reactions. The most common adverse reactions (≥ 20%) with carboplatin and paclitaxel in the Ruby trial were rash, diarrhea, hypothyroidism, and hypertension.
The recommended dostarlimab dose is 500 mg every 3 weeks for 6 doses with carboplatin and paclitaxel, followed by 1,000 mg monotherapy every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years.
Drugs.com lists dostarlimab’s price at $11,712.66 for 500 mg/10 mL intravenous solution.
A version of this article first appeared on Medscape.com.
FDA approves cantharidin for molluscum contagiosum
On July 21, 2023, .
The product is a drug-device combination that contains a formulation of cantharidin solution (0.7%), delivered topically via a single-use applicator, which allows for precise dosing and targeted administration. According to a press release from Verrica Pharmaceuticals, cantharidin is expected to be available by September 2023 and should be administered only by a trained health care professional; it is not for use in the home.
The approval of the product, also known as VP-102, is based on results from two identical multicenter phase 3 randomized, double-blind, placebo-controlled trials that evaluated the drug’s safety and efficacy in patients 2 years of age and older diagnosed with molluscum: Cantharidin Application in Molluscum Patients-1 (CAMP-1) and CAMP-2. Patients in both trials met the primary endpoint of complete clearance of all treatable molluscum lesions. Specifically, 46% of CAMP-1 participants treated with VP-102 achieved complete clearance of molluscum lesions compared with 18% of participants in the vehicle group (P < .0001), while 54% of CAMP-2 participants treated with VP-102 achieved complete clearance of molluscum lesions compared with 13% of participants in the vehicle group (P < .0001).
A post hoc analysis of both trials found that complete clearance of all lesions was significantly higher in the VP-102 group than vehicle across all body regions. It also found that there were no serious adverse reactions reported in the trials. Adverse reactions were mostly mild to moderate and included application site vesicles, erythema, pain, dryness, scab, discoloration, pruritus, and edema.
The product will be marketed as Ycanth.
In March of 2023, the FDA accepted a new drug application for another treatment for molluscum contagiosum, berdazimer gel 10.3%. That product is being developed by Novan.
On July 21, 2023, .
The product is a drug-device combination that contains a formulation of cantharidin solution (0.7%), delivered topically via a single-use applicator, which allows for precise dosing and targeted administration. According to a press release from Verrica Pharmaceuticals, cantharidin is expected to be available by September 2023 and should be administered only by a trained health care professional; it is not for use in the home.
The approval of the product, also known as VP-102, is based on results from two identical multicenter phase 3 randomized, double-blind, placebo-controlled trials that evaluated the drug’s safety and efficacy in patients 2 years of age and older diagnosed with molluscum: Cantharidin Application in Molluscum Patients-1 (CAMP-1) and CAMP-2. Patients in both trials met the primary endpoint of complete clearance of all treatable molluscum lesions. Specifically, 46% of CAMP-1 participants treated with VP-102 achieved complete clearance of molluscum lesions compared with 18% of participants in the vehicle group (P < .0001), while 54% of CAMP-2 participants treated with VP-102 achieved complete clearance of molluscum lesions compared with 13% of participants in the vehicle group (P < .0001).
A post hoc analysis of both trials found that complete clearance of all lesions was significantly higher in the VP-102 group than vehicle across all body regions. It also found that there were no serious adverse reactions reported in the trials. Adverse reactions were mostly mild to moderate and included application site vesicles, erythema, pain, dryness, scab, discoloration, pruritus, and edema.
The product will be marketed as Ycanth.
In March of 2023, the FDA accepted a new drug application for another treatment for molluscum contagiosum, berdazimer gel 10.3%. That product is being developed by Novan.
On July 21, 2023, .
The product is a drug-device combination that contains a formulation of cantharidin solution (0.7%), delivered topically via a single-use applicator, which allows for precise dosing and targeted administration. According to a press release from Verrica Pharmaceuticals, cantharidin is expected to be available by September 2023 and should be administered only by a trained health care professional; it is not for use in the home.
The approval of the product, also known as VP-102, is based on results from two identical multicenter phase 3 randomized, double-blind, placebo-controlled trials that evaluated the drug’s safety and efficacy in patients 2 years of age and older diagnosed with molluscum: Cantharidin Application in Molluscum Patients-1 (CAMP-1) and CAMP-2. Patients in both trials met the primary endpoint of complete clearance of all treatable molluscum lesions. Specifically, 46% of CAMP-1 participants treated with VP-102 achieved complete clearance of molluscum lesions compared with 18% of participants in the vehicle group (P < .0001), while 54% of CAMP-2 participants treated with VP-102 achieved complete clearance of molluscum lesions compared with 13% of participants in the vehicle group (P < .0001).
A post hoc analysis of both trials found that complete clearance of all lesions was significantly higher in the VP-102 group than vehicle across all body regions. It also found that there were no serious adverse reactions reported in the trials. Adverse reactions were mostly mild to moderate and included application site vesicles, erythema, pain, dryness, scab, discoloration, pruritus, and edema.
The product will be marketed as Ycanth.
In March of 2023, the FDA accepted a new drug application for another treatment for molluscum contagiosum, berdazimer gel 10.3%. That product is being developed by Novan.
FDA approves quizartinib for newly diagnosed AML
On July 20 the FDA also approved the LeukoStrat CDx FLT3 Mutation Assay to determine whether patients have this mutation.
The agency granted quizartinib a first-line indication for use in combination with standard chemotherapy – cytarabine and anthracycline induction followed by cytarabine consolidation – and as maintenance monotherapy afterwards, in adults whose tumors express FLT3-ITD.
The FLT3 protein is a tyrosine kinase receptor found on hematopoietic stem cells. Wild-type FLT3 promotes cell survival, growth, and differentiation, but ITD (internal tandem duplication)-mutated FLT3, which quizartinib targets, is associated with a higher relapse risk and shorter survival. About a quarter of AML patients carry the mutation.
Approval was based on the phase 3 QuANTUM-First trial in over 500 patients with the mutation. Median overall survival among patients on standard chemotherapy randomly assigned to quizartinib was 31.9 months versus 15.1 months in patients randomly assigned to placebo, a 22.4% reduction in the risk of death (P = .0324).
Quizartinib is not indicated as maintenance monotherapy after allogeneic hematopoietic stem cell transplantation.
In a company press release, the drug’s manufacturer Daiichi Sankyo said quizartinib will be available in the United States soon.
Company executive Ken Takeshita, MD, called the approval “an important milestone, as patients with the FLT3-ITD subtype of AML can now be treated with the first-ever FLT3 inhibitor approved across the three phases of treatment these patients typically receive.”
The FDA’s original decision date was April 24, but the agency pushed it back 3 months to review updates Daiichi Sankyo made to quizartinib’s Risk Evaluation and Mitigation Strategies (REMS) program in response to an agency request.
Quizartinib carries a boxed warning of QT prolongation, torsades de pointes, and cardiac arrest. Because of these risks, it’s only available through a new program, dubbed “Vanflyta REMS.”
In the trial, the most common adverse with quizartinib included lymphopenia (60%), hypokalemia (59%), hypoalbuminemia (53%), hypophosphatemia (52%), alkaline phosphatase increased (51%), hypomagnesemia (44%), febrile neutropenia (44%), diarrhea (42%), mucositis (38%), nausea (34%), and hypocalcemia (33%), among others.
The most common grade 3/4 adverse events were febrile neutropenia (43% with quizartinib vs. 41% with placebo), neutropenia (18% vs. 9%), hypokalemia (19% vs. 16%), and pneumonia (11% both). Adverse events were fatal in 11.3% of patients receiving quizartinib versus 9.7% of patients on placebo, mostly caused by infections.
In 2019, the FDA rejected quizartinib for FLT3-ITD mutated relapsed/refractory AML monotherapy in adults, after most of its oncology advisers thought the risk of treatment outweighed the benefits in an earlier trial.
A version of this article first appeared on Medscape.com.
On July 20 the FDA also approved the LeukoStrat CDx FLT3 Mutation Assay to determine whether patients have this mutation.
The agency granted quizartinib a first-line indication for use in combination with standard chemotherapy – cytarabine and anthracycline induction followed by cytarabine consolidation – and as maintenance monotherapy afterwards, in adults whose tumors express FLT3-ITD.
The FLT3 protein is a tyrosine kinase receptor found on hematopoietic stem cells. Wild-type FLT3 promotes cell survival, growth, and differentiation, but ITD (internal tandem duplication)-mutated FLT3, which quizartinib targets, is associated with a higher relapse risk and shorter survival. About a quarter of AML patients carry the mutation.
Approval was based on the phase 3 QuANTUM-First trial in over 500 patients with the mutation. Median overall survival among patients on standard chemotherapy randomly assigned to quizartinib was 31.9 months versus 15.1 months in patients randomly assigned to placebo, a 22.4% reduction in the risk of death (P = .0324).
Quizartinib is not indicated as maintenance monotherapy after allogeneic hematopoietic stem cell transplantation.
In a company press release, the drug’s manufacturer Daiichi Sankyo said quizartinib will be available in the United States soon.
Company executive Ken Takeshita, MD, called the approval “an important milestone, as patients with the FLT3-ITD subtype of AML can now be treated with the first-ever FLT3 inhibitor approved across the three phases of treatment these patients typically receive.”
The FDA’s original decision date was April 24, but the agency pushed it back 3 months to review updates Daiichi Sankyo made to quizartinib’s Risk Evaluation and Mitigation Strategies (REMS) program in response to an agency request.
Quizartinib carries a boxed warning of QT prolongation, torsades de pointes, and cardiac arrest. Because of these risks, it’s only available through a new program, dubbed “Vanflyta REMS.”
In the trial, the most common adverse with quizartinib included lymphopenia (60%), hypokalemia (59%), hypoalbuminemia (53%), hypophosphatemia (52%), alkaline phosphatase increased (51%), hypomagnesemia (44%), febrile neutropenia (44%), diarrhea (42%), mucositis (38%), nausea (34%), and hypocalcemia (33%), among others.
The most common grade 3/4 adverse events were febrile neutropenia (43% with quizartinib vs. 41% with placebo), neutropenia (18% vs. 9%), hypokalemia (19% vs. 16%), and pneumonia (11% both). Adverse events were fatal in 11.3% of patients receiving quizartinib versus 9.7% of patients on placebo, mostly caused by infections.
In 2019, the FDA rejected quizartinib for FLT3-ITD mutated relapsed/refractory AML monotherapy in adults, after most of its oncology advisers thought the risk of treatment outweighed the benefits in an earlier trial.
A version of this article first appeared on Medscape.com.
On July 20 the FDA also approved the LeukoStrat CDx FLT3 Mutation Assay to determine whether patients have this mutation.
The agency granted quizartinib a first-line indication for use in combination with standard chemotherapy – cytarabine and anthracycline induction followed by cytarabine consolidation – and as maintenance monotherapy afterwards, in adults whose tumors express FLT3-ITD.
The FLT3 protein is a tyrosine kinase receptor found on hematopoietic stem cells. Wild-type FLT3 promotes cell survival, growth, and differentiation, but ITD (internal tandem duplication)-mutated FLT3, which quizartinib targets, is associated with a higher relapse risk and shorter survival. About a quarter of AML patients carry the mutation.
Approval was based on the phase 3 QuANTUM-First trial in over 500 patients with the mutation. Median overall survival among patients on standard chemotherapy randomly assigned to quizartinib was 31.9 months versus 15.1 months in patients randomly assigned to placebo, a 22.4% reduction in the risk of death (P = .0324).
Quizartinib is not indicated as maintenance monotherapy after allogeneic hematopoietic stem cell transplantation.
In a company press release, the drug’s manufacturer Daiichi Sankyo said quizartinib will be available in the United States soon.
Company executive Ken Takeshita, MD, called the approval “an important milestone, as patients with the FLT3-ITD subtype of AML can now be treated with the first-ever FLT3 inhibitor approved across the three phases of treatment these patients typically receive.”
The FDA’s original decision date was April 24, but the agency pushed it back 3 months to review updates Daiichi Sankyo made to quizartinib’s Risk Evaluation and Mitigation Strategies (REMS) program in response to an agency request.
Quizartinib carries a boxed warning of QT prolongation, torsades de pointes, and cardiac arrest. Because of these risks, it’s only available through a new program, dubbed “Vanflyta REMS.”
In the trial, the most common adverse with quizartinib included lymphopenia (60%), hypokalemia (59%), hypoalbuminemia (53%), hypophosphatemia (52%), alkaline phosphatase increased (51%), hypomagnesemia (44%), febrile neutropenia (44%), diarrhea (42%), mucositis (38%), nausea (34%), and hypocalcemia (33%), among others.
The most common grade 3/4 adverse events were febrile neutropenia (43% with quizartinib vs. 41% with placebo), neutropenia (18% vs. 9%), hypokalemia (19% vs. 16%), and pneumonia (11% both). Adverse events were fatal in 11.3% of patients receiving quizartinib versus 9.7% of patients on placebo, mostly caused by infections.
In 2019, the FDA rejected quizartinib for FLT3-ITD mutated relapsed/refractory AML monotherapy in adults, after most of its oncology advisers thought the risk of treatment outweighed the benefits in an earlier trial.
A version of this article first appeared on Medscape.com.
More children missing developmental milestones: Survey
Nearly 9 out of every 100 U.S. children are now diagnosed with a developmental disability, according to updated figures from the CDC.
Developmental disabilities include autism, intellectual disabilities such as Down syndrome, and a range of other diagnoses related to missing developmental milestones in how a child plays, learns, or speaks.
The newly reported increase amounts to just over 1 percentage point from 2019 to 2021. In 2019, the rate of developmental disability diagnoses was about 7 in 100 children. The latest figures are from 2021 data, published this week after the CDC finished analyzing responses to the National Health Survey.
Among children ages 3-17 years old in 2021, the survey showed that:
- 1.7% had an intellectual disability.
- 3.1% had autism spectrum disorder.
- 6.1% had a diagnosis of “other developmental delay.”
No significant change was seen from 2019 to 2021 in how common it was for survey respondents to report children having autism or an intellectual disability. The overall increase was driven by a jump in reports from parents that a doctor or health professional told them their child had “any other developmental delay,” excluding autism spectrum disorder or an intellectual disability.
“A lot of times developmental delays might be temporary diagnoses that evolve into something like autism, potentially, or intellectual disability. But also a lot of times children do age out of those,” lead report author and CDC statistician Benjamin Zablotsky, PhD, told CBS News.
The CDC offers an app called Milestone Tracker to help parents watch for signs of developmental delays, in addition to operating a public health education program called “Learn the Signs. Act Early.”
The new report showed that boys were nearly twice as likely as girls to have any developmental delay, a pattern that was magnified when looking specifically at autism diagnoses. Boys were more than three times as likely as girls to be diagnosed with autism spectrum disorder. The rate of autism among boys was 4.7%, compared with 1.5% among girls.
While these latest survey results showed consistent rates of autism from 2019 to 2021, a different CDC report earlier this year showed an alarming jump in the rate of autism spectrum disorder among 8-year-olds. That report, which compared data from 2008 to 2020, showed the rate of autism among 8-year-olds rose during those 12 years from 1 in 88 kids to 1 in 36 kids.
The two analyses also differed in their findings regarding prevalence of autism when looking at children by race and ethnicity. The report from earlier this year showed that Black and Hispanic children were more likely to be diagnosed with autism, compared with White children. This latest report did not find any differences in the prevalence of autism based on a child’s race or ethnicity.
A version of this article appeared on WebMD.com.
Nearly 9 out of every 100 U.S. children are now diagnosed with a developmental disability, according to updated figures from the CDC.
Developmental disabilities include autism, intellectual disabilities such as Down syndrome, and a range of other diagnoses related to missing developmental milestones in how a child plays, learns, or speaks.
The newly reported increase amounts to just over 1 percentage point from 2019 to 2021. In 2019, the rate of developmental disability diagnoses was about 7 in 100 children. The latest figures are from 2021 data, published this week after the CDC finished analyzing responses to the National Health Survey.
Among children ages 3-17 years old in 2021, the survey showed that:
- 1.7% had an intellectual disability.
- 3.1% had autism spectrum disorder.
- 6.1% had a diagnosis of “other developmental delay.”
No significant change was seen from 2019 to 2021 in how common it was for survey respondents to report children having autism or an intellectual disability. The overall increase was driven by a jump in reports from parents that a doctor or health professional told them their child had “any other developmental delay,” excluding autism spectrum disorder or an intellectual disability.
“A lot of times developmental delays might be temporary diagnoses that evolve into something like autism, potentially, or intellectual disability. But also a lot of times children do age out of those,” lead report author and CDC statistician Benjamin Zablotsky, PhD, told CBS News.
The CDC offers an app called Milestone Tracker to help parents watch for signs of developmental delays, in addition to operating a public health education program called “Learn the Signs. Act Early.”
The new report showed that boys were nearly twice as likely as girls to have any developmental delay, a pattern that was magnified when looking specifically at autism diagnoses. Boys were more than three times as likely as girls to be diagnosed with autism spectrum disorder. The rate of autism among boys was 4.7%, compared with 1.5% among girls.
While these latest survey results showed consistent rates of autism from 2019 to 2021, a different CDC report earlier this year showed an alarming jump in the rate of autism spectrum disorder among 8-year-olds. That report, which compared data from 2008 to 2020, showed the rate of autism among 8-year-olds rose during those 12 years from 1 in 88 kids to 1 in 36 kids.
The two analyses also differed in their findings regarding prevalence of autism when looking at children by race and ethnicity. The report from earlier this year showed that Black and Hispanic children were more likely to be diagnosed with autism, compared with White children. This latest report did not find any differences in the prevalence of autism based on a child’s race or ethnicity.
A version of this article appeared on WebMD.com.
Nearly 9 out of every 100 U.S. children are now diagnosed with a developmental disability, according to updated figures from the CDC.
Developmental disabilities include autism, intellectual disabilities such as Down syndrome, and a range of other diagnoses related to missing developmental milestones in how a child plays, learns, or speaks.
The newly reported increase amounts to just over 1 percentage point from 2019 to 2021. In 2019, the rate of developmental disability diagnoses was about 7 in 100 children. The latest figures are from 2021 data, published this week after the CDC finished analyzing responses to the National Health Survey.
Among children ages 3-17 years old in 2021, the survey showed that:
- 1.7% had an intellectual disability.
- 3.1% had autism spectrum disorder.
- 6.1% had a diagnosis of “other developmental delay.”
No significant change was seen from 2019 to 2021 in how common it was for survey respondents to report children having autism or an intellectual disability. The overall increase was driven by a jump in reports from parents that a doctor or health professional told them their child had “any other developmental delay,” excluding autism spectrum disorder or an intellectual disability.
“A lot of times developmental delays might be temporary diagnoses that evolve into something like autism, potentially, or intellectual disability. But also a lot of times children do age out of those,” lead report author and CDC statistician Benjamin Zablotsky, PhD, told CBS News.
The CDC offers an app called Milestone Tracker to help parents watch for signs of developmental delays, in addition to operating a public health education program called “Learn the Signs. Act Early.”
The new report showed that boys were nearly twice as likely as girls to have any developmental delay, a pattern that was magnified when looking specifically at autism diagnoses. Boys were more than three times as likely as girls to be diagnosed with autism spectrum disorder. The rate of autism among boys was 4.7%, compared with 1.5% among girls.
While these latest survey results showed consistent rates of autism from 2019 to 2021, a different CDC report earlier this year showed an alarming jump in the rate of autism spectrum disorder among 8-year-olds. That report, which compared data from 2008 to 2020, showed the rate of autism among 8-year-olds rose during those 12 years from 1 in 88 kids to 1 in 36 kids.
The two analyses also differed in their findings regarding prevalence of autism when looking at children by race and ethnicity. The report from earlier this year showed that Black and Hispanic children were more likely to be diagnosed with autism, compared with White children. This latest report did not find any differences in the prevalence of autism based on a child’s race or ethnicity.
A version of this article appeared on WebMD.com.
FDA approves cognitive-behavioral app for adults with type 2 diabetes
A smartphone-based app designed to deliver cognitive-behavioral therapy (CBT) to adults with type 2 diabetes received marketing approval as a class II medical device from the Food and Drug Administration on July 10, becoming the first digital behavioral therapeutic device for people with diabetes to receive this designation for U.S. patients.
Better Therapeutics representatives said that the app, formerly known as BT-001, will be called AspyreRX, with U.S. sales planned to launch in October-December 2023.
The app will be available to patients exclusively by prescription, with a planned 90-day use duration and an option for a second 90-day prescription. A company official said the price per prescription will be about $500-800, although this is not yet finalized. The app is intended for use in concert with the conventional pillars of glycemic control in people with type 2 diabetes: lifestyle modification and treatment with antidiabetes medications.
Senior staff members of Better Therapeutics acknowledged the critical need for an education program, which they will now launch for clinicians, payers, and patients to get across the message of the potential benefit and safety associated with using the CBT app. Their initial marketing will target patients with type 2 diabetes and poorly controlled hemoglobin A1c levels in five to six U.S. regions with high numbers of these patients. The company will also attempt to make the app available through the Department of Veterans Affairs health system and try to secure coverage by Medicare and commercial health-insurance providers.
Approval based on pivotal trial results
The FDA approval focused on data collected in the BT-001 randomized, controlled trial, which included 669 U.S. adults with poorly controlled type 2 diabetes. Results, published in 2022 in Diabetes Care, showed that after 90 days, people using the app had an average incremental reduction in A1c of 0.39 percentage points, compared with control patients who didn’t use the app, the primary endpoint. Use of the app also appeared safe.
Subsequent meeting presentations of study findings showed that A1c-lowering linked with app use was durable during continued use for a total of 180 days, that the effectiveness of the app in helping to lower A1c levels was “dose dependent” relative to the number of lessons a person completed, and that using the app significantly linked with a reduced need for intensified glycemic control through added medications.
Another finding of the extended-use phase of the study was that 81% of patients assigned to the app-using group continued to regularly use the app after 180 days, a level of durable engagement by patients that “exceeded our expectations,” said Diane Gomez-Thinnes, chief commercial officer of Better Therapeutics, during a press conference.
The company plans to tweak the app prior to its launch based on additional analyses of results from the pivotal study to further improve patient engagement and app ease of use. The company is also planning to expand the range of smartphones that can support the app, although about 90%-95% of U.S. smartphones have this capability.
Better Therapeutics is also actively developing and testing other modifications to the basic CBT app to make it usable by people with other cardiometabolic disorders such as hypertension, obesity, and fatty liver disease.
The BT-001 study was funded by Better Therapeutics.
A version of this article first appeared on Medscape.com.
A smartphone-based app designed to deliver cognitive-behavioral therapy (CBT) to adults with type 2 diabetes received marketing approval as a class II medical device from the Food and Drug Administration on July 10, becoming the first digital behavioral therapeutic device for people with diabetes to receive this designation for U.S. patients.
Better Therapeutics representatives said that the app, formerly known as BT-001, will be called AspyreRX, with U.S. sales planned to launch in October-December 2023.
The app will be available to patients exclusively by prescription, with a planned 90-day use duration and an option for a second 90-day prescription. A company official said the price per prescription will be about $500-800, although this is not yet finalized. The app is intended for use in concert with the conventional pillars of glycemic control in people with type 2 diabetes: lifestyle modification and treatment with antidiabetes medications.
Senior staff members of Better Therapeutics acknowledged the critical need for an education program, which they will now launch for clinicians, payers, and patients to get across the message of the potential benefit and safety associated with using the CBT app. Their initial marketing will target patients with type 2 diabetes and poorly controlled hemoglobin A1c levels in five to six U.S. regions with high numbers of these patients. The company will also attempt to make the app available through the Department of Veterans Affairs health system and try to secure coverage by Medicare and commercial health-insurance providers.
Approval based on pivotal trial results
The FDA approval focused on data collected in the BT-001 randomized, controlled trial, which included 669 U.S. adults with poorly controlled type 2 diabetes. Results, published in 2022 in Diabetes Care, showed that after 90 days, people using the app had an average incremental reduction in A1c of 0.39 percentage points, compared with control patients who didn’t use the app, the primary endpoint. Use of the app also appeared safe.
Subsequent meeting presentations of study findings showed that A1c-lowering linked with app use was durable during continued use for a total of 180 days, that the effectiveness of the app in helping to lower A1c levels was “dose dependent” relative to the number of lessons a person completed, and that using the app significantly linked with a reduced need for intensified glycemic control through added medications.
Another finding of the extended-use phase of the study was that 81% of patients assigned to the app-using group continued to regularly use the app after 180 days, a level of durable engagement by patients that “exceeded our expectations,” said Diane Gomez-Thinnes, chief commercial officer of Better Therapeutics, during a press conference.
The company plans to tweak the app prior to its launch based on additional analyses of results from the pivotal study to further improve patient engagement and app ease of use. The company is also planning to expand the range of smartphones that can support the app, although about 90%-95% of U.S. smartphones have this capability.
Better Therapeutics is also actively developing and testing other modifications to the basic CBT app to make it usable by people with other cardiometabolic disorders such as hypertension, obesity, and fatty liver disease.
The BT-001 study was funded by Better Therapeutics.
A version of this article first appeared on Medscape.com.
A smartphone-based app designed to deliver cognitive-behavioral therapy (CBT) to adults with type 2 diabetes received marketing approval as a class II medical device from the Food and Drug Administration on July 10, becoming the first digital behavioral therapeutic device for people with diabetes to receive this designation for U.S. patients.
Better Therapeutics representatives said that the app, formerly known as BT-001, will be called AspyreRX, with U.S. sales planned to launch in October-December 2023.
The app will be available to patients exclusively by prescription, with a planned 90-day use duration and an option for a second 90-day prescription. A company official said the price per prescription will be about $500-800, although this is not yet finalized. The app is intended for use in concert with the conventional pillars of glycemic control in people with type 2 diabetes: lifestyle modification and treatment with antidiabetes medications.
Senior staff members of Better Therapeutics acknowledged the critical need for an education program, which they will now launch for clinicians, payers, and patients to get across the message of the potential benefit and safety associated with using the CBT app. Their initial marketing will target patients with type 2 diabetes and poorly controlled hemoglobin A1c levels in five to six U.S. regions with high numbers of these patients. The company will also attempt to make the app available through the Department of Veterans Affairs health system and try to secure coverage by Medicare and commercial health-insurance providers.
Approval based on pivotal trial results
The FDA approval focused on data collected in the BT-001 randomized, controlled trial, which included 669 U.S. adults with poorly controlled type 2 diabetes. Results, published in 2022 in Diabetes Care, showed that after 90 days, people using the app had an average incremental reduction in A1c of 0.39 percentage points, compared with control patients who didn’t use the app, the primary endpoint. Use of the app also appeared safe.
Subsequent meeting presentations of study findings showed that A1c-lowering linked with app use was durable during continued use for a total of 180 days, that the effectiveness of the app in helping to lower A1c levels was “dose dependent” relative to the number of lessons a person completed, and that using the app significantly linked with a reduced need for intensified glycemic control through added medications.
Another finding of the extended-use phase of the study was that 81% of patients assigned to the app-using group continued to regularly use the app after 180 days, a level of durable engagement by patients that “exceeded our expectations,” said Diane Gomez-Thinnes, chief commercial officer of Better Therapeutics, during a press conference.
The company plans to tweak the app prior to its launch based on additional analyses of results from the pivotal study to further improve patient engagement and app ease of use. The company is also planning to expand the range of smartphones that can support the app, although about 90%-95% of U.S. smartphones have this capability.
Better Therapeutics is also actively developing and testing other modifications to the basic CBT app to make it usable by people with other cardiometabolic disorders such as hypertension, obesity, and fatty liver disease.
The BT-001 study was funded by Better Therapeutics.
A version of this article first appeared on Medscape.com.
FDA expands inclisiran statin-adjunct indication to include primary prevention
Novartis has announced.
The first-in-class small interfering RNA (siRNA) agent was approved in 2021 as an adjunct to statins for patients with clinical cardiovascular disease or heterozygous familial hypercholesterolemia. The indications now include patients taking statins for primary dyslipidemia who have high-risk comorbidities such as diabetes but who do not have a history of cardiovascular events, the company said.
Inclisiran, with a mechanism of action unique among drugs for dyslipidemia, works by “silencing” RNA involved in the synthesis of proprotein convertase subtilisin/kexin type 9. The protein helps regulate the number of LDL cholesterol cell-surface receptors.
Novartis said it has “global rights to develop, manufacture and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals.”
A version of this article first appeared on Medscape.com.
Novartis has announced.
The first-in-class small interfering RNA (siRNA) agent was approved in 2021 as an adjunct to statins for patients with clinical cardiovascular disease or heterozygous familial hypercholesterolemia. The indications now include patients taking statins for primary dyslipidemia who have high-risk comorbidities such as diabetes but who do not have a history of cardiovascular events, the company said.
Inclisiran, with a mechanism of action unique among drugs for dyslipidemia, works by “silencing” RNA involved in the synthesis of proprotein convertase subtilisin/kexin type 9. The protein helps regulate the number of LDL cholesterol cell-surface receptors.
Novartis said it has “global rights to develop, manufacture and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals.”
A version of this article first appeared on Medscape.com.
Novartis has announced.
The first-in-class small interfering RNA (siRNA) agent was approved in 2021 as an adjunct to statins for patients with clinical cardiovascular disease or heterozygous familial hypercholesterolemia. The indications now include patients taking statins for primary dyslipidemia who have high-risk comorbidities such as diabetes but who do not have a history of cardiovascular events, the company said.
Inclisiran, with a mechanism of action unique among drugs for dyslipidemia, works by “silencing” RNA involved in the synthesis of proprotein convertase subtilisin/kexin type 9. The protein helps regulate the number of LDL cholesterol cell-surface receptors.
Novartis said it has “global rights to develop, manufacture and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals.”
A version of this article first appeared on Medscape.com.
FDA adds safety-related information to its dermal filler webpage
On July 6, the .
Along with a list of common reactions such as bruising, redness, swelling, and pain, the webpage now includes language to inform the public and health care providers about reports of delayed-onset inflammation that have been reported to occur near the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. According to an FDA spokesperson, the update is based on several sources of information, including postmarketing data from adverse event–reporting databases, such as the Manufacturer and User Facility Device Experience (MAUDE) for devices and the Vaccine Adverse Event Reporting System (VAERS) for vaccines, published literature, and recommendations from federal agencies and professional societies.
“More specifically, the site was updated to include certain risks of using dermal fillers such as swelling and bruising as well as some less common risks such as inflammation – swelling or redness near the dermal filler injection site – following viral or bacterial illnesses or infections, vaccinations, or dental procedures,” the spokesperson said.
The announcement about the update also states that “typically, the reported inflammation is responsive to treatment or resolves on its own.”
Other less common risks from dermal filler use listed on the website include bumps in or under the skin (nodules or granulomas) that may need to be treated with injections, oral antibiotics, or surgical removal; infection; open or draining wounds; a sore at the injection site; allergic reactions; or necrosis.
Meanwhile, rare risks from dermal filler use that have been reported to the FDA include severe allergic reactions (anaphylactic shock) that require immediate emergency medical assistance; migration (movement of filler material from the site of injection); leakage or rupture of the filler material at the injection site or through the skin (which may result from a tissue reaction or an infection); the formation of permanent hard nodules; and injury to the blood supply after an unintentional injection into a blood vessel, resulting in necrosis, vision abnormalities (including blindness), or stroke.
Lawrence J. Green, MD, of the department of dermatology at George Washington University, Washington, who was asked to comment about the FDA update on dermal fillers, said that the agency “is doing its job by making consumers aware of all possible complications [common and uncommon], as it does when it creates a package insert for a medication. Fortunately, however, comprehensive reviews published in the peer-reviewed dermatology literature show delayed inflammation to be a very rare event. So, while it is important for dermatologists during informed consent – prior to filler – to discuss that redness and/or nodules after infection/vaccinations, etc. are possible, it is important to add that based on the data, they are also highly unlikely.”
Sue Ellen Cox, MD, a dermatologist who practices in Chapel Hill, N.C., said that she was glad to see separate sections of recommendations geared to patients and health care providers. For example, the website recommends that patients seek a physician in the field of dermatology or plastic surgery to perform procedures that use dermal fillers. “These are not procedures to be done in an unsupervised spa setting,” said Dr. Cox, a past president of the American Society for Dermatologic Surgery and one of the task force authors of recommendations on preventing and treating adverse events of injectable fillers.
“It also makes the point of using products that are acquired from FDA-approved manufacturers, not products sold online or bootlegged from other countries. Finally, it goes into detail about the importance of in-depth knowledge of anatomy, which is crucial for safe injections and reviews potential complications such as intravascular events and hypersensitivity reactions. The administering physician should have extensive knowledge regarding how to treat any potential problems that arise.”
Dr. Green disclosed that he is a speaker, consultant, or investigator for many pharmaceutical companies. Dr. Cox disclosed that she has been a clinical investigator for many injectable companies including AbbVie, Galderma, Revance, and Chroma.
Health care professionals, patients, and others can report adverse events related to dermal fillers and other medical devices to the FDA at 800-FDA-1088 or on the MAUDE website.
On July 6, the .
Along with a list of common reactions such as bruising, redness, swelling, and pain, the webpage now includes language to inform the public and health care providers about reports of delayed-onset inflammation that have been reported to occur near the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. According to an FDA spokesperson, the update is based on several sources of information, including postmarketing data from adverse event–reporting databases, such as the Manufacturer and User Facility Device Experience (MAUDE) for devices and the Vaccine Adverse Event Reporting System (VAERS) for vaccines, published literature, and recommendations from federal agencies and professional societies.
“More specifically, the site was updated to include certain risks of using dermal fillers such as swelling and bruising as well as some less common risks such as inflammation – swelling or redness near the dermal filler injection site – following viral or bacterial illnesses or infections, vaccinations, or dental procedures,” the spokesperson said.
The announcement about the update also states that “typically, the reported inflammation is responsive to treatment or resolves on its own.”
Other less common risks from dermal filler use listed on the website include bumps in or under the skin (nodules or granulomas) that may need to be treated with injections, oral antibiotics, or surgical removal; infection; open or draining wounds; a sore at the injection site; allergic reactions; or necrosis.
Meanwhile, rare risks from dermal filler use that have been reported to the FDA include severe allergic reactions (anaphylactic shock) that require immediate emergency medical assistance; migration (movement of filler material from the site of injection); leakage or rupture of the filler material at the injection site or through the skin (which may result from a tissue reaction or an infection); the formation of permanent hard nodules; and injury to the blood supply after an unintentional injection into a blood vessel, resulting in necrosis, vision abnormalities (including blindness), or stroke.
Lawrence J. Green, MD, of the department of dermatology at George Washington University, Washington, who was asked to comment about the FDA update on dermal fillers, said that the agency “is doing its job by making consumers aware of all possible complications [common and uncommon], as it does when it creates a package insert for a medication. Fortunately, however, comprehensive reviews published in the peer-reviewed dermatology literature show delayed inflammation to be a very rare event. So, while it is important for dermatologists during informed consent – prior to filler – to discuss that redness and/or nodules after infection/vaccinations, etc. are possible, it is important to add that based on the data, they are also highly unlikely.”
Sue Ellen Cox, MD, a dermatologist who practices in Chapel Hill, N.C., said that she was glad to see separate sections of recommendations geared to patients and health care providers. For example, the website recommends that patients seek a physician in the field of dermatology or plastic surgery to perform procedures that use dermal fillers. “These are not procedures to be done in an unsupervised spa setting,” said Dr. Cox, a past president of the American Society for Dermatologic Surgery and one of the task force authors of recommendations on preventing and treating adverse events of injectable fillers.
“It also makes the point of using products that are acquired from FDA-approved manufacturers, not products sold online or bootlegged from other countries. Finally, it goes into detail about the importance of in-depth knowledge of anatomy, which is crucial for safe injections and reviews potential complications such as intravascular events and hypersensitivity reactions. The administering physician should have extensive knowledge regarding how to treat any potential problems that arise.”
Dr. Green disclosed that he is a speaker, consultant, or investigator for many pharmaceutical companies. Dr. Cox disclosed that she has been a clinical investigator for many injectable companies including AbbVie, Galderma, Revance, and Chroma.
Health care professionals, patients, and others can report adverse events related to dermal fillers and other medical devices to the FDA at 800-FDA-1088 or on the MAUDE website.
On July 6, the .
Along with a list of common reactions such as bruising, redness, swelling, and pain, the webpage now includes language to inform the public and health care providers about reports of delayed-onset inflammation that have been reported to occur near the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. According to an FDA spokesperson, the update is based on several sources of information, including postmarketing data from adverse event–reporting databases, such as the Manufacturer and User Facility Device Experience (MAUDE) for devices and the Vaccine Adverse Event Reporting System (VAERS) for vaccines, published literature, and recommendations from federal agencies and professional societies.
“More specifically, the site was updated to include certain risks of using dermal fillers such as swelling and bruising as well as some less common risks such as inflammation – swelling or redness near the dermal filler injection site – following viral or bacterial illnesses or infections, vaccinations, or dental procedures,” the spokesperson said.
The announcement about the update also states that “typically, the reported inflammation is responsive to treatment or resolves on its own.”
Other less common risks from dermal filler use listed on the website include bumps in or under the skin (nodules or granulomas) that may need to be treated with injections, oral antibiotics, or surgical removal; infection; open or draining wounds; a sore at the injection site; allergic reactions; or necrosis.
Meanwhile, rare risks from dermal filler use that have been reported to the FDA include severe allergic reactions (anaphylactic shock) that require immediate emergency medical assistance; migration (movement of filler material from the site of injection); leakage or rupture of the filler material at the injection site or through the skin (which may result from a tissue reaction or an infection); the formation of permanent hard nodules; and injury to the blood supply after an unintentional injection into a blood vessel, resulting in necrosis, vision abnormalities (including blindness), or stroke.
Lawrence J. Green, MD, of the department of dermatology at George Washington University, Washington, who was asked to comment about the FDA update on dermal fillers, said that the agency “is doing its job by making consumers aware of all possible complications [common and uncommon], as it does when it creates a package insert for a medication. Fortunately, however, comprehensive reviews published in the peer-reviewed dermatology literature show delayed inflammation to be a very rare event. So, while it is important for dermatologists during informed consent – prior to filler – to discuss that redness and/or nodules after infection/vaccinations, etc. are possible, it is important to add that based on the data, they are also highly unlikely.”
Sue Ellen Cox, MD, a dermatologist who practices in Chapel Hill, N.C., said that she was glad to see separate sections of recommendations geared to patients and health care providers. For example, the website recommends that patients seek a physician in the field of dermatology or plastic surgery to perform procedures that use dermal fillers. “These are not procedures to be done in an unsupervised spa setting,” said Dr. Cox, a past president of the American Society for Dermatologic Surgery and one of the task force authors of recommendations on preventing and treating adverse events of injectable fillers.
“It also makes the point of using products that are acquired from FDA-approved manufacturers, not products sold online or bootlegged from other countries. Finally, it goes into detail about the importance of in-depth knowledge of anatomy, which is crucial for safe injections and reviews potential complications such as intravascular events and hypersensitivity reactions. The administering physician should have extensive knowledge regarding how to treat any potential problems that arise.”
Dr. Green disclosed that he is a speaker, consultant, or investigator for many pharmaceutical companies. Dr. Cox disclosed that she has been a clinical investigator for many injectable companies including AbbVie, Galderma, Revance, and Chroma.
Health care professionals, patients, and others can report adverse events related to dermal fillers and other medical devices to the FDA at 800-FDA-1088 or on the MAUDE website.
Nearly one in five in U.S. still hadn’t gotten COVID by end of 2022
, according to a new estimate.
The findings came from an analysis of blood donations. The Centers for Disease Control and Prevention analyzed donor blood from 143,000 people every 3 months during 2022, looking for the presence of COVID antibodies that meant a person had previously been infected with the virus. The prevalence of antibodies from previous infections steadily rose throughout the year. Antibodies from prior infection were found in 49% of donors as of Feb. 15, 2022, 59% of donors as of May 15, 2022, 70% of donors as of Aug. 15, 2022, and 78% of donors as of Nov. 15, 2022.
Donor blood also was analyzed for the presence of antibodies known to come from COVID vaccination. When the vaccine-induced and infection-induced antibody data were combined, the CDC estimated that 97% of people had antibodies as of the end of the 2022.
In the report, CDC authors explained that while the presence of antibodies is related to protection from infection and to less severe disease, the level of antibodies that a person has can vary. The authors said that no standards have yet been set that show a minimum level of antibodies needed to provide protection.
As of July 3, more than 1.1 million people had died in the United States from COVID-19, according to CDC data. Deaths for the first half of 2023 are down dramatically, compared with the first 3 years of the pandemic, with just 41,538 death certificates this year listing the virus as an underlying or contributing cause. About two in three COVID deaths this year occurred in a hospital or nursing home, and 89% of people who died from the virus this year have been age 65 or older.
A version of this article first appeared on WebMD.com.
, according to a new estimate.
The findings came from an analysis of blood donations. The Centers for Disease Control and Prevention analyzed donor blood from 143,000 people every 3 months during 2022, looking for the presence of COVID antibodies that meant a person had previously been infected with the virus. The prevalence of antibodies from previous infections steadily rose throughout the year. Antibodies from prior infection were found in 49% of donors as of Feb. 15, 2022, 59% of donors as of May 15, 2022, 70% of donors as of Aug. 15, 2022, and 78% of donors as of Nov. 15, 2022.
Donor blood also was analyzed for the presence of antibodies known to come from COVID vaccination. When the vaccine-induced and infection-induced antibody data were combined, the CDC estimated that 97% of people had antibodies as of the end of the 2022.
In the report, CDC authors explained that while the presence of antibodies is related to protection from infection and to less severe disease, the level of antibodies that a person has can vary. The authors said that no standards have yet been set that show a minimum level of antibodies needed to provide protection.
As of July 3, more than 1.1 million people had died in the United States from COVID-19, according to CDC data. Deaths for the first half of 2023 are down dramatically, compared with the first 3 years of the pandemic, with just 41,538 death certificates this year listing the virus as an underlying or contributing cause. About two in three COVID deaths this year occurred in a hospital or nursing home, and 89% of people who died from the virus this year have been age 65 or older.
A version of this article first appeared on WebMD.com.
, according to a new estimate.
The findings came from an analysis of blood donations. The Centers for Disease Control and Prevention analyzed donor blood from 143,000 people every 3 months during 2022, looking for the presence of COVID antibodies that meant a person had previously been infected with the virus. The prevalence of antibodies from previous infections steadily rose throughout the year. Antibodies from prior infection were found in 49% of donors as of Feb. 15, 2022, 59% of donors as of May 15, 2022, 70% of donors as of Aug. 15, 2022, and 78% of donors as of Nov. 15, 2022.
Donor blood also was analyzed for the presence of antibodies known to come from COVID vaccination. When the vaccine-induced and infection-induced antibody data were combined, the CDC estimated that 97% of people had antibodies as of the end of the 2022.
In the report, CDC authors explained that while the presence of antibodies is related to protection from infection and to less severe disease, the level of antibodies that a person has can vary. The authors said that no standards have yet been set that show a minimum level of antibodies needed to provide protection.
As of July 3, more than 1.1 million people had died in the United States from COVID-19, according to CDC data. Deaths for the first half of 2023 are down dramatically, compared with the first 3 years of the pandemic, with just 41,538 death certificates this year listing the virus as an underlying or contributing cause. About two in three COVID deaths this year occurred in a hospital or nursing home, and 89% of people who died from the virus this year have been age 65 or older.
A version of this article first appeared on WebMD.com.
FDA approves first gene therapy for hemophilia A
Valoctocogene roxaparvovec, a one-time, single-dose IV infusion, is the first gene therapy approved in the United States for severe hemophilia A and will cost around $2.9 million. BioMarin has said the price tag reflects “the possibility of freedom from years” of infusions, which come to about $800,000 each year.
However, last December, the Institute for Clinical and Economic Review (ICER) set the upper bounds for the gene therapy at about $1.96 million. The extent to which the gene therapy will provide freedom from infusions, for how long, and in which patients are not completely understood.
Hemophilia A is caused by a mutation in the gene that produces a protein called coagulation factor VIII, which is essential for blood clotting. Valoctocogene roxaparvovec delivers a functional gene to liver cells via an adeno-associated virus serotype 5; the gene instructs the cells to make the missing clotting factor.
“Adults with severe hemophilia A face a lifelong burden, with frequent infusions and a high risk of health complications, including uncontrolled bleeding and irreversible joint damage,” Steven Pipe, MD, professor of pediatrics and pathology at the University of Michigan, Ann Arbor, and an investigator for the phase 3 study that led to the approval, said in a statement. The approval of valoctocogene roxaparvovec “has the potential to transform the way we treat adults based on years of bleed control following a single, one-time infusion.”
About 6,500 U.S. adults live with severe hemophilia A, and BioMarin said it anticipates approximately 2,500 will be eligible to receive the gene therapy following the approval. The U.S. indication is limited to patients without a history of factor VIII inhibitors and without detectable antibodies to the adeno-associated virus serotype 5.
Last August, the European Medicines Agency authorized the gene therapy for use in Europe, but according to Forbes and PharmaPhorum, uptake in Europe has been delayed because of reimbursement issues, given the cost of treatment and clinical uncertainties.
Data to date, however, are promising for most patients. Approval was based on BioMarin’s open-label, single-arm GENEr8-1 study in 134 men with severe congenital hemophilia A. Patients received a single infusion of 6 x 1013 vector genomes per kilogram.
Among the 132 patients available for 2-year evaluation, median factor VIII activity was in the range for mild hemophilia (6%-39% of normal) with an 84.5% reduction in bleeding events from baseline.
More than 80% of participants had no bleeding events requiring treatment, and there was a 98% reduction from baseline in mean use of exogenous factor VIII.
Overall, at 2 years, only 4.5% of patients had factor VIII activity consistent with severe hemophilia A; 9.1% had activity consistent with moderate disease; 59.8% had activity consistent with mild disease, and 26.5% had activity in the normal range above 40 IU/dL.
Trial investigators estimated that the typical half-life of the transgene-derived factor VIII production system is 123 weeks.
Among the six men who resumed prophylaxis, most had fewer bleeding events than when they were on prophylaxis before the infusion. All patients developed antibodies to the virus delivery vector, precluding retreatment.
Elevated alanine aminotransferase levels were the most common adverse event, occurring in 88.8% of patients, who were treated with immunosuppressants for a median of 33 weeks. Elevations persisted at 2 years in 29% of patients.
The other most common adverse events were headache (38.1%), nausea (37.3%), and increases in aspartate aminotransferase (35.1%).
A version of this article first appeared on Medscape.com.
Valoctocogene roxaparvovec, a one-time, single-dose IV infusion, is the first gene therapy approved in the United States for severe hemophilia A and will cost around $2.9 million. BioMarin has said the price tag reflects “the possibility of freedom from years” of infusions, which come to about $800,000 each year.
However, last December, the Institute for Clinical and Economic Review (ICER) set the upper bounds for the gene therapy at about $1.96 million. The extent to which the gene therapy will provide freedom from infusions, for how long, and in which patients are not completely understood.
Hemophilia A is caused by a mutation in the gene that produces a protein called coagulation factor VIII, which is essential for blood clotting. Valoctocogene roxaparvovec delivers a functional gene to liver cells via an adeno-associated virus serotype 5; the gene instructs the cells to make the missing clotting factor.
“Adults with severe hemophilia A face a lifelong burden, with frequent infusions and a high risk of health complications, including uncontrolled bleeding and irreversible joint damage,” Steven Pipe, MD, professor of pediatrics and pathology at the University of Michigan, Ann Arbor, and an investigator for the phase 3 study that led to the approval, said in a statement. The approval of valoctocogene roxaparvovec “has the potential to transform the way we treat adults based on years of bleed control following a single, one-time infusion.”
About 6,500 U.S. adults live with severe hemophilia A, and BioMarin said it anticipates approximately 2,500 will be eligible to receive the gene therapy following the approval. The U.S. indication is limited to patients without a history of factor VIII inhibitors and without detectable antibodies to the adeno-associated virus serotype 5.
Last August, the European Medicines Agency authorized the gene therapy for use in Europe, but according to Forbes and PharmaPhorum, uptake in Europe has been delayed because of reimbursement issues, given the cost of treatment and clinical uncertainties.
Data to date, however, are promising for most patients. Approval was based on BioMarin’s open-label, single-arm GENEr8-1 study in 134 men with severe congenital hemophilia A. Patients received a single infusion of 6 x 1013 vector genomes per kilogram.
Among the 132 patients available for 2-year evaluation, median factor VIII activity was in the range for mild hemophilia (6%-39% of normal) with an 84.5% reduction in bleeding events from baseline.
More than 80% of participants had no bleeding events requiring treatment, and there was a 98% reduction from baseline in mean use of exogenous factor VIII.
Overall, at 2 years, only 4.5% of patients had factor VIII activity consistent with severe hemophilia A; 9.1% had activity consistent with moderate disease; 59.8% had activity consistent with mild disease, and 26.5% had activity in the normal range above 40 IU/dL.
Trial investigators estimated that the typical half-life of the transgene-derived factor VIII production system is 123 weeks.
Among the six men who resumed prophylaxis, most had fewer bleeding events than when they were on prophylaxis before the infusion. All patients developed antibodies to the virus delivery vector, precluding retreatment.
Elevated alanine aminotransferase levels were the most common adverse event, occurring in 88.8% of patients, who were treated with immunosuppressants for a median of 33 weeks. Elevations persisted at 2 years in 29% of patients.
The other most common adverse events were headache (38.1%), nausea (37.3%), and increases in aspartate aminotransferase (35.1%).
A version of this article first appeared on Medscape.com.
Valoctocogene roxaparvovec, a one-time, single-dose IV infusion, is the first gene therapy approved in the United States for severe hemophilia A and will cost around $2.9 million. BioMarin has said the price tag reflects “the possibility of freedom from years” of infusions, which come to about $800,000 each year.
However, last December, the Institute for Clinical and Economic Review (ICER) set the upper bounds for the gene therapy at about $1.96 million. The extent to which the gene therapy will provide freedom from infusions, for how long, and in which patients are not completely understood.
Hemophilia A is caused by a mutation in the gene that produces a protein called coagulation factor VIII, which is essential for blood clotting. Valoctocogene roxaparvovec delivers a functional gene to liver cells via an adeno-associated virus serotype 5; the gene instructs the cells to make the missing clotting factor.
“Adults with severe hemophilia A face a lifelong burden, with frequent infusions and a high risk of health complications, including uncontrolled bleeding and irreversible joint damage,” Steven Pipe, MD, professor of pediatrics and pathology at the University of Michigan, Ann Arbor, and an investigator for the phase 3 study that led to the approval, said in a statement. The approval of valoctocogene roxaparvovec “has the potential to transform the way we treat adults based on years of bleed control following a single, one-time infusion.”
About 6,500 U.S. adults live with severe hemophilia A, and BioMarin said it anticipates approximately 2,500 will be eligible to receive the gene therapy following the approval. The U.S. indication is limited to patients without a history of factor VIII inhibitors and without detectable antibodies to the adeno-associated virus serotype 5.
Last August, the European Medicines Agency authorized the gene therapy for use in Europe, but according to Forbes and PharmaPhorum, uptake in Europe has been delayed because of reimbursement issues, given the cost of treatment and clinical uncertainties.
Data to date, however, are promising for most patients. Approval was based on BioMarin’s open-label, single-arm GENEr8-1 study in 134 men with severe congenital hemophilia A. Patients received a single infusion of 6 x 1013 vector genomes per kilogram.
Among the 132 patients available for 2-year evaluation, median factor VIII activity was in the range for mild hemophilia (6%-39% of normal) with an 84.5% reduction in bleeding events from baseline.
More than 80% of participants had no bleeding events requiring treatment, and there was a 98% reduction from baseline in mean use of exogenous factor VIII.
Overall, at 2 years, only 4.5% of patients had factor VIII activity consistent with severe hemophilia A; 9.1% had activity consistent with moderate disease; 59.8% had activity consistent with mild disease, and 26.5% had activity in the normal range above 40 IU/dL.
Trial investigators estimated that the typical half-life of the transgene-derived factor VIII production system is 123 weeks.
Among the six men who resumed prophylaxis, most had fewer bleeding events than when they were on prophylaxis before the infusion. All patients developed antibodies to the virus delivery vector, precluding retreatment.
Elevated alanine aminotransferase levels were the most common adverse event, occurring in 88.8% of patients, who were treated with immunosuppressants for a median of 33 weeks. Elevations persisted at 2 years in 29% of patients.
The other most common adverse events were headache (38.1%), nausea (37.3%), and increases in aspartate aminotransferase (35.1%).
A version of this article first appeared on Medscape.com.