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FDA approves pembrolizumab for sorafenib-intolerant HCC patients
The Food and Drug Administration has approved pembrolizumab (Keytruda) for the treatment of patients with hepatocellular carcinoma who were previously treated with sorafenib.
Approval was based on results of KEYNOTE-224, a single-arm, open-label, multicenter trial evaluating pembrolizumab in a group of 104 patients with hepatocellular carcinoma who were either intolerant to or had disease progression with sorafenib, according to a company press release.
The objective response rate was 17%, with a complete response rate of 1% and a partial response rate of 16%. In responding patients, 89% had a response duration of at least 6 months, and 56% had a response duration of at least 12 months.
Adverse events were generally similar to those seen in trials of patients with melanoma or non–small cell lung cancer, and included pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and allogeneic hematopoietic stem cell transplantation complications.
“Hepatocellular carcinoma is the most common type of liver cancer in adults, and while we have seen recent therapeutic advancements, there are still limited treatment options for advanced recurrent disease. Today’s approval of Keytruda is important, as it provides a new treatment option for patients with hepatocellular carcinoma who have been previously treated with sorafenib,” Andrew X. Zhu, MD, lead investigator and director of liver cancer research at Massachusetts General Hospital and professor of medicine at Harvard Medical School, both in Boston, said in the press release.
The Food and Drug Administration has approved pembrolizumab (Keytruda) for the treatment of patients with hepatocellular carcinoma who were previously treated with sorafenib.
Approval was based on results of KEYNOTE-224, a single-arm, open-label, multicenter trial evaluating pembrolizumab in a group of 104 patients with hepatocellular carcinoma who were either intolerant to or had disease progression with sorafenib, according to a company press release.
The objective response rate was 17%, with a complete response rate of 1% and a partial response rate of 16%. In responding patients, 89% had a response duration of at least 6 months, and 56% had a response duration of at least 12 months.
Adverse events were generally similar to those seen in trials of patients with melanoma or non–small cell lung cancer, and included pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and allogeneic hematopoietic stem cell transplantation complications.
“Hepatocellular carcinoma is the most common type of liver cancer in adults, and while we have seen recent therapeutic advancements, there are still limited treatment options for advanced recurrent disease. Today’s approval of Keytruda is important, as it provides a new treatment option for patients with hepatocellular carcinoma who have been previously treated with sorafenib,” Andrew X. Zhu, MD, lead investigator and director of liver cancer research at Massachusetts General Hospital and professor of medicine at Harvard Medical School, both in Boston, said in the press release.
The Food and Drug Administration has approved pembrolizumab (Keytruda) for the treatment of patients with hepatocellular carcinoma who were previously treated with sorafenib.
Approval was based on results of KEYNOTE-224, a single-arm, open-label, multicenter trial evaluating pembrolizumab in a group of 104 patients with hepatocellular carcinoma who were either intolerant to or had disease progression with sorafenib, according to a company press release.
The objective response rate was 17%, with a complete response rate of 1% and a partial response rate of 16%. In responding patients, 89% had a response duration of at least 6 months, and 56% had a response duration of at least 12 months.
Adverse events were generally similar to those seen in trials of patients with melanoma or non–small cell lung cancer, and included pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and allogeneic hematopoietic stem cell transplantation complications.
“Hepatocellular carcinoma is the most common type of liver cancer in adults, and while we have seen recent therapeutic advancements, there are still limited treatment options for advanced recurrent disease. Today’s approval of Keytruda is important, as it provides a new treatment option for patients with hepatocellular carcinoma who have been previously treated with sorafenib,” Andrew X. Zhu, MD, lead investigator and director of liver cancer research at Massachusetts General Hospital and professor of medicine at Harvard Medical School, both in Boston, said in the press release.
P-BCMA-101 gains FDA regenerative medicine designation
(MM), has received the regenerative medicine advanced therapy (RMAT) designation from the Food and Drug Administration.
P-BCMA-101 modifies patients’ T cells using a nonviral DNA modification system known as piggyBac. The modified T cells target cells expressing B-cell maturation antigen (BCMA), which is expressed on essentially all MM cells.
Early results from the phase 1 clinical trial of P-BCMA-101 were recently reported at the 2018 CAR-TCR Summit by Eric Ostertag, MD, PhD, chief executive officer of Poseida Therapeutics, the company developing P-BCMA-101.
Initial results of the trial (NCT03288493) included data on 11 patients with heavily pretreated MM. Patients were a median age of 60, and 73% were high risk. They had a median of six prior therapies.
Patients received conditioning treatment with fludarabine and cyclophosphamide for 3 days prior to receiving P-BCMA-101. They then received one of three doses of CAR T cells – 51×106 (n=3), 152×106 (n=7), or 430×106 (n=1).
The investigators observed no dose-limiting toxicities. Adverse events included neutropenia in eight patients and thrombocytopenia in five.
One patient may have had cytokine release syndrome, but the condition resolved without drug intervention. And investigators observed no neurotoxicity.
Seven of ten patients evaluable for response by International Myeloma Working Group criteria achieved at least a partial response, including very good partial responses and stringent complete response.
The eleventh patient has oligosecretory disease and was only evaluable by PET, which indicated a near-complete response.
Poseida expects to have additional data to report by the end of the year, according to Dr. Ostertag. The study is funded by the California Institute for Regenerative Medicine and Poseida Therapeutics.RMAT designation is intended to expedite development and review of regenerative medicines that are intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition.
Preliminary evidence must indicate that the therapy has the potential to address unmet medical needs for the disease or condition. RMAT designation includes all the benefits of fast track and breakthrough therapy designations, including early interactions with the FDA.
(MM), has received the regenerative medicine advanced therapy (RMAT) designation from the Food and Drug Administration.
P-BCMA-101 modifies patients’ T cells using a nonviral DNA modification system known as piggyBac. The modified T cells target cells expressing B-cell maturation antigen (BCMA), which is expressed on essentially all MM cells.
Early results from the phase 1 clinical trial of P-BCMA-101 were recently reported at the 2018 CAR-TCR Summit by Eric Ostertag, MD, PhD, chief executive officer of Poseida Therapeutics, the company developing P-BCMA-101.
Initial results of the trial (NCT03288493) included data on 11 patients with heavily pretreated MM. Patients were a median age of 60, and 73% were high risk. They had a median of six prior therapies.
Patients received conditioning treatment with fludarabine and cyclophosphamide for 3 days prior to receiving P-BCMA-101. They then received one of three doses of CAR T cells – 51×106 (n=3), 152×106 (n=7), or 430×106 (n=1).
The investigators observed no dose-limiting toxicities. Adverse events included neutropenia in eight patients and thrombocytopenia in five.
One patient may have had cytokine release syndrome, but the condition resolved without drug intervention. And investigators observed no neurotoxicity.
Seven of ten patients evaluable for response by International Myeloma Working Group criteria achieved at least a partial response, including very good partial responses and stringent complete response.
The eleventh patient has oligosecretory disease and was only evaluable by PET, which indicated a near-complete response.
Poseida expects to have additional data to report by the end of the year, according to Dr. Ostertag. The study is funded by the California Institute for Regenerative Medicine and Poseida Therapeutics.RMAT designation is intended to expedite development and review of regenerative medicines that are intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition.
Preliminary evidence must indicate that the therapy has the potential to address unmet medical needs for the disease or condition. RMAT designation includes all the benefits of fast track and breakthrough therapy designations, including early interactions with the FDA.
(MM), has received the regenerative medicine advanced therapy (RMAT) designation from the Food and Drug Administration.
P-BCMA-101 modifies patients’ T cells using a nonviral DNA modification system known as piggyBac. The modified T cells target cells expressing B-cell maturation antigen (BCMA), which is expressed on essentially all MM cells.
Early results from the phase 1 clinical trial of P-BCMA-101 were recently reported at the 2018 CAR-TCR Summit by Eric Ostertag, MD, PhD, chief executive officer of Poseida Therapeutics, the company developing P-BCMA-101.
Initial results of the trial (NCT03288493) included data on 11 patients with heavily pretreated MM. Patients were a median age of 60, and 73% were high risk. They had a median of six prior therapies.
Patients received conditioning treatment with fludarabine and cyclophosphamide for 3 days prior to receiving P-BCMA-101. They then received one of three doses of CAR T cells – 51×106 (n=3), 152×106 (n=7), or 430×106 (n=1).
The investigators observed no dose-limiting toxicities. Adverse events included neutropenia in eight patients and thrombocytopenia in five.
One patient may have had cytokine release syndrome, but the condition resolved without drug intervention. And investigators observed no neurotoxicity.
Seven of ten patients evaluable for response by International Myeloma Working Group criteria achieved at least a partial response, including very good partial responses and stringent complete response.
The eleventh patient has oligosecretory disease and was only evaluable by PET, which indicated a near-complete response.
Poseida expects to have additional data to report by the end of the year, according to Dr. Ostertag. The study is funded by the California Institute for Regenerative Medicine and Poseida Therapeutics.RMAT designation is intended to expedite development and review of regenerative medicines that are intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition.
Preliminary evidence must indicate that the therapy has the potential to address unmet medical needs for the disease or condition. RMAT designation includes all the benefits of fast track and breakthrough therapy designations, including early interactions with the FDA.
FDA puts selinexor on fast track for DLBCL
The Food and Drug Administration has granted fast track designation to selinexor for the treatment of diffuse large B-cell lymphoma (DLBCL).
The designation is for selinexor to treat DLBCL patients who have received at least two prior therapies and who are not eligible for high-dose chemotherapy with stem cell rescue or chimeric antigen receptor (CAR) T-cell therapy.
Selinexor is being studied in the phase 2b SADAL trial (NCT02227251), which is enrolling patients with relapsed or refractory DLBCL who have received two to five prior therapies and are not eligible for stem cell transplant.
Top-line results from this trial are scheduled to be presented at the 2018 ASH Annual Meeting (Abstract 1677).
Selinexor is an oral selective inhibitor of nuclear export compound being developed by Karyopharm Therapeutics.
The company previously received fast track designation for selinexor to treat patients with penta-refractory multiple myeloma who have received at least three prior lines of therapy.
The FDA’s fast track program is designed to facilitate the development and expedite the review of products that are intended to treat serious conditions and have the potential to address unmet medical needs. Fast track designation provides developers with greater access to the FDA as well as eligibility for accelerated approval, priority review, and rolling review.
“Pending positive results from the phase 2b SADAL study, we plan to submit a second NDA [new drug application] to the FDA in the first half of 2019, with a request for accelerated approval, for oral selinexor as a potential new treatment for patients with relapsed or refractory DLBCL,” Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm, said in a statement.
In October, the FDA accepted an NDA for selinexor as a treatment for penta-refractory multiple myeloma. The agency granted the application priority review and set an action date of April 6, 2019.
The Food and Drug Administration has granted fast track designation to selinexor for the treatment of diffuse large B-cell lymphoma (DLBCL).
The designation is for selinexor to treat DLBCL patients who have received at least two prior therapies and who are not eligible for high-dose chemotherapy with stem cell rescue or chimeric antigen receptor (CAR) T-cell therapy.
Selinexor is being studied in the phase 2b SADAL trial (NCT02227251), which is enrolling patients with relapsed or refractory DLBCL who have received two to five prior therapies and are not eligible for stem cell transplant.
Top-line results from this trial are scheduled to be presented at the 2018 ASH Annual Meeting (Abstract 1677).
Selinexor is an oral selective inhibitor of nuclear export compound being developed by Karyopharm Therapeutics.
The company previously received fast track designation for selinexor to treat patients with penta-refractory multiple myeloma who have received at least three prior lines of therapy.
The FDA’s fast track program is designed to facilitate the development and expedite the review of products that are intended to treat serious conditions and have the potential to address unmet medical needs. Fast track designation provides developers with greater access to the FDA as well as eligibility for accelerated approval, priority review, and rolling review.
“Pending positive results from the phase 2b SADAL study, we plan to submit a second NDA [new drug application] to the FDA in the first half of 2019, with a request for accelerated approval, for oral selinexor as a potential new treatment for patients with relapsed or refractory DLBCL,” Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm, said in a statement.
In October, the FDA accepted an NDA for selinexor as a treatment for penta-refractory multiple myeloma. The agency granted the application priority review and set an action date of April 6, 2019.
The Food and Drug Administration has granted fast track designation to selinexor for the treatment of diffuse large B-cell lymphoma (DLBCL).
The designation is for selinexor to treat DLBCL patients who have received at least two prior therapies and who are not eligible for high-dose chemotherapy with stem cell rescue or chimeric antigen receptor (CAR) T-cell therapy.
Selinexor is being studied in the phase 2b SADAL trial (NCT02227251), which is enrolling patients with relapsed or refractory DLBCL who have received two to five prior therapies and are not eligible for stem cell transplant.
Top-line results from this trial are scheduled to be presented at the 2018 ASH Annual Meeting (Abstract 1677).
Selinexor is an oral selective inhibitor of nuclear export compound being developed by Karyopharm Therapeutics.
The company previously received fast track designation for selinexor to treat patients with penta-refractory multiple myeloma who have received at least three prior lines of therapy.
The FDA’s fast track program is designed to facilitate the development and expedite the review of products that are intended to treat serious conditions and have the potential to address unmet medical needs. Fast track designation provides developers with greater access to the FDA as well as eligibility for accelerated approval, priority review, and rolling review.
“Pending positive results from the phase 2b SADAL study, we plan to submit a second NDA [new drug application] to the FDA in the first half of 2019, with a request for accelerated approval, for oral selinexor as a potential new treatment for patients with relapsed or refractory DLBCL,” Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm, said in a statement.
In October, the FDA accepted an NDA for selinexor as a treatment for penta-refractory multiple myeloma. The agency granted the application priority review and set an action date of April 6, 2019.
Portable hematology analyzer gets FDA nod
The Food and Drug Administration has granted .
HemoScreen requires a single drop of blood and uses disposable cartridges that provide automatic sample preparation.
HemoScreen can analyze 20 standard complete blood count parameters and produces results within 5 minutes.
Study results suggested that HemoScreen provides results comparable to those of another hematology analyzer, Sysmex XE-2100 (J Clin Pathol. 2016 Aug;69[8]:720-5).
“The HemoScreen delivers lab accurate results,” Avishay Bransky, PhD, CEO of PixCell, said in a statement.
HemoScreen “would be especially useful” in physicians’ offices, emergency rooms, intensive care units, oncology clinics, and remote locations, he added.
HemoScreen makes use of a technology called viscoelastic focusing, which employs microfluidics and machine vision algorithms to analyze cells.
The Food and Drug Administration has granted .
HemoScreen requires a single drop of blood and uses disposable cartridges that provide automatic sample preparation.
HemoScreen can analyze 20 standard complete blood count parameters and produces results within 5 minutes.
Study results suggested that HemoScreen provides results comparable to those of another hematology analyzer, Sysmex XE-2100 (J Clin Pathol. 2016 Aug;69[8]:720-5).
“The HemoScreen delivers lab accurate results,” Avishay Bransky, PhD, CEO of PixCell, said in a statement.
HemoScreen “would be especially useful” in physicians’ offices, emergency rooms, intensive care units, oncology clinics, and remote locations, he added.
HemoScreen makes use of a technology called viscoelastic focusing, which employs microfluidics and machine vision algorithms to analyze cells.
The Food and Drug Administration has granted .
HemoScreen requires a single drop of blood and uses disposable cartridges that provide automatic sample preparation.
HemoScreen can analyze 20 standard complete blood count parameters and produces results within 5 minutes.
Study results suggested that HemoScreen provides results comparable to those of another hematology analyzer, Sysmex XE-2100 (J Clin Pathol. 2016 Aug;69[8]:720-5).
“The HemoScreen delivers lab accurate results,” Avishay Bransky, PhD, CEO of PixCell, said in a statement.
HemoScreen “would be especially useful” in physicians’ offices, emergency rooms, intensive care units, oncology clinics, and remote locations, he added.
HemoScreen makes use of a technology called viscoelastic focusing, which employs microfluidics and machine vision algorithms to analyze cells.
FDA accepts priority review of dupilumab for adolescent atopic dermatitis
The Food and Drug Administration has accepted the who have not been well controlled with topical therapies or who are unable to use topical therapies.
In a statement, dupilumab manufacturers Regeneron and Sanofi announced that the target action data for an FDA decision on dupilumab for adolescents is March 11, 2019. “Currently, there are no FDA-approved systemic biologic medicines to treat adolescents with moderate to severe atopic dermatitis,” the companies said in the statement.
The sBLA for dupilumab use in teens is based on data from a phase 3 study presented at the annual congress of European Academy of Dermatology and Venereology in September 2018. In that study, the proportion of patients who achieved a 75% or greater improvement in the Eczema Area and Severity Index at 16 weeks was 38.1% with monthly dupilumab, 41.5% with dupilumab every 2 weeks, and 8.2% with placebo.
According to the companies, the most common adverse events included injection site reactions, oropharyngeal pain, and cold sores. Conjunctivitis has also been reported in some patients.
Dupilumab (Dupixent), which inhibits interleukin-4 and interleukin-13 signaling, is currently approved for treating uncontrolled moderate to severe AD in adults and, more recently, as an add-on maintenance treatment in patients with moderate to severe asthma aged 12 years and older with an eosinophilic phenotype or with oral corticosteroid–dependent asthma.
The FDA granted Breakthrough Therapy designation for dupilumab in 2016 for the treatment of moderate to severe AD in adolescents and severe AD in children aged 6 months to 11 years who are insufficiently controlled with topical medications.
The Food and Drug Administration has accepted the who have not been well controlled with topical therapies or who are unable to use topical therapies.
In a statement, dupilumab manufacturers Regeneron and Sanofi announced that the target action data for an FDA decision on dupilumab for adolescents is March 11, 2019. “Currently, there are no FDA-approved systemic biologic medicines to treat adolescents with moderate to severe atopic dermatitis,” the companies said in the statement.
The sBLA for dupilumab use in teens is based on data from a phase 3 study presented at the annual congress of European Academy of Dermatology and Venereology in September 2018. In that study, the proportion of patients who achieved a 75% or greater improvement in the Eczema Area and Severity Index at 16 weeks was 38.1% with monthly dupilumab, 41.5% with dupilumab every 2 weeks, and 8.2% with placebo.
According to the companies, the most common adverse events included injection site reactions, oropharyngeal pain, and cold sores. Conjunctivitis has also been reported in some patients.
Dupilumab (Dupixent), which inhibits interleukin-4 and interleukin-13 signaling, is currently approved for treating uncontrolled moderate to severe AD in adults and, more recently, as an add-on maintenance treatment in patients with moderate to severe asthma aged 12 years and older with an eosinophilic phenotype or with oral corticosteroid–dependent asthma.
The FDA granted Breakthrough Therapy designation for dupilumab in 2016 for the treatment of moderate to severe AD in adolescents and severe AD in children aged 6 months to 11 years who are insufficiently controlled with topical medications.
The Food and Drug Administration has accepted the who have not been well controlled with topical therapies or who are unable to use topical therapies.
In a statement, dupilumab manufacturers Regeneron and Sanofi announced that the target action data for an FDA decision on dupilumab for adolescents is March 11, 2019. “Currently, there are no FDA-approved systemic biologic medicines to treat adolescents with moderate to severe atopic dermatitis,” the companies said in the statement.
The sBLA for dupilumab use in teens is based on data from a phase 3 study presented at the annual congress of European Academy of Dermatology and Venereology in September 2018. In that study, the proportion of patients who achieved a 75% or greater improvement in the Eczema Area and Severity Index at 16 weeks was 38.1% with monthly dupilumab, 41.5% with dupilumab every 2 weeks, and 8.2% with placebo.
According to the companies, the most common adverse events included injection site reactions, oropharyngeal pain, and cold sores. Conjunctivitis has also been reported in some patients.
Dupilumab (Dupixent), which inhibits interleukin-4 and interleukin-13 signaling, is currently approved for treating uncontrolled moderate to severe AD in adults and, more recently, as an add-on maintenance treatment in patients with moderate to severe asthma aged 12 years and older with an eosinophilic phenotype or with oral corticosteroid–dependent asthma.
The FDA granted Breakthrough Therapy designation for dupilumab in 2016 for the treatment of moderate to severe AD in adolescents and severe AD in children aged 6 months to 11 years who are insufficiently controlled with topical medications.
FDA approves elotuzumab with pom/dex in refractory myeloma
The who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
Elotuzumab is already approved in combination with lenalidomide and dexamethasone to treat adult myeloma patients who have received one to three prior therapies.
The FDA’s latest approval of elotuzumab is based on results from ELOQUENT-3. This phase 2 trial enrolled multiple myeloma patients who had refractory or relapsed disease and had received both lenalidomide and a proteasome inhibitor.
In the trial, patients were randomized to receive elotuzumab plus pomalidomide and dexamethasone (EPd, n = 60) or pomalidomide and dexamethasone (Pd, n = 57) in 28-day cycles until disease progression or unacceptable toxicity.
The overall response rate was 53.3% in the EPd arm and 26.3% in the Pd arm (P = .0029); the rate of complete response or stringent complete response was 8.3% and 1.8%, respectively.
Median progression-free survival was 10.25 months with EPd and 4.67 months with Pd (P = .0078).
Serious adverse events occurred in 22% of patients in the EPd arm and 15% in the Pd arm. The most frequent serious adverse events were pneumonia and respiratory tract infection.
Additional results from ELOQUENT-3 can be found in the full prescribing information for elotuzumab, which is available on the Empliciti website.
Bristol-Myers Squibb and AbbVie are codeveloping elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.
The who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
Elotuzumab is already approved in combination with lenalidomide and dexamethasone to treat adult myeloma patients who have received one to three prior therapies.
The FDA’s latest approval of elotuzumab is based on results from ELOQUENT-3. This phase 2 trial enrolled multiple myeloma patients who had refractory or relapsed disease and had received both lenalidomide and a proteasome inhibitor.
In the trial, patients were randomized to receive elotuzumab plus pomalidomide and dexamethasone (EPd, n = 60) or pomalidomide and dexamethasone (Pd, n = 57) in 28-day cycles until disease progression or unacceptable toxicity.
The overall response rate was 53.3% in the EPd arm and 26.3% in the Pd arm (P = .0029); the rate of complete response or stringent complete response was 8.3% and 1.8%, respectively.
Median progression-free survival was 10.25 months with EPd and 4.67 months with Pd (P = .0078).
Serious adverse events occurred in 22% of patients in the EPd arm and 15% in the Pd arm. The most frequent serious adverse events were pneumonia and respiratory tract infection.
Additional results from ELOQUENT-3 can be found in the full prescribing information for elotuzumab, which is available on the Empliciti website.
Bristol-Myers Squibb and AbbVie are codeveloping elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.
The who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
Elotuzumab is already approved in combination with lenalidomide and dexamethasone to treat adult myeloma patients who have received one to three prior therapies.
The FDA’s latest approval of elotuzumab is based on results from ELOQUENT-3. This phase 2 trial enrolled multiple myeloma patients who had refractory or relapsed disease and had received both lenalidomide and a proteasome inhibitor.
In the trial, patients were randomized to receive elotuzumab plus pomalidomide and dexamethasone (EPd, n = 60) or pomalidomide and dexamethasone (Pd, n = 57) in 28-day cycles until disease progression or unacceptable toxicity.
The overall response rate was 53.3% in the EPd arm and 26.3% in the Pd arm (P = .0029); the rate of complete response or stringent complete response was 8.3% and 1.8%, respectively.
Median progression-free survival was 10.25 months with EPd and 4.67 months with Pd (P = .0078).
Serious adverse events occurred in 22% of patients in the EPd arm and 15% in the Pd arm. The most frequent serious adverse events were pneumonia and respiratory tract infection.
Additional results from ELOQUENT-3 can be found in the full prescribing information for elotuzumab, which is available on the Empliciti website.
Bristol-Myers Squibb and AbbVie are codeveloping elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.
FDA approves Sympazan for Lennox-Gastaut syndrome
, according to a release from its developer. Final approval came after the orphan drug designation period for the previously marketed formulation, Onfi, came to an end in October.
LGS is a severe form of epilepsy; it can present with multiple types of seizures, as well as intellectual disabilities. Patients with LGS can have difficulty swallowing tablets or large volumes of oral suspension – which was previously the only way clobazam was delivered – because of physical limitations or behavioral or compliance issues. According to the press release from Aquestive Therapeutics, the Sympazan oral film might be able to get around those difficulties and reduce care burdens, especially with patients who are resistant to or even combative about treatment.
The approval is based on multiple pharmacokinetic studies that altogether showed that the oral film is bioequivalent to clobazam tablets and has a similar safety profile.
In a phase 3 study of 238 patients with LGS, clobazam tablets were shown to reduce drop seizures (those that involved falls) by 41% at low doses and by 68% at high doses versus a reduction of 12% seen with placebo (P less than .05 for all doses vs. placebo).
There is a risk of profound sedation when clobazam is used alongside benzodiazepines; there is also a risk of sedation and somnolence if it is used concomitantly with alcohol or other CNS depressants. Other risks associated with clobazam include suicidal ideation and behavior, serious dermatologic reactions, and physical and psychological dependence. The most common adverse reactions included constipation, pyrexia, lethargy, and drooling.
Full prescribing information can be found on the FDA website.
, according to a release from its developer. Final approval came after the orphan drug designation period for the previously marketed formulation, Onfi, came to an end in October.
LGS is a severe form of epilepsy; it can present with multiple types of seizures, as well as intellectual disabilities. Patients with LGS can have difficulty swallowing tablets or large volumes of oral suspension – which was previously the only way clobazam was delivered – because of physical limitations or behavioral or compliance issues. According to the press release from Aquestive Therapeutics, the Sympazan oral film might be able to get around those difficulties and reduce care burdens, especially with patients who are resistant to or even combative about treatment.
The approval is based on multiple pharmacokinetic studies that altogether showed that the oral film is bioequivalent to clobazam tablets and has a similar safety profile.
In a phase 3 study of 238 patients with LGS, clobazam tablets were shown to reduce drop seizures (those that involved falls) by 41% at low doses and by 68% at high doses versus a reduction of 12% seen with placebo (P less than .05 for all doses vs. placebo).
There is a risk of profound sedation when clobazam is used alongside benzodiazepines; there is also a risk of sedation and somnolence if it is used concomitantly with alcohol or other CNS depressants. Other risks associated with clobazam include suicidal ideation and behavior, serious dermatologic reactions, and physical and psychological dependence. The most common adverse reactions included constipation, pyrexia, lethargy, and drooling.
Full prescribing information can be found on the FDA website.
, according to a release from its developer. Final approval came after the orphan drug designation period for the previously marketed formulation, Onfi, came to an end in October.
LGS is a severe form of epilepsy; it can present with multiple types of seizures, as well as intellectual disabilities. Patients with LGS can have difficulty swallowing tablets or large volumes of oral suspension – which was previously the only way clobazam was delivered – because of physical limitations or behavioral or compliance issues. According to the press release from Aquestive Therapeutics, the Sympazan oral film might be able to get around those difficulties and reduce care burdens, especially with patients who are resistant to or even combative about treatment.
The approval is based on multiple pharmacokinetic studies that altogether showed that the oral film is bioequivalent to clobazam tablets and has a similar safety profile.
In a phase 3 study of 238 patients with LGS, clobazam tablets were shown to reduce drop seizures (those that involved falls) by 41% at low doses and by 68% at high doses versus a reduction of 12% seen with placebo (P less than .05 for all doses vs. placebo).
There is a risk of profound sedation when clobazam is used alongside benzodiazepines; there is also a risk of sedation and somnolence if it is used concomitantly with alcohol or other CNS depressants. Other risks associated with clobazam include suicidal ideation and behavior, serious dermatologic reactions, and physical and psychological dependence. The most common adverse reactions included constipation, pyrexia, lethargy, and drooling.
Full prescribing information can be found on the FDA website.
Sandoz halts pursuit of U.S. approval for rituximab biosimilar
.
Sandoz, a division of Novartis, was seeking Food and Drug Administration approval of GP2013 for all the same indications as the reference product – B-cell non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulgaris.
GP2013 already is approved in the European Union and elsewhere.
The FDA had accepted the biologics license application (BLA) for GP2013 in September 2017. In May 2018, the agency issued a complete response letter saying it could not approve GP2013. The agency also requested additional information to complement the BLA submission.
At the time of the complete response letter, Sandoz said it was still committed to bringing GP2013 to the U.S. market.
“We appreciate the important conversations with the FDA, which have provided specific requirements for our potential U.S. biosimilar rituximab but believe the patient and marketplace needs in the U.S. will be satisfied before we can generate the data required,” Stefan Hendriks, global head of biopharmaceuticals at Sandoz, said in a statement.
“We are disappointed to have to make this decision and stand behind the safety, efficacy, and quality of our medicine, which met the stringent criteria for approval in the European Union, Switzerland, Japan, New Zealand, and Australia.”
The BLA for GP2013 was supported, in part, by results from the ASSIST-FL trial, in which researchers compared GP2013 with the reference product (Lancet Haematol. 2017 Aug;4[8]:e350-61).
The phase 3 trial included adults with previously untreated, advanced-stage follicular lymphoma. Patients received eight cycles of cyclophosphamide, vincristine, and prednisone with either GP2013 or reference rituximab. Responders then received GP2013 or rituximab monotherapy as maintenance for up to 2 years.
At a median follow-up of 11.6 months, the overall response rate was 87% in the GP2013 arm and 88% in the rituximab arm.
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Sandoz, a division of Novartis, was seeking Food and Drug Administration approval of GP2013 for all the same indications as the reference product – B-cell non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulgaris.
GP2013 already is approved in the European Union and elsewhere.
The FDA had accepted the biologics license application (BLA) for GP2013 in September 2017. In May 2018, the agency issued a complete response letter saying it could not approve GP2013. The agency also requested additional information to complement the BLA submission.
At the time of the complete response letter, Sandoz said it was still committed to bringing GP2013 to the U.S. market.
“We appreciate the important conversations with the FDA, which have provided specific requirements for our potential U.S. biosimilar rituximab but believe the patient and marketplace needs in the U.S. will be satisfied before we can generate the data required,” Stefan Hendriks, global head of biopharmaceuticals at Sandoz, said in a statement.
“We are disappointed to have to make this decision and stand behind the safety, efficacy, and quality of our medicine, which met the stringent criteria for approval in the European Union, Switzerland, Japan, New Zealand, and Australia.”
The BLA for GP2013 was supported, in part, by results from the ASSIST-FL trial, in which researchers compared GP2013 with the reference product (Lancet Haematol. 2017 Aug;4[8]:e350-61).
The phase 3 trial included adults with previously untreated, advanced-stage follicular lymphoma. Patients received eight cycles of cyclophosphamide, vincristine, and prednisone with either GP2013 or reference rituximab. Responders then received GP2013 or rituximab monotherapy as maintenance for up to 2 years.
At a median follow-up of 11.6 months, the overall response rate was 87% in the GP2013 arm and 88% in the rituximab arm.
.
Sandoz, a division of Novartis, was seeking Food and Drug Administration approval of GP2013 for all the same indications as the reference product – B-cell non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulgaris.
GP2013 already is approved in the European Union and elsewhere.
The FDA had accepted the biologics license application (BLA) for GP2013 in September 2017. In May 2018, the agency issued a complete response letter saying it could not approve GP2013. The agency also requested additional information to complement the BLA submission.
At the time of the complete response letter, Sandoz said it was still committed to bringing GP2013 to the U.S. market.
“We appreciate the important conversations with the FDA, which have provided specific requirements for our potential U.S. biosimilar rituximab but believe the patient and marketplace needs in the U.S. will be satisfied before we can generate the data required,” Stefan Hendriks, global head of biopharmaceuticals at Sandoz, said in a statement.
“We are disappointed to have to make this decision and stand behind the safety, efficacy, and quality of our medicine, which met the stringent criteria for approval in the European Union, Switzerland, Japan, New Zealand, and Australia.”
The BLA for GP2013 was supported, in part, by results from the ASSIST-FL trial, in which researchers compared GP2013 with the reference product (Lancet Haematol. 2017 Aug;4[8]:e350-61).
The phase 3 trial included adults with previously untreated, advanced-stage follicular lymphoma. Patients received eight cycles of cyclophosphamide, vincristine, and prednisone with either GP2013 or reference rituximab. Responders then received GP2013 or rituximab monotherapy as maintenance for up to 2 years.
At a median follow-up of 11.6 months, the overall response rate was 87% in the GP2013 arm and 88% in the rituximab arm.
FDA approves lorlatinib as second line for ALK-positive advanced NSCLC
The Food and Drug Administration has granted accelerated approval to lorlatinib for patients with anaplastic lymphoma kinase (ALK)–positive metastatic non–small cell lung cancer (NSCLC) whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease or whose disease has progressed on alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease.
Approval of the next-generation ALK inhibitor was based on an overall response rate of 48% – with 4% complete and 44% partial – in a subgroup of 215 patients with ALK-positive metastatic NSCLC enrolled in a nonrandomized, phase 2 trial, the FDA said in a press announcement. All patients had been previously treated with one or more ALK kinase inhibitors.
The median response duration was 12.5 months (95% confidence interval, 8.4-23.7) and the intracranial overall response rate in 89 patients with measurable lesions in the CNS was 60% (95% CI, 49-70) with 21% complete and 38% partial responses.
Common adverse reactions in patients receiving lorlatinib were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea. The most common laboratory abnormalities were hypercholesterolemia and hypertriglyceridemia, the FDA said.
The recommended dose of lorlatinib, to be marketed as Lorbrena by Pfizer, is 100 mg orally once daily.
The Food and Drug Administration has granted accelerated approval to lorlatinib for patients with anaplastic lymphoma kinase (ALK)–positive metastatic non–small cell lung cancer (NSCLC) whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease or whose disease has progressed on alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease.
Approval of the next-generation ALK inhibitor was based on an overall response rate of 48% – with 4% complete and 44% partial – in a subgroup of 215 patients with ALK-positive metastatic NSCLC enrolled in a nonrandomized, phase 2 trial, the FDA said in a press announcement. All patients had been previously treated with one or more ALK kinase inhibitors.
The median response duration was 12.5 months (95% confidence interval, 8.4-23.7) and the intracranial overall response rate in 89 patients with measurable lesions in the CNS was 60% (95% CI, 49-70) with 21% complete and 38% partial responses.
Common adverse reactions in patients receiving lorlatinib were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea. The most common laboratory abnormalities were hypercholesterolemia and hypertriglyceridemia, the FDA said.
The recommended dose of lorlatinib, to be marketed as Lorbrena by Pfizer, is 100 mg orally once daily.
The Food and Drug Administration has granted accelerated approval to lorlatinib for patients with anaplastic lymphoma kinase (ALK)–positive metastatic non–small cell lung cancer (NSCLC) whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease or whose disease has progressed on alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease.
Approval of the next-generation ALK inhibitor was based on an overall response rate of 48% – with 4% complete and 44% partial – in a subgroup of 215 patients with ALK-positive metastatic NSCLC enrolled in a nonrandomized, phase 2 trial, the FDA said in a press announcement. All patients had been previously treated with one or more ALK kinase inhibitors.
The median response duration was 12.5 months (95% confidence interval, 8.4-23.7) and the intracranial overall response rate in 89 patients with measurable lesions in the CNS was 60% (95% CI, 49-70) with 21% complete and 38% partial responses.
Common adverse reactions in patients receiving lorlatinib were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea. The most common laboratory abnormalities were hypercholesterolemia and hypertriglyceridemia, the FDA said.
The recommended dose of lorlatinib, to be marketed as Lorbrena by Pfizer, is 100 mg orally once daily.
FDA panels back brexanolone infusion for postpartum depression
A joint panel of the Food and Drug Administration voted Nov. 2 in support of brexanolone infusion as a treatment for postpartum depression.
The 17-1 vote by members of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee was based primarily on data from three studies, including 247 women aged 18-44 years with postpartum depression; 140 received brexanolone and 107 received placebo. Effectiveness was assessed based on the Hamilton Depression Scale (HAM-D) at the end of the infusion (hour 60).
In all three studies, patients given brexanolone showed significantly improved HAM-D scores, compared with placebo. The patients experienced significant differences at hour 24, which illustrated the rapid response. “The individual item scores of the HAM-D consistently favored brexanolone IV over placebo, confirming an overall antidepressant effect of the drug,” according to the briefing document of Sage Therapeutics, developer of the drug. In addition, more than 80% of the patients in the treatment and placebo groups sustained their improvement in symptoms at 30 days after the end of the infusion.
“[Postpartum depression] is symptomatically indistinguishable from an episode of major depression,” the FDA briefing document said. “However, the timing of its onset has led to its recognition as a potentially unique illness. There are no drugs specifically approved to treat [postpartum depression].”
Some clinicians use drugs approved for major depression to treat postpartum depression, but the effectiveness of these drugs is limited, the agency said. Other interventions, such as electroconvulsive therapy, repetitive transcranial magnetic stimulation, and psychotherapy also are used, but they can take several weeks to show results.
Recent estimates of postpartum depression in the United States range from about 8% to 20%, according to the FDA document. and both the FDA and Sage Therapeutics agreed on the need for additional treatment options for women with postpartum depression. , according to Sage.
The treatment protocol for brexanolone involves a single 60-hour continuous infusion with a recommended maximum dose of 90 µg/kg/h, referred to as a “90 dose regimen.” The patient receives a single infusion per episode of postpartum depression. The infusion includes three dosing phases: titration at 30 μg/kg/h for 4 hours followed by 60 μg/kg/h for 20 hours (hour 0-24), maintenance at 90 μg/kg/h for 28 hours (hour 24-52), and taper at 60 μg/kg/h for 4 hours – followed by 30 μg/kg/h for 4 hours (hour 52-60).
Brexanolone is an allosteric modulator of GABAA receptors and “a new molecular entity not currently marketed anywhere in the world for any indication,” according to the FDA document. The drug originally was studied as a treatment for seizure patients before its antidepressant properties were discovered.
Adverse reactions observed in 3% or more of the brexanolone patients during the 60-hour treatment and 4-week follow-up included dry mouth, infusion site pain, fatigue, headache, sedation/somnolence, dizziness/vertigo, and loss of consciousness.
Of those reactions, loss of consciousness was the issue of greatest concern to the committee members and informed their discussion of the strict Risk Evaluation and Mitigation Strategy protocol that would be needed to accompany approval of the drug. The details of the REMS will be determined, but the basics of the FDA’s proposed REMS to mitigate the risk of loss of consciousness include administration of the drug only in medically supervised settings by an authorized representative.
In addition, the proposed REMS states that the authorized representative must “establish policies and procedures to ensure that 1) all staff are trained on the risks and 2) the product is not dispensed for use outside the health care setting.”
The proposed REMS also stated that, “Patients must be continuously monitored for the duration of the infusion and 12 hours after, by health care provider who can intervene if the patient experiences excessive sedation or loss of consciousness.”
Despite those concerns, which most committee members thought could be addressed by the REMS, the overall impression of the committees’ members was that brexanolone could have a significant impact on postpartum depression. According to one member, brexanolone is mechanistically “groundbreaking” and “could be a tremendous help in changing the trajectory of postpartum depression.”
The FDA usually follows its panels’ recommendations, which are not binding.
A joint panel of the Food and Drug Administration voted Nov. 2 in support of brexanolone infusion as a treatment for postpartum depression.
The 17-1 vote by members of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee was based primarily on data from three studies, including 247 women aged 18-44 years with postpartum depression; 140 received brexanolone and 107 received placebo. Effectiveness was assessed based on the Hamilton Depression Scale (HAM-D) at the end of the infusion (hour 60).
In all three studies, patients given brexanolone showed significantly improved HAM-D scores, compared with placebo. The patients experienced significant differences at hour 24, which illustrated the rapid response. “The individual item scores of the HAM-D consistently favored brexanolone IV over placebo, confirming an overall antidepressant effect of the drug,” according to the briefing document of Sage Therapeutics, developer of the drug. In addition, more than 80% of the patients in the treatment and placebo groups sustained their improvement in symptoms at 30 days after the end of the infusion.
“[Postpartum depression] is symptomatically indistinguishable from an episode of major depression,” the FDA briefing document said. “However, the timing of its onset has led to its recognition as a potentially unique illness. There are no drugs specifically approved to treat [postpartum depression].”
Some clinicians use drugs approved for major depression to treat postpartum depression, but the effectiveness of these drugs is limited, the agency said. Other interventions, such as electroconvulsive therapy, repetitive transcranial magnetic stimulation, and psychotherapy also are used, but they can take several weeks to show results.
Recent estimates of postpartum depression in the United States range from about 8% to 20%, according to the FDA document. and both the FDA and Sage Therapeutics agreed on the need for additional treatment options for women with postpartum depression. , according to Sage.
The treatment protocol for brexanolone involves a single 60-hour continuous infusion with a recommended maximum dose of 90 µg/kg/h, referred to as a “90 dose regimen.” The patient receives a single infusion per episode of postpartum depression. The infusion includes three dosing phases: titration at 30 μg/kg/h for 4 hours followed by 60 μg/kg/h for 20 hours (hour 0-24), maintenance at 90 μg/kg/h for 28 hours (hour 24-52), and taper at 60 μg/kg/h for 4 hours – followed by 30 μg/kg/h for 4 hours (hour 52-60).
Brexanolone is an allosteric modulator of GABAA receptors and “a new molecular entity not currently marketed anywhere in the world for any indication,” according to the FDA document. The drug originally was studied as a treatment for seizure patients before its antidepressant properties were discovered.
Adverse reactions observed in 3% or more of the brexanolone patients during the 60-hour treatment and 4-week follow-up included dry mouth, infusion site pain, fatigue, headache, sedation/somnolence, dizziness/vertigo, and loss of consciousness.
Of those reactions, loss of consciousness was the issue of greatest concern to the committee members and informed their discussion of the strict Risk Evaluation and Mitigation Strategy protocol that would be needed to accompany approval of the drug. The details of the REMS will be determined, but the basics of the FDA’s proposed REMS to mitigate the risk of loss of consciousness include administration of the drug only in medically supervised settings by an authorized representative.
In addition, the proposed REMS states that the authorized representative must “establish policies and procedures to ensure that 1) all staff are trained on the risks and 2) the product is not dispensed for use outside the health care setting.”
The proposed REMS also stated that, “Patients must be continuously monitored for the duration of the infusion and 12 hours after, by health care provider who can intervene if the patient experiences excessive sedation or loss of consciousness.”
Despite those concerns, which most committee members thought could be addressed by the REMS, the overall impression of the committees’ members was that brexanolone could have a significant impact on postpartum depression. According to one member, brexanolone is mechanistically “groundbreaking” and “could be a tremendous help in changing the trajectory of postpartum depression.”
The FDA usually follows its panels’ recommendations, which are not binding.
A joint panel of the Food and Drug Administration voted Nov. 2 in support of brexanolone infusion as a treatment for postpartum depression.
The 17-1 vote by members of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee was based primarily on data from three studies, including 247 women aged 18-44 years with postpartum depression; 140 received brexanolone and 107 received placebo. Effectiveness was assessed based on the Hamilton Depression Scale (HAM-D) at the end of the infusion (hour 60).
In all three studies, patients given brexanolone showed significantly improved HAM-D scores, compared with placebo. The patients experienced significant differences at hour 24, which illustrated the rapid response. “The individual item scores of the HAM-D consistently favored brexanolone IV over placebo, confirming an overall antidepressant effect of the drug,” according to the briefing document of Sage Therapeutics, developer of the drug. In addition, more than 80% of the patients in the treatment and placebo groups sustained their improvement in symptoms at 30 days after the end of the infusion.
“[Postpartum depression] is symptomatically indistinguishable from an episode of major depression,” the FDA briefing document said. “However, the timing of its onset has led to its recognition as a potentially unique illness. There are no drugs specifically approved to treat [postpartum depression].”
Some clinicians use drugs approved for major depression to treat postpartum depression, but the effectiveness of these drugs is limited, the agency said. Other interventions, such as electroconvulsive therapy, repetitive transcranial magnetic stimulation, and psychotherapy also are used, but they can take several weeks to show results.
Recent estimates of postpartum depression in the United States range from about 8% to 20%, according to the FDA document. and both the FDA and Sage Therapeutics agreed on the need for additional treatment options for women with postpartum depression. , according to Sage.
The treatment protocol for brexanolone involves a single 60-hour continuous infusion with a recommended maximum dose of 90 µg/kg/h, referred to as a “90 dose regimen.” The patient receives a single infusion per episode of postpartum depression. The infusion includes three dosing phases: titration at 30 μg/kg/h for 4 hours followed by 60 μg/kg/h for 20 hours (hour 0-24), maintenance at 90 μg/kg/h for 28 hours (hour 24-52), and taper at 60 μg/kg/h for 4 hours – followed by 30 μg/kg/h for 4 hours (hour 52-60).
Brexanolone is an allosteric modulator of GABAA receptors and “a new molecular entity not currently marketed anywhere in the world for any indication,” according to the FDA document. The drug originally was studied as a treatment for seizure patients before its antidepressant properties were discovered.
Adverse reactions observed in 3% or more of the brexanolone patients during the 60-hour treatment and 4-week follow-up included dry mouth, infusion site pain, fatigue, headache, sedation/somnolence, dizziness/vertigo, and loss of consciousness.
Of those reactions, loss of consciousness was the issue of greatest concern to the committee members and informed their discussion of the strict Risk Evaluation and Mitigation Strategy protocol that would be needed to accompany approval of the drug. The details of the REMS will be determined, but the basics of the FDA’s proposed REMS to mitigate the risk of loss of consciousness include administration of the drug only in medically supervised settings by an authorized representative.
In addition, the proposed REMS states that the authorized representative must “establish policies and procedures to ensure that 1) all staff are trained on the risks and 2) the product is not dispensed for use outside the health care setting.”
The proposed REMS also stated that, “Patients must be continuously monitored for the duration of the infusion and 12 hours after, by health care provider who can intervene if the patient experiences excessive sedation or loss of consciousness.”
Despite those concerns, which most committee members thought could be addressed by the REMS, the overall impression of the committees’ members was that brexanolone could have a significant impact on postpartum depression. According to one member, brexanolone is mechanistically “groundbreaking” and “could be a tremendous help in changing the trajectory of postpartum depression.”
The FDA usually follows its panels’ recommendations, which are not binding.
