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FDA clears new biomarker assays for early Alzheimer’s detection
The Elecsys beta-amyloid (1-42) CSF II (Abeta42) and Elecsys total-tau CSF assays (tTau) (used as a tTau/Abeta42 ratio) are for use in adults ages 55 and older being evaluated for AD.
They join the Elecsys beta-amyloid (1-42) CSF II (Abeta42) and Elecsys phospho-tau (181P) CSF (pTau181) assays (used as a pTau181/Abeta42 ratio) that received FDA 510(k) clearance in 2022.
“An early and accurate diagnosis can help patients, caregivers and physicians determine a path forward, and the Elecsys CSF assays support diagnosis at early disease stages, when treatment is most effective,” Brad Moore, president and CEO of Roche Diagnostics North America, said in a statement.
Appropriate use recommendations for new and emerging AD drugs call for confirmation of amyloid pathology. Currently, the only FDA-cleared methods to confirm amyloid pathology are CSF tests and PET scans.
“The Elecsys AD CSF assays are concordant with amyloid PET scan imaging and have the potential to provide a more affordable and accessible routine option to confirm the presence of amyloid pathology in the brain,” Roche said.
“They also offer detection of both amyloid and tau biomarkers from one draw, with no radiation and potential to detect Alzheimer’s pathology in early stages of disease,” the company added.
The previously approved Elecsys pTau181/Abeta42 ratio is currently available and the newly approved Elecsys tTau/Abeta42 ratio will be available in the fourth quarter of 2023.
A version of this article first appeared on Medscape.com.
The Elecsys beta-amyloid (1-42) CSF II (Abeta42) and Elecsys total-tau CSF assays (tTau) (used as a tTau/Abeta42 ratio) are for use in adults ages 55 and older being evaluated for AD.
They join the Elecsys beta-amyloid (1-42) CSF II (Abeta42) and Elecsys phospho-tau (181P) CSF (pTau181) assays (used as a pTau181/Abeta42 ratio) that received FDA 510(k) clearance in 2022.
“An early and accurate diagnosis can help patients, caregivers and physicians determine a path forward, and the Elecsys CSF assays support diagnosis at early disease stages, when treatment is most effective,” Brad Moore, president and CEO of Roche Diagnostics North America, said in a statement.
Appropriate use recommendations for new and emerging AD drugs call for confirmation of amyloid pathology. Currently, the only FDA-cleared methods to confirm amyloid pathology are CSF tests and PET scans.
“The Elecsys AD CSF assays are concordant with amyloid PET scan imaging and have the potential to provide a more affordable and accessible routine option to confirm the presence of amyloid pathology in the brain,” Roche said.
“They also offer detection of both amyloid and tau biomarkers from one draw, with no radiation and potential to detect Alzheimer’s pathology in early stages of disease,” the company added.
The previously approved Elecsys pTau181/Abeta42 ratio is currently available and the newly approved Elecsys tTau/Abeta42 ratio will be available in the fourth quarter of 2023.
A version of this article first appeared on Medscape.com.
The Elecsys beta-amyloid (1-42) CSF II (Abeta42) and Elecsys total-tau CSF assays (tTau) (used as a tTau/Abeta42 ratio) are for use in adults ages 55 and older being evaluated for AD.
They join the Elecsys beta-amyloid (1-42) CSF II (Abeta42) and Elecsys phospho-tau (181P) CSF (pTau181) assays (used as a pTau181/Abeta42 ratio) that received FDA 510(k) clearance in 2022.
“An early and accurate diagnosis can help patients, caregivers and physicians determine a path forward, and the Elecsys CSF assays support diagnosis at early disease stages, when treatment is most effective,” Brad Moore, president and CEO of Roche Diagnostics North America, said in a statement.
Appropriate use recommendations for new and emerging AD drugs call for confirmation of amyloid pathology. Currently, the only FDA-cleared methods to confirm amyloid pathology are CSF tests and PET scans.
“The Elecsys AD CSF assays are concordant with amyloid PET scan imaging and have the potential to provide a more affordable and accessible routine option to confirm the presence of amyloid pathology in the brain,” Roche said.
“They also offer detection of both amyloid and tau biomarkers from one draw, with no radiation and potential to detect Alzheimer’s pathology in early stages of disease,” the company added.
The previously approved Elecsys pTau181/Abeta42 ratio is currently available and the newly approved Elecsys tTau/Abeta42 ratio will be available in the fourth quarter of 2023.
A version of this article first appeared on Medscape.com.
FDA approves talazoparib for metastatic prostate cancer
Talazoparib is already approved for adults with deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer. The new approval, granted following priority review, is based on findings from the randomized, placebo-controlled, phase 3 TALAPRO-2 trial, published in The Lancet.
The 399 patients in the study were randomly assigned in a 1:1 ratio to receive either enzalutamide 160 mg daily plus either talazoparib 0.5 mg or placebo daily. Median radiographic progression-free survival (PFS) was not reached in the treatment group; it was 13.8 months in the placebo group (hazard ratio, 0.45). In an exploratory analysis by BRCA mutation status, patients with BRCA-mutated disease who received talazoparib exhibited an even stronger median radiographic PFS (HR, 0.20; not reached vs. 11 months) in comparison with those without BRCA-mutated disease (HR, 0.72; 24.7 vs. 16.7 months).
Serious adverse reactions occurred in 30% of patients who received talazoparib plus enzalutamide. The most common serious adverse reactions, reported in more than 2% of patients, included anemia (9%) and fracture (3%). Discontinuation of talazoparib occurred in 10% of patients, according to a Pfizer statement.
Pfizer also noted that a marketing authorization application for the drug combination has been accepted for review by the European Medicines Agency.
“Despite treatment advancement in metastatic castration-resistant prostate cancer, the disease can progress quickly, and many patients may only receive one line of therapy,” lead investigator Neeraj Agarwal, MD, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, said in a statement. Patients with metastatic castration-resistant prostate cancer harboring HRR genetic alterations have even worse outcomes, and thus the FDA’s approval of the talazoparib and enzalutamide combination “represents a treatment option deserving of excitement and attention.”
A version of this article originally appeared on Medscape.com.
Talazoparib is already approved for adults with deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer. The new approval, granted following priority review, is based on findings from the randomized, placebo-controlled, phase 3 TALAPRO-2 trial, published in The Lancet.
The 399 patients in the study were randomly assigned in a 1:1 ratio to receive either enzalutamide 160 mg daily plus either talazoparib 0.5 mg or placebo daily. Median radiographic progression-free survival (PFS) was not reached in the treatment group; it was 13.8 months in the placebo group (hazard ratio, 0.45). In an exploratory analysis by BRCA mutation status, patients with BRCA-mutated disease who received talazoparib exhibited an even stronger median radiographic PFS (HR, 0.20; not reached vs. 11 months) in comparison with those without BRCA-mutated disease (HR, 0.72; 24.7 vs. 16.7 months).
Serious adverse reactions occurred in 30% of patients who received talazoparib plus enzalutamide. The most common serious adverse reactions, reported in more than 2% of patients, included anemia (9%) and fracture (3%). Discontinuation of talazoparib occurred in 10% of patients, according to a Pfizer statement.
Pfizer also noted that a marketing authorization application for the drug combination has been accepted for review by the European Medicines Agency.
“Despite treatment advancement in metastatic castration-resistant prostate cancer, the disease can progress quickly, and many patients may only receive one line of therapy,” lead investigator Neeraj Agarwal, MD, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, said in a statement. Patients with metastatic castration-resistant prostate cancer harboring HRR genetic alterations have even worse outcomes, and thus the FDA’s approval of the talazoparib and enzalutamide combination “represents a treatment option deserving of excitement and attention.”
A version of this article originally appeared on Medscape.com.
Talazoparib is already approved for adults with deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer. The new approval, granted following priority review, is based on findings from the randomized, placebo-controlled, phase 3 TALAPRO-2 trial, published in The Lancet.
The 399 patients in the study were randomly assigned in a 1:1 ratio to receive either enzalutamide 160 mg daily plus either talazoparib 0.5 mg or placebo daily. Median radiographic progression-free survival (PFS) was not reached in the treatment group; it was 13.8 months in the placebo group (hazard ratio, 0.45). In an exploratory analysis by BRCA mutation status, patients with BRCA-mutated disease who received talazoparib exhibited an even stronger median radiographic PFS (HR, 0.20; not reached vs. 11 months) in comparison with those without BRCA-mutated disease (HR, 0.72; 24.7 vs. 16.7 months).
Serious adverse reactions occurred in 30% of patients who received talazoparib plus enzalutamide. The most common serious adverse reactions, reported in more than 2% of patients, included anemia (9%) and fracture (3%). Discontinuation of talazoparib occurred in 10% of patients, according to a Pfizer statement.
Pfizer also noted that a marketing authorization application for the drug combination has been accepted for review by the European Medicines Agency.
“Despite treatment advancement in metastatic castration-resistant prostate cancer, the disease can progress quickly, and many patients may only receive one line of therapy,” lead investigator Neeraj Agarwal, MD, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, said in a statement. Patients with metastatic castration-resistant prostate cancer harboring HRR genetic alterations have even worse outcomes, and thus the FDA’s approval of the talazoparib and enzalutamide combination “represents a treatment option deserving of excitement and attention.”
A version of this article originally appeared on Medscape.com.
FDA approves glofitamab for DLBCL
The indication is for use in adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified or with LBCL arising from follicular lymphoma who have received two or more lines of systemic therapy.
The product is a T cell–engaging bispecific antibody developed by Genentech, which has a similar product, mosunetuzumab-axgb (Lunsumio), for the treatment of follicular lymphoma. Lunsumio was approved in December 2022.
These drugs could be considered a first choice in the setting of third-line therapy, suggests an expert writing recently in The New England Journal of Medicine.
Nancy Bartlett, MD, from the Siteman Cancer Center, Washington University in St. Louis, is the author of an editorial that accompanied the publication of results with glofitamab in the pivotal trial that led to its approval.
“Bispecific agents will be an excellent option for the 60% of patients in whom second-line CAR [chimeric antigen receptor] T-cell therapy fails,” she wrote in her editorial.
Dr. Bartlett suggests that these agents may be preferred over CAR T cells. “If longer follow-up confirms that the majority of complete remissions with bispecific agents are durable, on the basis of the advantages of availability (including in the community setting) and more favorable immediate and late toxic-effect profiles, bispecific agents could be considered as the initial choice. ... CAR T-cell therapy could be held in reserve for patients who do not have a complete response or who have a relapse after a complete response.”
Most common form of non-Hodgkin’s lymphoma
DLBCL is the most common form of non-Hodgkin’s lymphoma in the United States, the company noted in a press release. While many people with DLBCL are responsive to treatment, the majority of those who experience relapse or whose condition is refractory to subsequent treatments have poor outcomes.
“Patients with relapsed or refractory diffuse large B-cell lymphoma may experience rapid progression of their cancer and often urgently need an effective treatment option that can be administered without delay,” commented Krish Patel, MD, director of the lymphoma program at the Swedish Cancer Institute in Seattle, who is an investigator on the clinical trial that led to the product’s approval. He said that the results from trials suggest that glofitamab gives patients “a chance for complete remission with a fixed-duration immunotherapy and that such remissions can potentially be sustained after the end of their treatment.”
The accelerated approval is based on response rate and durability of response results from the phase 1/2 NP30179 study.
Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
This trial involved 132 patients with DLBCL who experienced relapse or whose condition was refractory to prior therapies. About one-third of patients (30%) had received prior CAR T-cell therapy. Additionally, for 83% of patients, the condition was refractory to their most recent therapy.
Glofitamab was given to all patients as a fixed course for 8.5 months.
More than half (56%) achieved an overall response, and 43% achieved a complete response. Over two-thirds (68.5%) of those who responded continued to respond for at least 9 months The median duration of response was 1.5 years.
The most common adverse events were cytokine release syndrome (CRS; 70%), which may be serious or life-threatening; musculoskeletal pain (21%); fatigue (20%); and rash (20%). CRS was generally of low grade (52% of patients experienced grade 1 CRS, and 14% experienced grade 2).
Results from the NP30179 trial were published in December 2022.
The complete response rates seen with glofitamab rivals the durable complete response that has been observed with CAR T-cell therapy, Dr. Bartlett noted in the accompanying editorial. “Although these results are promising, it is still too early to estimate the curative potential of glofitamab.”
The indication is for use in adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified or with LBCL arising from follicular lymphoma who have received two or more lines of systemic therapy.
The product is a T cell–engaging bispecific antibody developed by Genentech, which has a similar product, mosunetuzumab-axgb (Lunsumio), for the treatment of follicular lymphoma. Lunsumio was approved in December 2022.
These drugs could be considered a first choice in the setting of third-line therapy, suggests an expert writing recently in The New England Journal of Medicine.
Nancy Bartlett, MD, from the Siteman Cancer Center, Washington University in St. Louis, is the author of an editorial that accompanied the publication of results with glofitamab in the pivotal trial that led to its approval.
“Bispecific agents will be an excellent option for the 60% of patients in whom second-line CAR [chimeric antigen receptor] T-cell therapy fails,” she wrote in her editorial.
Dr. Bartlett suggests that these agents may be preferred over CAR T cells. “If longer follow-up confirms that the majority of complete remissions with bispecific agents are durable, on the basis of the advantages of availability (including in the community setting) and more favorable immediate and late toxic-effect profiles, bispecific agents could be considered as the initial choice. ... CAR T-cell therapy could be held in reserve for patients who do not have a complete response or who have a relapse after a complete response.”
Most common form of non-Hodgkin’s lymphoma
DLBCL is the most common form of non-Hodgkin’s lymphoma in the United States, the company noted in a press release. While many people with DLBCL are responsive to treatment, the majority of those who experience relapse or whose condition is refractory to subsequent treatments have poor outcomes.
“Patients with relapsed or refractory diffuse large B-cell lymphoma may experience rapid progression of their cancer and often urgently need an effective treatment option that can be administered without delay,” commented Krish Patel, MD, director of the lymphoma program at the Swedish Cancer Institute in Seattle, who is an investigator on the clinical trial that led to the product’s approval. He said that the results from trials suggest that glofitamab gives patients “a chance for complete remission with a fixed-duration immunotherapy and that such remissions can potentially be sustained after the end of their treatment.”
The accelerated approval is based on response rate and durability of response results from the phase 1/2 NP30179 study.
Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
This trial involved 132 patients with DLBCL who experienced relapse or whose condition was refractory to prior therapies. About one-third of patients (30%) had received prior CAR T-cell therapy. Additionally, for 83% of patients, the condition was refractory to their most recent therapy.
Glofitamab was given to all patients as a fixed course for 8.5 months.
More than half (56%) achieved an overall response, and 43% achieved a complete response. Over two-thirds (68.5%) of those who responded continued to respond for at least 9 months The median duration of response was 1.5 years.
The most common adverse events were cytokine release syndrome (CRS; 70%), which may be serious or life-threatening; musculoskeletal pain (21%); fatigue (20%); and rash (20%). CRS was generally of low grade (52% of patients experienced grade 1 CRS, and 14% experienced grade 2).
Results from the NP30179 trial were published in December 2022.
The complete response rates seen with glofitamab rivals the durable complete response that has been observed with CAR T-cell therapy, Dr. Bartlett noted in the accompanying editorial. “Although these results are promising, it is still too early to estimate the curative potential of glofitamab.”
The indication is for use in adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified or with LBCL arising from follicular lymphoma who have received two or more lines of systemic therapy.
The product is a T cell–engaging bispecific antibody developed by Genentech, which has a similar product, mosunetuzumab-axgb (Lunsumio), for the treatment of follicular lymphoma. Lunsumio was approved in December 2022.
These drugs could be considered a first choice in the setting of third-line therapy, suggests an expert writing recently in The New England Journal of Medicine.
Nancy Bartlett, MD, from the Siteman Cancer Center, Washington University in St. Louis, is the author of an editorial that accompanied the publication of results with glofitamab in the pivotal trial that led to its approval.
“Bispecific agents will be an excellent option for the 60% of patients in whom second-line CAR [chimeric antigen receptor] T-cell therapy fails,” she wrote in her editorial.
Dr. Bartlett suggests that these agents may be preferred over CAR T cells. “If longer follow-up confirms that the majority of complete remissions with bispecific agents are durable, on the basis of the advantages of availability (including in the community setting) and more favorable immediate and late toxic-effect profiles, bispecific agents could be considered as the initial choice. ... CAR T-cell therapy could be held in reserve for patients who do not have a complete response or who have a relapse after a complete response.”
Most common form of non-Hodgkin’s lymphoma
DLBCL is the most common form of non-Hodgkin’s lymphoma in the United States, the company noted in a press release. While many people with DLBCL are responsive to treatment, the majority of those who experience relapse or whose condition is refractory to subsequent treatments have poor outcomes.
“Patients with relapsed or refractory diffuse large B-cell lymphoma may experience rapid progression of their cancer and often urgently need an effective treatment option that can be administered without delay,” commented Krish Patel, MD, director of the lymphoma program at the Swedish Cancer Institute in Seattle, who is an investigator on the clinical trial that led to the product’s approval. He said that the results from trials suggest that glofitamab gives patients “a chance for complete remission with a fixed-duration immunotherapy and that such remissions can potentially be sustained after the end of their treatment.”
The accelerated approval is based on response rate and durability of response results from the phase 1/2 NP30179 study.
Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
This trial involved 132 patients with DLBCL who experienced relapse or whose condition was refractory to prior therapies. About one-third of patients (30%) had received prior CAR T-cell therapy. Additionally, for 83% of patients, the condition was refractory to their most recent therapy.
Glofitamab was given to all patients as a fixed course for 8.5 months.
More than half (56%) achieved an overall response, and 43% achieved a complete response. Over two-thirds (68.5%) of those who responded continued to respond for at least 9 months The median duration of response was 1.5 years.
The most common adverse events were cytokine release syndrome (CRS; 70%), which may be serious or life-threatening; musculoskeletal pain (21%); fatigue (20%); and rash (20%). CRS was generally of low grade (52% of patients experienced grade 1 CRS, and 14% experienced grade 2).
Results from the NP30179 trial were published in December 2022.
The complete response rates seen with glofitamab rivals the durable complete response that has been observed with CAR T-cell therapy, Dr. Bartlett noted in the accompanying editorial. “Although these results are promising, it is still too early to estimate the curative potential of glofitamab.”
FDA panel unanimously endorses lecanemab for Alzheimer’s
“Overall, the study demonstrated clearly that this is an effective treatment,” said acting chair Robert C. Alexander, MD, chief scientific officer, Alzheimer’s Prevention Initiative, Banner Alzheimer’s Institute, and research professor, department of psychiatry, University of Arizona, Phoenix, during the meeting.
An intravenous infusion targeting amyloid-beta, lecanemab received accelerated FDA approved earlier in 2023 for the treatment of early Alzheimer’s disease (AD). The company was required to complete a confirmatory study to verify and describe the product’s clinical benefit.
The Peripheral and Central Nervous System Drugs Advisory Committee met to discuss this phase 3 study (CLARITY-AD). The multicenter, double-blind study included 1,795 patients (mean age, 71 years) who had mild cognitive impairment caused by AD or mild AD dementia.
Delayed progression
Study participants had a broad range of comorbidities, and many were concomitantly receiving other medications. Black people were underrepresented in the study at just 3% of the total cohort.
Patients were randomly assigned to receive placebo or lecanemab 10 mg/kg biweekly. In addition to a placebo-controlled period and safety follow-up, the study has an ongoing extension phase of up to 4 years.
The study met its primary endpoint, showing a highly statistically significant 27% less decline on the Clinical Dementia Rating-Sum of Boxes at 18 months (difference in adjusted mean, –0.45; 95% CI, –0.67 to –0.23; P = .00005).
This was supported by a significant 26% difference on the AD Assessment Scale–Cognitive Subscale with 14 tasks (ADAS-Cog 14).
The drug also affected function, with a 37% decrease, compared with placebo, on the AD Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment.
Committee members heard that the results signal delays in disease progression by about 5 months, giving patients more time to live independently and participate in hobbies and interests.
Patients who received the active drug also experienced quality of life benefits. Compared with patients who received placebo, those who took lecanemab had 49% less decline as measured with the European Quality of Life–5 Dimensions scale and 56% less decline as measured by the Quality of Life in AD scale, and caregivers reported less burden.
Lecanemab also affected biomarkers of amyloid, tau, and neurodegeneration, providing a biological basis for the treatment effects consistent with slowing of disease progression.
Unanimous support
All six committee members agreed by vote that the study provides evidence of clinical benefit. They variously descried the study and results as “robust,” “compelling,” “well conducted,” “clear and consistent,” and “clinically meaningful.”
In the active treatment group, there was a higher incidence of amyloid-related imaging abnormalities (ARIAs), which can be serious and life-threatening but are usually asymptomatic. In this study, most ARIAs had resolved by 3 months.
Deaths occurred in 0.8% of the placebo and 0.7% of the treatment group. Dean Follmann, PhD, assistant director for biostatistics, National Institute of Allergy and Infectious Diseases, Bethesda, Md., noted that the numbers of deaths and serious adverse events were “quite similar” in the two groups.
“And for serious ARIA, there was an imbalance favoring placebo, but overall, these were pretty rare,” he said.
Subgroup concerns
Committee members discussed the risk/benefit profile for three subgroups of patients – those with apolipoprotein E4 (apo E4) allele, patients taking an anticoagulant, and those with cerebral amyloid angiopathy (CAA).
In the apo E4 group, the study’s primary endpoint did not favor the drug, but secondary endpoints did.
“I think the general feeling [for apo E4 status] is that the risk/benefit still remains favorable, especially when looking across multiple endpoints,” said Dr. Alexander.
However, some members supported recommending genetic testing before initiating the drug.
The views were more diverse for the use of lecanemab in the presence of an anticoagulant, which may increase the risk for cerebral hemorrhage. Some committee members strongly recommended that these patients not receive lecanemab, while others highlighted the need for more information, owing to uncertainties about the risks.
With respect to CAA, most members supported the idea of considering use of the drug in the presence of this condition, but only after discussing the risks with patients and their families and in the presence of a robust reporting system.
An Alzheimer’s Association representative was in attendance during the public hearing portion of the meeting to express support for traditional approval of lecanemab for people with early AD.
The association strongly favors full Medicare coverage for FDA-approved AD treatments. The Centers for Medicare & Medicaid Services has determined that AD treatments receiving traditional FDA approval will be covered if clinicians register and enter data in a registry.
“While this is an important signal that CMS wants to improve access to FDA-approved treatments, registry as a condition of coverage is an unnecessary and potentially harmful barrier,” said the Alzheimer’s Association in a press release following the meeting.
A version of this article first appeared on Medscape.com.
“Overall, the study demonstrated clearly that this is an effective treatment,” said acting chair Robert C. Alexander, MD, chief scientific officer, Alzheimer’s Prevention Initiative, Banner Alzheimer’s Institute, and research professor, department of psychiatry, University of Arizona, Phoenix, during the meeting.
An intravenous infusion targeting amyloid-beta, lecanemab received accelerated FDA approved earlier in 2023 for the treatment of early Alzheimer’s disease (AD). The company was required to complete a confirmatory study to verify and describe the product’s clinical benefit.
The Peripheral and Central Nervous System Drugs Advisory Committee met to discuss this phase 3 study (CLARITY-AD). The multicenter, double-blind study included 1,795 patients (mean age, 71 years) who had mild cognitive impairment caused by AD or mild AD dementia.
Delayed progression
Study participants had a broad range of comorbidities, and many were concomitantly receiving other medications. Black people were underrepresented in the study at just 3% of the total cohort.
Patients were randomly assigned to receive placebo or lecanemab 10 mg/kg biweekly. In addition to a placebo-controlled period and safety follow-up, the study has an ongoing extension phase of up to 4 years.
The study met its primary endpoint, showing a highly statistically significant 27% less decline on the Clinical Dementia Rating-Sum of Boxes at 18 months (difference in adjusted mean, –0.45; 95% CI, –0.67 to –0.23; P = .00005).
This was supported by a significant 26% difference on the AD Assessment Scale–Cognitive Subscale with 14 tasks (ADAS-Cog 14).
The drug also affected function, with a 37% decrease, compared with placebo, on the AD Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment.
Committee members heard that the results signal delays in disease progression by about 5 months, giving patients more time to live independently and participate in hobbies and interests.
Patients who received the active drug also experienced quality of life benefits. Compared with patients who received placebo, those who took lecanemab had 49% less decline as measured with the European Quality of Life–5 Dimensions scale and 56% less decline as measured by the Quality of Life in AD scale, and caregivers reported less burden.
Lecanemab also affected biomarkers of amyloid, tau, and neurodegeneration, providing a biological basis for the treatment effects consistent with slowing of disease progression.
Unanimous support
All six committee members agreed by vote that the study provides evidence of clinical benefit. They variously descried the study and results as “robust,” “compelling,” “well conducted,” “clear and consistent,” and “clinically meaningful.”
In the active treatment group, there was a higher incidence of amyloid-related imaging abnormalities (ARIAs), which can be serious and life-threatening but are usually asymptomatic. In this study, most ARIAs had resolved by 3 months.
Deaths occurred in 0.8% of the placebo and 0.7% of the treatment group. Dean Follmann, PhD, assistant director for biostatistics, National Institute of Allergy and Infectious Diseases, Bethesda, Md., noted that the numbers of deaths and serious adverse events were “quite similar” in the two groups.
“And for serious ARIA, there was an imbalance favoring placebo, but overall, these were pretty rare,” he said.
Subgroup concerns
Committee members discussed the risk/benefit profile for three subgroups of patients – those with apolipoprotein E4 (apo E4) allele, patients taking an anticoagulant, and those with cerebral amyloid angiopathy (CAA).
In the apo E4 group, the study’s primary endpoint did not favor the drug, but secondary endpoints did.
“I think the general feeling [for apo E4 status] is that the risk/benefit still remains favorable, especially when looking across multiple endpoints,” said Dr. Alexander.
However, some members supported recommending genetic testing before initiating the drug.
The views were more diverse for the use of lecanemab in the presence of an anticoagulant, which may increase the risk for cerebral hemorrhage. Some committee members strongly recommended that these patients not receive lecanemab, while others highlighted the need for more information, owing to uncertainties about the risks.
With respect to CAA, most members supported the idea of considering use of the drug in the presence of this condition, but only after discussing the risks with patients and their families and in the presence of a robust reporting system.
An Alzheimer’s Association representative was in attendance during the public hearing portion of the meeting to express support for traditional approval of lecanemab for people with early AD.
The association strongly favors full Medicare coverage for FDA-approved AD treatments. The Centers for Medicare & Medicaid Services has determined that AD treatments receiving traditional FDA approval will be covered if clinicians register and enter data in a registry.
“While this is an important signal that CMS wants to improve access to FDA-approved treatments, registry as a condition of coverage is an unnecessary and potentially harmful barrier,” said the Alzheimer’s Association in a press release following the meeting.
A version of this article first appeared on Medscape.com.
“Overall, the study demonstrated clearly that this is an effective treatment,” said acting chair Robert C. Alexander, MD, chief scientific officer, Alzheimer’s Prevention Initiative, Banner Alzheimer’s Institute, and research professor, department of psychiatry, University of Arizona, Phoenix, during the meeting.
An intravenous infusion targeting amyloid-beta, lecanemab received accelerated FDA approved earlier in 2023 for the treatment of early Alzheimer’s disease (AD). The company was required to complete a confirmatory study to verify and describe the product’s clinical benefit.
The Peripheral and Central Nervous System Drugs Advisory Committee met to discuss this phase 3 study (CLARITY-AD). The multicenter, double-blind study included 1,795 patients (mean age, 71 years) who had mild cognitive impairment caused by AD or mild AD dementia.
Delayed progression
Study participants had a broad range of comorbidities, and many were concomitantly receiving other medications. Black people were underrepresented in the study at just 3% of the total cohort.
Patients were randomly assigned to receive placebo or lecanemab 10 mg/kg biweekly. In addition to a placebo-controlled period and safety follow-up, the study has an ongoing extension phase of up to 4 years.
The study met its primary endpoint, showing a highly statistically significant 27% less decline on the Clinical Dementia Rating-Sum of Boxes at 18 months (difference in adjusted mean, –0.45; 95% CI, –0.67 to –0.23; P = .00005).
This was supported by a significant 26% difference on the AD Assessment Scale–Cognitive Subscale with 14 tasks (ADAS-Cog 14).
The drug also affected function, with a 37% decrease, compared with placebo, on the AD Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment.
Committee members heard that the results signal delays in disease progression by about 5 months, giving patients more time to live independently and participate in hobbies and interests.
Patients who received the active drug also experienced quality of life benefits. Compared with patients who received placebo, those who took lecanemab had 49% less decline as measured with the European Quality of Life–5 Dimensions scale and 56% less decline as measured by the Quality of Life in AD scale, and caregivers reported less burden.
Lecanemab also affected biomarkers of amyloid, tau, and neurodegeneration, providing a biological basis for the treatment effects consistent with slowing of disease progression.
Unanimous support
All six committee members agreed by vote that the study provides evidence of clinical benefit. They variously descried the study and results as “robust,” “compelling,” “well conducted,” “clear and consistent,” and “clinically meaningful.”
In the active treatment group, there was a higher incidence of amyloid-related imaging abnormalities (ARIAs), which can be serious and life-threatening but are usually asymptomatic. In this study, most ARIAs had resolved by 3 months.
Deaths occurred in 0.8% of the placebo and 0.7% of the treatment group. Dean Follmann, PhD, assistant director for biostatistics, National Institute of Allergy and Infectious Diseases, Bethesda, Md., noted that the numbers of deaths and serious adverse events were “quite similar” in the two groups.
“And for serious ARIA, there was an imbalance favoring placebo, but overall, these were pretty rare,” he said.
Subgroup concerns
Committee members discussed the risk/benefit profile for three subgroups of patients – those with apolipoprotein E4 (apo E4) allele, patients taking an anticoagulant, and those with cerebral amyloid angiopathy (CAA).
In the apo E4 group, the study’s primary endpoint did not favor the drug, but secondary endpoints did.
“I think the general feeling [for apo E4 status] is that the risk/benefit still remains favorable, especially when looking across multiple endpoints,” said Dr. Alexander.
However, some members supported recommending genetic testing before initiating the drug.
The views were more diverse for the use of lecanemab in the presence of an anticoagulant, which may increase the risk for cerebral hemorrhage. Some committee members strongly recommended that these patients not receive lecanemab, while others highlighted the need for more information, owing to uncertainties about the risks.
With respect to CAA, most members supported the idea of considering use of the drug in the presence of this condition, but only after discussing the risks with patients and their families and in the presence of a robust reporting system.
An Alzheimer’s Association representative was in attendance during the public hearing portion of the meeting to express support for traditional approval of lecanemab for people with early AD.
The association strongly favors full Medicare coverage for FDA-approved AD treatments. The Centers for Medicare & Medicaid Services has determined that AD treatments receiving traditional FDA approval will be covered if clinicians register and enter data in a registry.
“While this is an important signal that CMS wants to improve access to FDA-approved treatments, registry as a condition of coverage is an unnecessary and potentially harmful barrier,” said the Alzheimer’s Association in a press release following the meeting.
A version of this article first appeared on Medscape.com.
CMS to cover Alzheimer’s drugs after traditional FDA okay
The Centers for Medicare & Medicaid Services has announced that
The one caveat is that CMS will require physicians to participate in registries that collect evidence about how these drugs work in the real world.
Physicians will be able to submit this evidence through a nationwide, CMS-facilitated portal that will be available when any product gains traditional approval and will collect information via an easy-to-use format.
“If the FDA grants traditional approval, then Medicare will cover it in appropriate settings that also support the collection of real-world information to study the usefulness of these drugs for people with Medicare,” the CMS says in a news release.
“CMS has always been committed to helping people obtain timely access to innovative treatments that meaningfully improve care and outcomes for this disease,” added CMS Administrator Chiquita Brooks-LaSure.
“If the FDA grants traditional approval, CMS is prepared to ensure anyone with Medicare Part B who meets the criteria is covered,” Ms. Brooks-LaSure explained.
The CMS says broader Medicare coverage for an Alzheimer’s drug would begin on the same day the FDA grants traditional approval. Under CMS’ current coverage policy, if the FDA grants traditional approval to other drugs in this class, they would also be eligible for broader coverage.
Currently two drugs in this class – aducanumab (Aduhelm) and lecanemab (Leqembi) – have received accelerated approval from the FDA, but no product has received traditional approval.
Lecanemab might be the first to cross the line.
On June 9, the FDA Peripheral and Central Nervous System Drugs Advisory Committee will discuss results of a confirmatory trial of lecanemab, with a potential decision on traditional approval expected shortly thereafter.
A version of this article first appeared on Medscape.com.
The Centers for Medicare & Medicaid Services has announced that
The one caveat is that CMS will require physicians to participate in registries that collect evidence about how these drugs work in the real world.
Physicians will be able to submit this evidence through a nationwide, CMS-facilitated portal that will be available when any product gains traditional approval and will collect information via an easy-to-use format.
“If the FDA grants traditional approval, then Medicare will cover it in appropriate settings that also support the collection of real-world information to study the usefulness of these drugs for people with Medicare,” the CMS says in a news release.
“CMS has always been committed to helping people obtain timely access to innovative treatments that meaningfully improve care and outcomes for this disease,” added CMS Administrator Chiquita Brooks-LaSure.
“If the FDA grants traditional approval, CMS is prepared to ensure anyone with Medicare Part B who meets the criteria is covered,” Ms. Brooks-LaSure explained.
The CMS says broader Medicare coverage for an Alzheimer’s drug would begin on the same day the FDA grants traditional approval. Under CMS’ current coverage policy, if the FDA grants traditional approval to other drugs in this class, they would also be eligible for broader coverage.
Currently two drugs in this class – aducanumab (Aduhelm) and lecanemab (Leqembi) – have received accelerated approval from the FDA, but no product has received traditional approval.
Lecanemab might be the first to cross the line.
On June 9, the FDA Peripheral and Central Nervous System Drugs Advisory Committee will discuss results of a confirmatory trial of lecanemab, with a potential decision on traditional approval expected shortly thereafter.
A version of this article first appeared on Medscape.com.
The Centers for Medicare & Medicaid Services has announced that
The one caveat is that CMS will require physicians to participate in registries that collect evidence about how these drugs work in the real world.
Physicians will be able to submit this evidence through a nationwide, CMS-facilitated portal that will be available when any product gains traditional approval and will collect information via an easy-to-use format.
“If the FDA grants traditional approval, then Medicare will cover it in appropriate settings that also support the collection of real-world information to study the usefulness of these drugs for people with Medicare,” the CMS says in a news release.
“CMS has always been committed to helping people obtain timely access to innovative treatments that meaningfully improve care and outcomes for this disease,” added CMS Administrator Chiquita Brooks-LaSure.
“If the FDA grants traditional approval, CMS is prepared to ensure anyone with Medicare Part B who meets the criteria is covered,” Ms. Brooks-LaSure explained.
The CMS says broader Medicare coverage for an Alzheimer’s drug would begin on the same day the FDA grants traditional approval. Under CMS’ current coverage policy, if the FDA grants traditional approval to other drugs in this class, they would also be eligible for broader coverage.
Currently two drugs in this class – aducanumab (Aduhelm) and lecanemab (Leqembi) – have received accelerated approval from the FDA, but no product has received traditional approval.
Lecanemab might be the first to cross the line.
On June 9, the FDA Peripheral and Central Nervous System Drugs Advisory Committee will discuss results of a confirmatory trial of lecanemab, with a potential decision on traditional approval expected shortly thereafter.
A version of this article first appeared on Medscape.com.
FDA approves buprenorphine injection for opioid use disorder
The medication comes in two formulations: a weekly and a monthly version. The weekly treatment is indicated in patients who have initiated treatment with a single dose of transmucosal buprenorphine or who are already being treated with the drug. The monthly version is for patients already receiving buprenorphine.
“Buprenorphine is an important treatment option for opioid use disorder. Today’s approval expands dosing options and provides people with opioid use disorder a greater opportunity to sustain long-term recovery,” said FDA Commissioner Robert M. Califf, MD, in a release. “The FDA will continue to take the critical steps necessary to pursue efforts that advance evidence-based treatments for substance use disorders, which is a strategic priority under the FDA’s Overdose Prevention Framework,” Dr. Califf added.
The Substance Abuse and Mental Health Services Administration reports that patients receiving medication for OUD have their risk for all-cause mortality cut by 50%.
In its release, the FDA said that it remains committed to increasing treatment options for OUD. Earlier this month, the agency issued a joint letter with SAMHSA to underscore the importance of counseling and other services as part of a comprehensive treatment plan the disorder. It also emphasized that receiving buprenorphine should not be contingent on participating in such services.
Brixadi is approved in both weekly and monthly subcutaneous injectable formulations at varying doses, including lower doses that may be appropriate for patients who do not tolerate higher doses of extended-release buprenorphine that are currently available.
The drug will be available through a Risk Evaluation and Mitigation Strategy program and administered only by health care providers in a health care setting.
The most common adverse reactions associated with the drug include injection-site pain, headache, constipation, nausea, injection-site erythema, injection-site pruritus, insomnia, and urinary tract infections. The FDA reports that such side effects occur in at least 5% of patients.
A version of this article originally appeared on Medscape.com.
The medication comes in two formulations: a weekly and a monthly version. The weekly treatment is indicated in patients who have initiated treatment with a single dose of transmucosal buprenorphine or who are already being treated with the drug. The monthly version is for patients already receiving buprenorphine.
“Buprenorphine is an important treatment option for opioid use disorder. Today’s approval expands dosing options and provides people with opioid use disorder a greater opportunity to sustain long-term recovery,” said FDA Commissioner Robert M. Califf, MD, in a release. “The FDA will continue to take the critical steps necessary to pursue efforts that advance evidence-based treatments for substance use disorders, which is a strategic priority under the FDA’s Overdose Prevention Framework,” Dr. Califf added.
The Substance Abuse and Mental Health Services Administration reports that patients receiving medication for OUD have their risk for all-cause mortality cut by 50%.
In its release, the FDA said that it remains committed to increasing treatment options for OUD. Earlier this month, the agency issued a joint letter with SAMHSA to underscore the importance of counseling and other services as part of a comprehensive treatment plan the disorder. It also emphasized that receiving buprenorphine should not be contingent on participating in such services.
Brixadi is approved in both weekly and monthly subcutaneous injectable formulations at varying doses, including lower doses that may be appropriate for patients who do not tolerate higher doses of extended-release buprenorphine that are currently available.
The drug will be available through a Risk Evaluation and Mitigation Strategy program and administered only by health care providers in a health care setting.
The most common adverse reactions associated with the drug include injection-site pain, headache, constipation, nausea, injection-site erythema, injection-site pruritus, insomnia, and urinary tract infections. The FDA reports that such side effects occur in at least 5% of patients.
A version of this article originally appeared on Medscape.com.
The medication comes in two formulations: a weekly and a monthly version. The weekly treatment is indicated in patients who have initiated treatment with a single dose of transmucosal buprenorphine or who are already being treated with the drug. The monthly version is for patients already receiving buprenorphine.
“Buprenorphine is an important treatment option for opioid use disorder. Today’s approval expands dosing options and provides people with opioid use disorder a greater opportunity to sustain long-term recovery,” said FDA Commissioner Robert M. Califf, MD, in a release. “The FDA will continue to take the critical steps necessary to pursue efforts that advance evidence-based treatments for substance use disorders, which is a strategic priority under the FDA’s Overdose Prevention Framework,” Dr. Califf added.
The Substance Abuse and Mental Health Services Administration reports that patients receiving medication for OUD have their risk for all-cause mortality cut by 50%.
In its release, the FDA said that it remains committed to increasing treatment options for OUD. Earlier this month, the agency issued a joint letter with SAMHSA to underscore the importance of counseling and other services as part of a comprehensive treatment plan the disorder. It also emphasized that receiving buprenorphine should not be contingent on participating in such services.
Brixadi is approved in both weekly and monthly subcutaneous injectable formulations at varying doses, including lower doses that may be appropriate for patients who do not tolerate higher doses of extended-release buprenorphine that are currently available.
The drug will be available through a Risk Evaluation and Mitigation Strategy program and administered only by health care providers in a health care setting.
The most common adverse reactions associated with the drug include injection-site pain, headache, constipation, nausea, injection-site erythema, injection-site pruritus, insomnia, and urinary tract infections. The FDA reports that such side effects occur in at least 5% of patients.
A version of this article originally appeared on Medscape.com.
FDA approves new indication for avapritinib
Avapritinib, a selective KIT mutation-targeted tyrosine kinase inhibitor, was approved in 2021 to treat advanced systemic mastocytosis, a rare and potentially fatal hematologic disorder. Nonadvanced forms include indolent or smoldering disease; advanced disease can progress to leukemia. The expanded approval now covers patients with indolent disease, which represents the majority of patients with systemic mastocytosis.
The drug is also approved for adults with unresectable or metastatic GIST that harbors a platelet-derived growth factor receptor alpha exon 18 mutation.
The approval is based on data from the phase 2 PIONEER trial. In the trial, 222 patients with moderate to severe indolent, systemic mastocytosis* were randomly assigned in a 2:1 ratio to receive either avapritinib 25 mg once daily plus best supportive care or placebo plus best supportive care.
The findings, published in February, revealed that patients who received avapritinib experienced significantly greater improvements in total symptom scores at 24 weeks (–15.6 vs. –9.2 for control patients). Significantly more patients in the avapritinib arm achieved greater than or equal to 50% reductions in serum tryptase (54% vs. 0%), bone marrow mast cell aggregates (53% vs. 23%), and KIT D816V variant allele fraction (68% vs. 6%).
Most adverse reactions were mild to moderate in severity and included eye edema, dizziness, peripheral edema, and flushing. Fewer than 1% of patients discontinued treatment because of serious adverse reactions.
“People with indolent systemic mastocytosis are significantly impacted by their disease symptoms, and many individuals self-isolate at home to protect against unpredictable external triggers,” Judith Kain Emmel, board chair of the Mast Cell Disease Society, said in the company press release. “Today’s approval is a historic moment for the [systemic mastocytosis] community and offers new hope for patients and their families.
A version of this article first appeared on Medscape.com.
Correction, 5/23/23: An earlier version of this article mischaracterized these patients' conditions. They had moderate to severe indolent, systemic mastocytosis.
Avapritinib, a selective KIT mutation-targeted tyrosine kinase inhibitor, was approved in 2021 to treat advanced systemic mastocytosis, a rare and potentially fatal hematologic disorder. Nonadvanced forms include indolent or smoldering disease; advanced disease can progress to leukemia. The expanded approval now covers patients with indolent disease, which represents the majority of patients with systemic mastocytosis.
The drug is also approved for adults with unresectable or metastatic GIST that harbors a platelet-derived growth factor receptor alpha exon 18 mutation.
The approval is based on data from the phase 2 PIONEER trial. In the trial, 222 patients with moderate to severe indolent, systemic mastocytosis* were randomly assigned in a 2:1 ratio to receive either avapritinib 25 mg once daily plus best supportive care or placebo plus best supportive care.
The findings, published in February, revealed that patients who received avapritinib experienced significantly greater improvements in total symptom scores at 24 weeks (–15.6 vs. –9.2 for control patients). Significantly more patients in the avapritinib arm achieved greater than or equal to 50% reductions in serum tryptase (54% vs. 0%), bone marrow mast cell aggregates (53% vs. 23%), and KIT D816V variant allele fraction (68% vs. 6%).
Most adverse reactions were mild to moderate in severity and included eye edema, dizziness, peripheral edema, and flushing. Fewer than 1% of patients discontinued treatment because of serious adverse reactions.
“People with indolent systemic mastocytosis are significantly impacted by their disease symptoms, and many individuals self-isolate at home to protect against unpredictable external triggers,” Judith Kain Emmel, board chair of the Mast Cell Disease Society, said in the company press release. “Today’s approval is a historic moment for the [systemic mastocytosis] community and offers new hope for patients and their families.
A version of this article first appeared on Medscape.com.
Correction, 5/23/23: An earlier version of this article mischaracterized these patients' conditions. They had moderate to severe indolent, systemic mastocytosis.
Avapritinib, a selective KIT mutation-targeted tyrosine kinase inhibitor, was approved in 2021 to treat advanced systemic mastocytosis, a rare and potentially fatal hematologic disorder. Nonadvanced forms include indolent or smoldering disease; advanced disease can progress to leukemia. The expanded approval now covers patients with indolent disease, which represents the majority of patients with systemic mastocytosis.
The drug is also approved for adults with unresectable or metastatic GIST that harbors a platelet-derived growth factor receptor alpha exon 18 mutation.
The approval is based on data from the phase 2 PIONEER trial. In the trial, 222 patients with moderate to severe indolent, systemic mastocytosis* were randomly assigned in a 2:1 ratio to receive either avapritinib 25 mg once daily plus best supportive care or placebo plus best supportive care.
The findings, published in February, revealed that patients who received avapritinib experienced significantly greater improvements in total symptom scores at 24 weeks (–15.6 vs. –9.2 for control patients). Significantly more patients in the avapritinib arm achieved greater than or equal to 50% reductions in serum tryptase (54% vs. 0%), bone marrow mast cell aggregates (53% vs. 23%), and KIT D816V variant allele fraction (68% vs. 6%).
Most adverse reactions were mild to moderate in severity and included eye edema, dizziness, peripheral edema, and flushing. Fewer than 1% of patients discontinued treatment because of serious adverse reactions.
“People with indolent systemic mastocytosis are significantly impacted by their disease symptoms, and many individuals self-isolate at home to protect against unpredictable external triggers,” Judith Kain Emmel, board chair of the Mast Cell Disease Society, said in the company press release. “Today’s approval is a historic moment for the [systemic mastocytosis] community and offers new hope for patients and their families.
A version of this article first appeared on Medscape.com.
Correction, 5/23/23: An earlier version of this article mischaracterized these patients' conditions. They had moderate to severe indolent, systemic mastocytosis.
FDA advisory committee votes against approval for NASH drug
The Food and Drug Administration’s Gastrointestinal Drugs Advisory Committee has voted against the accelerated approval of Intercept Pharmaceuticals’ obeticholic acid (OCA) for treatment of nonalcoholic steatohepatitis (NASH) with stage 2 or 3 fibrosis.
This is the second time that Intercept has sought FDA approval for OCA in treating NASH.
The committee voted 12 to 2 (with 2 abstentions) that the benefits of OCA did not outweigh the risks to this patient population. While OCA showed a modest benefit of improving fibrosis in NASH patients, safety concerns included increased risk for drug-induced liver injury (DILI), cholelithiasis, pruritus, dyslipidemia, and dysglycemia.
Committee members were most concerned with the increased risk for DILI in patients taking OCA. Intercept said that frequent monitoring for DILI in such a large eligible population – an estimated 6-8 million individuals taking the drug to treat the condition – would be difficult.
“Typically, in clinical practice, NASH patients are followed every 6-12 months, so more frequent monitoring would be a substantial change and may not be achievable outside of the clinical trial setting,” according to a briefing document released before the committee meeting.
The FDA estimates that 16.8 million U.S. adults have NASH, with 5.7 million having NASH with advanced fibrosis, according to briefing documents. NASH is the second leading cause of liver transplants in the United States and is the leading cause in women. There are currently no FDA-approved therapies to treat NASH.
OCA, sold under the commercial name Ocaliva, was first approved in 2016 to treat primary biliary cholangitis, and is prescribed at up to 10 mg per day. Intercept proposed that OCA be given in daily 25-mg doses in the treatment of precirrhotic fibrosis attributable to NASH.
In 2019, Intercept initially filed for a new drug application (NDA) for OCA for the treatment of precirrhotic fibrosis attributable to NASH but were issued a Complete Response Letter after the FDA determined that the medication had an “unfavorable risk benefit-risk assessment.” Intercept resubmitted an NDA for OCA in December 2022, including two 18-month analyses from a phase 3 study, REGENERATE (Randomized Global Phase 3 Study to Evaluate the Impact on NASH with Fibrosis of Obeticholic Acid Treatment). In the study, which included data from 931 patients, OCA 25 mg outperformed placebo in improving fibrosis with no worsening of NASH over 18 months, one of two primary endpoints of the clinical trial. The estimated risk difference ranged from 8.6 to 12.8 across different analyses, which the FDA categorized as a “modest treatment effect.”
There was no significant difference between OCA 25 mg and placebo in NASH resolution with no worsening fibrosis. Both endpoints were surrogate endpoints, meaning that they were “reasonably likely to predict clinical benefit.” The FDA noted that it is not known if a decrease in fibrosis stage would lead to clinically meaningful outcomes, such as reduction in liver-related events.
The committee members voted 15-1 to defer approval until clinical outcome data is submitted and reviewed. The FDA has set a target decision date regarding the accelerated approval of OCA for NASH for June 22, 2023.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration’s Gastrointestinal Drugs Advisory Committee has voted against the accelerated approval of Intercept Pharmaceuticals’ obeticholic acid (OCA) for treatment of nonalcoholic steatohepatitis (NASH) with stage 2 or 3 fibrosis.
This is the second time that Intercept has sought FDA approval for OCA in treating NASH.
The committee voted 12 to 2 (with 2 abstentions) that the benefits of OCA did not outweigh the risks to this patient population. While OCA showed a modest benefit of improving fibrosis in NASH patients, safety concerns included increased risk for drug-induced liver injury (DILI), cholelithiasis, pruritus, dyslipidemia, and dysglycemia.
Committee members were most concerned with the increased risk for DILI in patients taking OCA. Intercept said that frequent monitoring for DILI in such a large eligible population – an estimated 6-8 million individuals taking the drug to treat the condition – would be difficult.
“Typically, in clinical practice, NASH patients are followed every 6-12 months, so more frequent monitoring would be a substantial change and may not be achievable outside of the clinical trial setting,” according to a briefing document released before the committee meeting.
The FDA estimates that 16.8 million U.S. adults have NASH, with 5.7 million having NASH with advanced fibrosis, according to briefing documents. NASH is the second leading cause of liver transplants in the United States and is the leading cause in women. There are currently no FDA-approved therapies to treat NASH.
OCA, sold under the commercial name Ocaliva, was first approved in 2016 to treat primary biliary cholangitis, and is prescribed at up to 10 mg per day. Intercept proposed that OCA be given in daily 25-mg doses in the treatment of precirrhotic fibrosis attributable to NASH.
In 2019, Intercept initially filed for a new drug application (NDA) for OCA for the treatment of precirrhotic fibrosis attributable to NASH but were issued a Complete Response Letter after the FDA determined that the medication had an “unfavorable risk benefit-risk assessment.” Intercept resubmitted an NDA for OCA in December 2022, including two 18-month analyses from a phase 3 study, REGENERATE (Randomized Global Phase 3 Study to Evaluate the Impact on NASH with Fibrosis of Obeticholic Acid Treatment). In the study, which included data from 931 patients, OCA 25 mg outperformed placebo in improving fibrosis with no worsening of NASH over 18 months, one of two primary endpoints of the clinical trial. The estimated risk difference ranged from 8.6 to 12.8 across different analyses, which the FDA categorized as a “modest treatment effect.”
There was no significant difference between OCA 25 mg and placebo in NASH resolution with no worsening fibrosis. Both endpoints were surrogate endpoints, meaning that they were “reasonably likely to predict clinical benefit.” The FDA noted that it is not known if a decrease in fibrosis stage would lead to clinically meaningful outcomes, such as reduction in liver-related events.
The committee members voted 15-1 to defer approval until clinical outcome data is submitted and reviewed. The FDA has set a target decision date regarding the accelerated approval of OCA for NASH for June 22, 2023.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration’s Gastrointestinal Drugs Advisory Committee has voted against the accelerated approval of Intercept Pharmaceuticals’ obeticholic acid (OCA) for treatment of nonalcoholic steatohepatitis (NASH) with stage 2 or 3 fibrosis.
This is the second time that Intercept has sought FDA approval for OCA in treating NASH.
The committee voted 12 to 2 (with 2 abstentions) that the benefits of OCA did not outweigh the risks to this patient population. While OCA showed a modest benefit of improving fibrosis in NASH patients, safety concerns included increased risk for drug-induced liver injury (DILI), cholelithiasis, pruritus, dyslipidemia, and dysglycemia.
Committee members were most concerned with the increased risk for DILI in patients taking OCA. Intercept said that frequent monitoring for DILI in such a large eligible population – an estimated 6-8 million individuals taking the drug to treat the condition – would be difficult.
“Typically, in clinical practice, NASH patients are followed every 6-12 months, so more frequent monitoring would be a substantial change and may not be achievable outside of the clinical trial setting,” according to a briefing document released before the committee meeting.
The FDA estimates that 16.8 million U.S. adults have NASH, with 5.7 million having NASH with advanced fibrosis, according to briefing documents. NASH is the second leading cause of liver transplants in the United States and is the leading cause in women. There are currently no FDA-approved therapies to treat NASH.
OCA, sold under the commercial name Ocaliva, was first approved in 2016 to treat primary biliary cholangitis, and is prescribed at up to 10 mg per day. Intercept proposed that OCA be given in daily 25-mg doses in the treatment of precirrhotic fibrosis attributable to NASH.
In 2019, Intercept initially filed for a new drug application (NDA) for OCA for the treatment of precirrhotic fibrosis attributable to NASH but were issued a Complete Response Letter after the FDA determined that the medication had an “unfavorable risk benefit-risk assessment.” Intercept resubmitted an NDA for OCA in December 2022, including two 18-month analyses from a phase 3 study, REGENERATE (Randomized Global Phase 3 Study to Evaluate the Impact on NASH with Fibrosis of Obeticholic Acid Treatment). In the study, which included data from 931 patients, OCA 25 mg outperformed placebo in improving fibrosis with no worsening of NASH over 18 months, one of two primary endpoints of the clinical trial. The estimated risk difference ranged from 8.6 to 12.8 across different analyses, which the FDA categorized as a “modest treatment effect.”
There was no significant difference between OCA 25 mg and placebo in NASH resolution with no worsening fibrosis. Both endpoints were surrogate endpoints, meaning that they were “reasonably likely to predict clinical benefit.” The FDA noted that it is not known if a decrease in fibrosis stage would lead to clinically meaningful outcomes, such as reduction in liver-related events.
The committee members voted 15-1 to defer approval until clinical outcome data is submitted and reviewed. The FDA has set a target decision date regarding the accelerated approval of OCA for NASH for June 22, 2023.
A version of this article first appeared on Medscape.com.
FDA approves epcoritamab for r/r DLBCL
Epcoritamab is the first subcutaneous bispecific antibody approved for the indication. The biologic simultaneously binds CD3 on cytotoxic T cells to CD20 on lymphomic B cells, inducing T-cell mediated destruction.
“Together with our partner, AbbVie, we recognize the unmet need for safe, effective, and accessible treatments for patients with B-cell malignancies and we believe that epcoritamab has the potential to become a core therapy in this patient population,” Jan van de Winkel, PhD, CEO of Genmab, said in a press release announcing the FDA’s acceptance of its biologic licensing application in November 2022.
A potential competitor, Roche’s bispecific antibody mosunetuzumab (Lunsumio), was approved in December 2022. Mosunetuzumab has the same mechanism of action as epcoritamab but is indicated for relapsed or refractory follicular lymphoma after at least two lines of systemic therapy. A phase 3 trial is currently underway exploring epcoritamab for relapsed or refractory follicular lymphoma as part of combination therapy.
The current approval was based on the open-label phase 2 EPCORE NHL-1 trial conducted by AbbVie and Genmab. The trial’s efficacy population included 148 adults with relapsed or refractory CD20+ large B-cell lymphoma who had received at least two prior lines of therapy, including anti-CD20 therapies. Almost 40% had undergone CAR-T cell therapy.
Epcoritamab was administered initially once weekly, then every 2 weeks, and then every 4 weeks until disease progression or unacceptable toxicity. The trial had no comparator arm.
At a median follow-up of 10.7 months, the overall response rate was 61% and the complete response rate was 38%. At a median follow-up of 9.8 months among responders, the median duration of response was 15.6 months.
The prescribing information comes with a boxed warning for serious or life-threatening cytokine release syndrome and life-threatening or fatal immune effector cell–associated neurotoxicity syndrome. Warnings and precautions include infections and cytopenias.
Among the 157 patients who received epcoritamab in the trial at the recommended dose, grade 1-3 cytokine release syndrome occurred in 51%, immune effector cell–associated neurotoxicity syndrome occurred in 6% (with one fatal case), and 15% experienced serious infections.
The most common grade 3 or 4 events included neutropenia (14.6%), anemia (10.2%), and thrombocytopenia (5.7%).
The FDA recommends epcoritamab be administered subcutaneously in 28-day cycles until disease progression or unacceptable toxicity.
The FDA also noted that “this indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.”
A version of this article first appeared on Medscape.com.
Epcoritamab is the first subcutaneous bispecific antibody approved for the indication. The biologic simultaneously binds CD3 on cytotoxic T cells to CD20 on lymphomic B cells, inducing T-cell mediated destruction.
“Together with our partner, AbbVie, we recognize the unmet need for safe, effective, and accessible treatments for patients with B-cell malignancies and we believe that epcoritamab has the potential to become a core therapy in this patient population,” Jan van de Winkel, PhD, CEO of Genmab, said in a press release announcing the FDA’s acceptance of its biologic licensing application in November 2022.
A potential competitor, Roche’s bispecific antibody mosunetuzumab (Lunsumio), was approved in December 2022. Mosunetuzumab has the same mechanism of action as epcoritamab but is indicated for relapsed or refractory follicular lymphoma after at least two lines of systemic therapy. A phase 3 trial is currently underway exploring epcoritamab for relapsed or refractory follicular lymphoma as part of combination therapy.
The current approval was based on the open-label phase 2 EPCORE NHL-1 trial conducted by AbbVie and Genmab. The trial’s efficacy population included 148 adults with relapsed or refractory CD20+ large B-cell lymphoma who had received at least two prior lines of therapy, including anti-CD20 therapies. Almost 40% had undergone CAR-T cell therapy.
Epcoritamab was administered initially once weekly, then every 2 weeks, and then every 4 weeks until disease progression or unacceptable toxicity. The trial had no comparator arm.
At a median follow-up of 10.7 months, the overall response rate was 61% and the complete response rate was 38%. At a median follow-up of 9.8 months among responders, the median duration of response was 15.6 months.
The prescribing information comes with a boxed warning for serious or life-threatening cytokine release syndrome and life-threatening or fatal immune effector cell–associated neurotoxicity syndrome. Warnings and precautions include infections and cytopenias.
Among the 157 patients who received epcoritamab in the trial at the recommended dose, grade 1-3 cytokine release syndrome occurred in 51%, immune effector cell–associated neurotoxicity syndrome occurred in 6% (with one fatal case), and 15% experienced serious infections.
The most common grade 3 or 4 events included neutropenia (14.6%), anemia (10.2%), and thrombocytopenia (5.7%).
The FDA recommends epcoritamab be administered subcutaneously in 28-day cycles until disease progression or unacceptable toxicity.
The FDA also noted that “this indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.”
A version of this article first appeared on Medscape.com.
Epcoritamab is the first subcutaneous bispecific antibody approved for the indication. The biologic simultaneously binds CD3 on cytotoxic T cells to CD20 on lymphomic B cells, inducing T-cell mediated destruction.
“Together with our partner, AbbVie, we recognize the unmet need for safe, effective, and accessible treatments for patients with B-cell malignancies and we believe that epcoritamab has the potential to become a core therapy in this patient population,” Jan van de Winkel, PhD, CEO of Genmab, said in a press release announcing the FDA’s acceptance of its biologic licensing application in November 2022.
A potential competitor, Roche’s bispecific antibody mosunetuzumab (Lunsumio), was approved in December 2022. Mosunetuzumab has the same mechanism of action as epcoritamab but is indicated for relapsed or refractory follicular lymphoma after at least two lines of systemic therapy. A phase 3 trial is currently underway exploring epcoritamab for relapsed or refractory follicular lymphoma as part of combination therapy.
The current approval was based on the open-label phase 2 EPCORE NHL-1 trial conducted by AbbVie and Genmab. The trial’s efficacy population included 148 adults with relapsed or refractory CD20+ large B-cell lymphoma who had received at least two prior lines of therapy, including anti-CD20 therapies. Almost 40% had undergone CAR-T cell therapy.
Epcoritamab was administered initially once weekly, then every 2 weeks, and then every 4 weeks until disease progression or unacceptable toxicity. The trial had no comparator arm.
At a median follow-up of 10.7 months, the overall response rate was 61% and the complete response rate was 38%. At a median follow-up of 9.8 months among responders, the median duration of response was 15.6 months.
The prescribing information comes with a boxed warning for serious or life-threatening cytokine release syndrome and life-threatening or fatal immune effector cell–associated neurotoxicity syndrome. Warnings and precautions include infections and cytopenias.
Among the 157 patients who received epcoritamab in the trial at the recommended dose, grade 1-3 cytokine release syndrome occurred in 51%, immune effector cell–associated neurotoxicity syndrome occurred in 6% (with one fatal case), and 15% experienced serious infections.
The most common grade 3 or 4 events included neutropenia (14.6%), anemia (10.2%), and thrombocytopenia (5.7%).
The FDA recommends epcoritamab be administered subcutaneously in 28-day cycles until disease progression or unacceptable toxicity.
The FDA also noted that “this indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.”
A version of this article first appeared on Medscape.com.
FDA approves upadacitinib for Crohn’s disease
whose condition failed to respond adequately or who can’t tolerate one or more tumor necrosis factor (TNF) inhibitors, the company has announced.
Upadacitinib (Rinvoq, AbbVie) is the first oral small molecule approved by the FDA for Crohn’s disease, which is noteworthy, said Kristin E. Burke, MD, MPH, medical director of clinical operations for the Massachusetts General Hospital Crohn’s and Colitis Center, Boston.
“Crohn’s disease is a complex immune-mediated disease for which more effective and fast-acting treatment options are needed. The approval of upadacitinib for anti-TNF refractory Crohn’s disease represents an important milestone in the expansion of treatment options for this disease as the first oral small molecule available,” she said.
The approval for Crohn’s disease was supported by data from two induction studies (U-EXCEED and U-EXCEL) and one maintenance study (U-ENDURE).
In the two induction studies, 857 patients were randomly assigned to receive upadacitinib 45 mg or placebo once daily for 12 weeks. At week 12, a greater proportion of patients who received upadacitinib (vs. those who received placebo) achieved clinical remission, as determined on the basis of the Crohn’s Disease Activity Index (CDAI), and improvement in intestinal inflammation as assessed by colonoscopy.
In the maintenance study, 343 patients who responded to induction therapy with upadacitinib were randomly assigned to receive either a maintenance regimen of 15 or 30 mg once daily or placebo for 52 weeks.
At week 52, a greater proportion of patients who were treated with upadacitinib 15 mg or 30 mg, compared with those who received placebo, achieved clinical remission.
Data from the trials of upadacitinib in Crohn’s disease were presented at the European Crohn’s and Colitis Organisation (ECCO) 2023 Congress in March.
“Symptoms of moderately to severely active Crohn’s disease can be disruptive and uncomfortable for patients, so relief as early as possible is key. Given the progressive nature of the disease, endoscopic response is just as important,” U-EXCEL study investigator Edward V. Loftus Jr., MD, professor of medicine in the division of gastroenterology and hepatology at Mayo Clinic in Rochester, Minn., said in a news release.
“Based on the clinical trial results, treatment with Rinvoq shows both early and long-term symptom relief along with evidence of a visible reduction of damage to the intestinal lining caused by excess inflammation,” he said.
Patients should initially be given 45 mg of upadacitinib once daily for 12 weeks. After 12 weeks, the recommended maintenance dosage is 15 mg once a day. A maintenance dose of 30 mg once daily can be considered for patients with refractory, severe, or extensive Crohn’s disease, the FDA said in a statement announcing approval.
The most common side effects of upadacitinib in patients with Crohn’s disease are upper respiratory tract infection, anemia, fever, acne, herpes zoster, and headache.
Upadacitinib is not recommended for use in combination with other JAK inhibitors, biological therapies for Crohn’s disease, or with strong immunosuppressants, such as azathioprine and cyclosporine.
Serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis have occurred with JAK inhibitors such as upadacitinib.
The indication in Crohn’s disease marks the seventh in the United States for the JAK inhibitor. Other indications include rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.
Full prescribing information is available online.
Dr. Burke disclosed no conflicts. Dr. Loftus is a consultant and adviser for AbbVie.
A version of this article first appeared on Medscape.com.
whose condition failed to respond adequately or who can’t tolerate one or more tumor necrosis factor (TNF) inhibitors, the company has announced.
Upadacitinib (Rinvoq, AbbVie) is the first oral small molecule approved by the FDA for Crohn’s disease, which is noteworthy, said Kristin E. Burke, MD, MPH, medical director of clinical operations for the Massachusetts General Hospital Crohn’s and Colitis Center, Boston.
“Crohn’s disease is a complex immune-mediated disease for which more effective and fast-acting treatment options are needed. The approval of upadacitinib for anti-TNF refractory Crohn’s disease represents an important milestone in the expansion of treatment options for this disease as the first oral small molecule available,” she said.
The approval for Crohn’s disease was supported by data from two induction studies (U-EXCEED and U-EXCEL) and one maintenance study (U-ENDURE).
In the two induction studies, 857 patients were randomly assigned to receive upadacitinib 45 mg or placebo once daily for 12 weeks. At week 12, a greater proportion of patients who received upadacitinib (vs. those who received placebo) achieved clinical remission, as determined on the basis of the Crohn’s Disease Activity Index (CDAI), and improvement in intestinal inflammation as assessed by colonoscopy.
In the maintenance study, 343 patients who responded to induction therapy with upadacitinib were randomly assigned to receive either a maintenance regimen of 15 or 30 mg once daily or placebo for 52 weeks.
At week 52, a greater proportion of patients who were treated with upadacitinib 15 mg or 30 mg, compared with those who received placebo, achieved clinical remission.
Data from the trials of upadacitinib in Crohn’s disease were presented at the European Crohn’s and Colitis Organisation (ECCO) 2023 Congress in March.
“Symptoms of moderately to severely active Crohn’s disease can be disruptive and uncomfortable for patients, so relief as early as possible is key. Given the progressive nature of the disease, endoscopic response is just as important,” U-EXCEL study investigator Edward V. Loftus Jr., MD, professor of medicine in the division of gastroenterology and hepatology at Mayo Clinic in Rochester, Minn., said in a news release.
“Based on the clinical trial results, treatment with Rinvoq shows both early and long-term symptom relief along with evidence of a visible reduction of damage to the intestinal lining caused by excess inflammation,” he said.
Patients should initially be given 45 mg of upadacitinib once daily for 12 weeks. After 12 weeks, the recommended maintenance dosage is 15 mg once a day. A maintenance dose of 30 mg once daily can be considered for patients with refractory, severe, or extensive Crohn’s disease, the FDA said in a statement announcing approval.
The most common side effects of upadacitinib in patients with Crohn’s disease are upper respiratory tract infection, anemia, fever, acne, herpes zoster, and headache.
Upadacitinib is not recommended for use in combination with other JAK inhibitors, biological therapies for Crohn’s disease, or with strong immunosuppressants, such as azathioprine and cyclosporine.
Serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis have occurred with JAK inhibitors such as upadacitinib.
The indication in Crohn’s disease marks the seventh in the United States for the JAK inhibitor. Other indications include rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.
Full prescribing information is available online.
Dr. Burke disclosed no conflicts. Dr. Loftus is a consultant and adviser for AbbVie.
A version of this article first appeared on Medscape.com.
whose condition failed to respond adequately or who can’t tolerate one or more tumor necrosis factor (TNF) inhibitors, the company has announced.
Upadacitinib (Rinvoq, AbbVie) is the first oral small molecule approved by the FDA for Crohn’s disease, which is noteworthy, said Kristin E. Burke, MD, MPH, medical director of clinical operations for the Massachusetts General Hospital Crohn’s and Colitis Center, Boston.
“Crohn’s disease is a complex immune-mediated disease for which more effective and fast-acting treatment options are needed. The approval of upadacitinib for anti-TNF refractory Crohn’s disease represents an important milestone in the expansion of treatment options for this disease as the first oral small molecule available,” she said.
The approval for Crohn’s disease was supported by data from two induction studies (U-EXCEED and U-EXCEL) and one maintenance study (U-ENDURE).
In the two induction studies, 857 patients were randomly assigned to receive upadacitinib 45 mg or placebo once daily for 12 weeks. At week 12, a greater proportion of patients who received upadacitinib (vs. those who received placebo) achieved clinical remission, as determined on the basis of the Crohn’s Disease Activity Index (CDAI), and improvement in intestinal inflammation as assessed by colonoscopy.
In the maintenance study, 343 patients who responded to induction therapy with upadacitinib were randomly assigned to receive either a maintenance regimen of 15 or 30 mg once daily or placebo for 52 weeks.
At week 52, a greater proportion of patients who were treated with upadacitinib 15 mg or 30 mg, compared with those who received placebo, achieved clinical remission.
Data from the trials of upadacitinib in Crohn’s disease were presented at the European Crohn’s and Colitis Organisation (ECCO) 2023 Congress in March.
“Symptoms of moderately to severely active Crohn’s disease can be disruptive and uncomfortable for patients, so relief as early as possible is key. Given the progressive nature of the disease, endoscopic response is just as important,” U-EXCEL study investigator Edward V. Loftus Jr., MD, professor of medicine in the division of gastroenterology and hepatology at Mayo Clinic in Rochester, Minn., said in a news release.
“Based on the clinical trial results, treatment with Rinvoq shows both early and long-term symptom relief along with evidence of a visible reduction of damage to the intestinal lining caused by excess inflammation,” he said.
Patients should initially be given 45 mg of upadacitinib once daily for 12 weeks. After 12 weeks, the recommended maintenance dosage is 15 mg once a day. A maintenance dose of 30 mg once daily can be considered for patients with refractory, severe, or extensive Crohn’s disease, the FDA said in a statement announcing approval.
The most common side effects of upadacitinib in patients with Crohn’s disease are upper respiratory tract infection, anemia, fever, acne, herpes zoster, and headache.
Upadacitinib is not recommended for use in combination with other JAK inhibitors, biological therapies for Crohn’s disease, or with strong immunosuppressants, such as azathioprine and cyclosporine.
Serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis have occurred with JAK inhibitors such as upadacitinib.
The indication in Crohn’s disease marks the seventh in the United States for the JAK inhibitor. Other indications include rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.
Full prescribing information is available online.
Dr. Burke disclosed no conflicts. Dr. Loftus is a consultant and adviser for AbbVie.
A version of this article first appeared on Medscape.com.