Aduhelm Phase 4 ENVISION Study to Increase Participant Diversity
Up to 18% of U.S. participants in ENVISION — a Phase 4 post-marketing study of Aduhelm (aducanumab) in early Alzheimer’s disease — will now be enrolled from African American and Latinx populations, the therapy’s developers said in a press release.
“Historically, patients from diverse backgrounds have been poorly represented in Alzheimer’s disease clinical trials, and we are committed to changing this,” said Priya Singhal, MD, of Biogen, the company that developed the therapy alongside Eisai, and is a sponsor of ENVISION.
“This goal matches the diversity among Americans diagnosed with early Alzheimer’s disease, while at the same time, the trial will generate substantial data to verify the effectiveness of Aduhelm,” added Singhal, the company’s head of global safety & regulatory sciences and interim head of R&D.
Biogen will attempt several measures to overcome barriers that limit the enrollment of diverse patients in Alzheimer’s trials. These strategies include addressing the lack of access to medical centers, providing greater education regarding the benefit-to-risk profile of Aduhelm, and offering help with financial or logistical difficulties.
According to the two companies, patient screening for the placebo-controlled ENVISION trial is planned for May of this year. The trial is expected to be completed about four years after its launch.
“It’s important to see this ambitious focus on diversity being prioritized in enrollment and integrated as a key part of the ENVISION clinical trial, so that we can have data from patients who more closely represent what we see in the clinic,” said Dylan Wint, MD, of the Cleveland Clinic Lou Ruvo Center for Brain Health, in Nevada.
The companies also had previously announced the inclusion of at least 16% Latinx and African American patients with Alzheimer’s disease in the ICARE AD trial. This trial will be a real-world observational study to evaluate the safety and efficacy of Aduhelm in clinical practice, with plans to enroll about 6,000 participants.
“This is an important step forward in ensuring that people of color have access to Alzheimer’s clinical trials,” George Vradenburg, chairman and co-founder of UsAgainstAlzheimer’s, said in a separate press release. UsAgainstAlzheimer’s is a patient advocacy organization that has been critical of the lack of diversity in Biogen’s early clinical trials.
“Biogen’s announcement represents progress in ensuring diversity in Alzheimer’s research, but the field itself still has a long way to go,” Vradenburg said.
Aduhelm is an antibody-based therapy designed to remove toxic clumps of beta-amyloid protein, which are thought to cause the death of nerve cells in the brains of people with Alzheimer’s.
Last year, Aduhelm, administered as an into-the-vein infusion, was granted accelerated approval in the U.S. for those with early-stage Alzheimer’s based on the results of clinical trials that showed the therapy reduced amyloid-beta clumps in the brain. Under accelerated approval, Biogen has nine years to market Aduhelm before completing the post-marketing study to confirm its clinical benefits.
ENVISION’s primary goal will be measured by the clinical dementia rating–sum of boxes (CDR-SB) at 18 months after treatment initiation — a validated assessment of cognition and function applied in clinical trials evaluating early symptomatic Alzheimer’s disease patients.
To strengthen the study’s statistical power, enrollment has been increased from 1,300 to 1,500 people with mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s disease who have amyloid-beta clumps.
Secondary outcomes will include the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 13), the Mini-Mental State Examination (MMSE), the Neuropsychiatric Inventory (NPI-10), the Alzheimer’s Disease Cooperative Study – Activities of Daily Living Inventory – Mild Cognitive Impairment Version (ADCS-ADL-MCI), and the Integrated Alzheimer’s Disease Rating Scale.
The U.S. Centers for Medicare and Medicaid Services (CMS) recently proposed that the cost of Aduhelm, and other antibody therapies with the same mechanism of action, be covered only for those enrolled in qualifying clinical trials. That proposal was met with outrage by both patient advocacy groups and Biogen. Medicare is the U.S. national program that provides health insurance coverage to people 65 and older.
Biogen said it will engage with CMS to avoid duplication of clinical trials and find a way to offer immediate access to patients.