The drug was approved by the FDA in June, with the agency requesting a new randomized controlled clinical trial to verify the drug’s clinical benefits.
Biogen has now submitted the final study protocol for the Phase 4 Envision trial to the FDA for review. He expects to start screening patients in May; with primary trial completion expected four years after study initiation.
Aduhelm (aducanumab-avwa) represents the first new treatment approved for Alzheimer’s disease since 2003 and is the first therapy to target the basic pathophysiology of the disease.
In trials supporting the drug’s application for approval, patients receiving the treatment showed a significant reduction in beta-amyloid plaque as a function of dose and time, while patients in the control group in studies n had no reduction in beta-amyloid plaque (beta-amyloid plaque being a hallmark of Alzheimer’s disease).
However, the link between reduced beta-amyloid and clinical improvement has been questioned (the European Medicines Agency, for example, said this link “has not been established” when it rejected the request for the drug in December)
The Phase 4 study will be a global, placebo-controlled trial, aiming to enroll approximately 1,500 patients with early-stage Alzheimer’s disease and confirm beta-amyloid pathology.
The primary endpoint of the trial will be measured by Clinical Rating of Dementia – Sum of Boxes (CDR-SB) at 18 months, as announced in January 2022. The trial will also include a planned long-term extension to collect treatment data for up to 48 months.
Secondary endpoints include changes in Amyloid Positron Emission Tomography (PET) and Tau PET scans, and the Alzheimer’s Disease Rating Scale – Cognitive Subscale (ADAS-Cog 13 ), Alzheimer’s Disease Cooperative Study – Activities of Daily Living Inventory – Mild Cognitive Impairment Version (ADCS-ADL-MCI), Integrated Alzheimer’s Disease Rating Scale (iADRS), Mini-Examination of Mental Health (MMSE) and the Neuropsychiatric Inventory (NPI-10).
Biogen also reaffirms its commitment to creating a diverse trial representing different patient populations: with at least 18% of patients from the Black/African American and Latino communities.
It works with community groups such as the National Minority Quality Forum to overcome traditional barriers to registration. It will do this by selecting sites with diverse staff, located in communities of color; support trial sites in identifying and engaging underrepresented communities; and engage with community and patient organizations to increase awareness of Alzheimer’s disease education and research.
“Our unwavering commitment is to ensure that the trial is completed quickly and that the diversity of patients participating reflects that of Americans diagnosed with early-stage Alzheimer’s disease,” said Samantha Budd Haeberlein, Ph.D., Senior Vice President, Neurodegeneration Development Lead at Biogen. “We plan to work hand-in-hand with underrepresented communities and groups with Alzheimer’s disease to achieve our goal of diversity and inclusion.