The drug was approved by the FDA in June, with the agency asking for a new randomized controlled clinical trial to verify the drug’s clinical benefit.
Biogen has now submitted the final study protocol for the Phase 4 Envision trial to the FDA for review. It expects to start patient screening in May; with the primary completion of the trial expected four years after the start of the study.
Aduhelm (aducanumab-avwa) represents the first new treatment approved for Alzheimer’s since 2003 and is the first therapy that targets the fundamental pathophysiology of the disease.
In trials supporting the drug’s application for approval, patients receiving the treatment had significant dose-and time-dependent reduction of amyloid beta plaque, while patients in the control arm of the studies had no reduction of amyloid beta plaque (amyloid beta plaque being a hallmark of Alzheimer’s disease).
However, the link between amyloid beta reduction and clinical improvement has been questioned (the European Medicines Agency, for example, said this link ‘has not been established’ when it rejected the drug’s application in December)
The Phase 4 study will be a global, placebo-controlled trial, aiming to enroll around 1,500 patients with early Alzheimer’s disease and confirmation of amyloid beta pathology.
The primary endpoint for the trial will be measured by the Clinical Dementia Rating–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, as well as the Alzheimer's Disease Assessment 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-Mental State Examination (MMSE) and Neuropsychiatric Inventory (NPI-10).
Biogen also re-affirms its commitment to create a diverse trial representing different patient populations: with at least 18% of patients set to come from Black/African American and Latino communities.
It is working with community groups such as the National Minority Quality Forum to overcome traditional enrolment barriers. To do this, it will select 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 swiftly and that the diversity of patients in it reflects that of Americans diagnosed with early Alzheimer’s disease,” said Samantha Budd Haeberlein, Ph.D., SVP, Head of Neurodegeneration Development at Biogen. “We plan to work hand-in-hand with underrepresented communities and Alzheimer’s disease groups to achieve our diversity and inclusion goal.”