Biogen has finally published the peer-reviewed results of its pivotal phase 3 clinical trials for Alzheimer's therapy Aduhelm (aducanumab), offering the medical community a detailed look at the data behind the controversial drug's FDA approval.
The publication in the Journal of Prevention of Alzheimer's Disease (JPAD) reveals divergent outcomes from the EMERGE and ENGAGE trials. While EMERGE demonstrated statistically significant improvements across primary and secondary clinical endpoints, including the Clinical Dementia Rating Sum of Boxes (CDR-SB) at week 78, the ENGAGE trial failed to meet its objectives.
Clinical Efficacy and Biomarker Data
The FDA's accelerated approval of Aduhelm was primarily based on the drug's ability to reduce amyloid beta plaques, a surrogate marker that Biogen correlates with cognitive benefits. New long-term extension data spanning up to two and a half years reveals continued effects on disease biomarkers, with sustained reduction in amyloid beta plaque levels through week 132 and decreased plasma p-tau181 levels at week 128.
Dr. Samantha Budd Haeberlein, Biogen's head of neurodegeneration development, emphasized the significance of these findings: "We are pleased that the peer-reviewed manuscript is now available to provide physicians with a greater understanding of the appropriate use of Aduhelm." She noted that participants showing reduced plasma p-tau181 at 78 weeks demonstrated decreased clinical decline, which the company considers a meaningful outcome.
Publication Controversy and Access Challenges
The choice of publication venue has raised eyebrows within the scientific community. JPAD, while established, is not considered among the top-tier medical journals typically selected for breakthrough therapeutic data. Adding to the controversy, JPAD's editor-in-chief Dr. Paul Aisen, who served as one of the lead investigators on the Aduhelm studies, is also a paid consultant for Biogen. While Dr. Aisen reportedly recused himself from the paper's review process, his dual role has sparked discussions about potential conflicts of interest.
Despite the publication of these results, Aduhelm's clinical adoption remains limited, largely due to proposed Medicare restrictions that would confine the drug's use to approved clinical trials. However, advocacy groups, led by USAgainstAlzheimer's, have launched a multi-million dollar advertising campaign to lobby for broader access to the treatment.
Future Implications
Biogen maintains its commitment to gathering additional evidence, with Haeberlein stating they will "continue to provide physicians with efficacy and safety data to help them make the best treatment decisions for patients as we learn from our ongoing trials and real-world evidence." The company's transparency in publishing these results marks an important step in the ongoing evaluation of Aduhelm's role in Alzheimer's treatment, though questions about its clinical utility and accessibility persist.
