Despite a disastrous commercial rollout, Biogen is still producing longer-term data for beleaguered Alzheimer’s disease therapy Aduhelm.
In patients who’ve been treated with Aduhelm for up to two and a half years, Aduhelm continued to lower the levels of amyloid beta plaques in the brain and blood levels of the p-tau181 protein, Biogen said at the International Conference on Alzheimer’s and Parkinson’s Diseases.
The data come from patients in two phase 3 trials who participated in a long-term extension phase. Biogen previously used data from the phase 3 trials to score an accelerated FDA approval for the drug in June 2021. Full data from the two studies have just been published in The Journal of Prevention of Alzheimer’s Disease.
Amyloid beta and p-tau are biomarkers invovled in Alzheimer’s disease. As it has done before, Biogen teed up a potential link to clinical benefits from Aduhelm.
Specifically, at week 78, patients who enjoyed a reduction in plasma p-tau181 had slower clinical progression across all four measurements of cognition and function in both phase 3 trials, Biogen said.
In addition, patients who met a criteria of wider amyloid beta reduction at week 78 had greater decreases in p-tau181 at week 128.
“These data demonstrate that long-term treatment with Aduhelm continues to reduce the underlying pathologies of Alzheimer’s disease beyond two years," Biogen said Wednesday.
Aduhelm is designed to target amyloid beta, and questions have continuously circled around whether amyloid-lowering drugs can improve clinical outcomes. With the latest data, Biogen is basically arguing that by reducing amyloid beta, Aduhelm could also lower soluble p-tau, and that could affect the downstream pathology of Alzheimer’s, leading to slower cognitive decline.
Critics argue that the drug hasn't shown a definitive benefit for patients, so the FDA shouldn't have approved the medicine for a commercial rollout.
When Biogen revealed the first p-tau data in November, the correlation between soluble p-tau181 and cognition was weak, with correlation values ranging between positive or negative 0.11 to 0.21 in the two trials.
In addition to questions about efficacy, Aduhelm is also facing serious concerns about safety, specifically a potentially fatal side effect called amyloid-related imaging abnormalities. Several patients’ deaths after treatment with Aduhelm have been reported to the FDA’s adverse event reporting system, or FAERS. Biogen and FDA have launched investigations into whether the deaths were related to Aduhelm.
Just as it accrues data from existing trials, Biogen is prepping for a new randomized clinical trial dubbed Envision to serve as Aduhelm’s confirmatory study. For that trial, the company is hoping to screen its first patient in May.
Meanwhile, Biogen is also collecting real-world data from a single-arm phase 4 study dubbed ICARE AD-US.
In recent draft guidance, the Centers for Medicare & Medicaid Services is proposing to restrict Aduhelm’s coverage on Medicare to patients enrolled in a randomized clinical trial. The agency is expected to make a final policy next month.