- Biogen and Eisai on Friday announced they would stop two studies of the experimental Alzheimer's disease drug elenbecestat because the trials' data monitoring board found evidence of an "unfavorable risk-benefit ratio" in a safety review.
- It is the second time the partners have called an early halt to testing of an Alzheimer's drug this year. Phase 3 trials of aducanumab were discontinued in March after study monitors determined that the anti-amyloid agent wouldn't slow patients' cognitive decline.
- Elenbecestat's failure is yet another blow to the once-leading hypothesis in Alzheimer's disease, that accumulation of a protein called beta amyloid in the brain leads to cognitive decline. In this case, the drug targets beta secretase, an enzyme believed to lead to elevated beta amyloid levels.
Cessation of the MISSION AD1 and 2 trials are almost anticlimactic, given how far faith in the beta amyloid hypothesis has declined this year. Aducanumab's failure in March was a pivotal moment, as it led to a $17 billion decline in Biogen's valuation, while the biotech's shares rose slightly on Friday following the elenbecestat announcement.
Prior to Biogen ending the ENGAGE and EMERGE trials, aducanumab was one of the few beta-amyloid targeting monoclonal antibodies that hadn't yet had a late-stage failure. Elenbecestat held a similar position in its class, called BACE inhibitors.
Over the past 16 months, Johnson & Johnson stopped work on its BACE blocker atabecestat, and this summer Amgen and Novartis called time on umibecestat. Different reasons were given, with atabecestat treatment resulting in elevated liver enzymes and umibecestat leading to a worsening in some measures of cognitive function.
Biogen and Eisai did not cite the reason for stopping the MISSION AD program other than the noting that the decision came following a safety review. More details will be disclosed at an upcoming medical meeting, the companies said.
"In our view, the discontinuation of elenbecestat is mostly a relief for Biogen investors as a step to unwind their investment in beta amyloid programs," wrote SVB Leerink analyst Geoffrey Porges in a September 13 note to clients.
The two companies still have an active collaboration on another beta-amyloid binding antibody, called BAN2401. That experimental drug is in a Phase 3 trial called Clarity AD, which, if it continues to its conclusion, will have results in 2022.
If results read out on schedule, they will arrive a decade after the first big sign the amyloid hypothesis might not be a successful approach to slowing Alzheimer's progression: failure of the beta-amyloid binding antibody bapineuzumab, which was in trials sponsored by Johnson & Johnson, Pfizer and Elan.
Beta amyloid-binding antibodies like Eli Lilly's solanezumab are still in university-sponsored trials that aim to prevent development of Alzheimer's in people genetically pre-disposed to the disease, however.