Biogen and Eisai said Thursday that Phase III studies of the experimental anti-amyloid beta antibody aducanumab in patients with mild cognitive impairment due to Alzheimer's disease and mild Alzheimer's disease dementia will be halted as they are unlikely to meet their primary endpoints. "This disappointing news confirms the complexity of treating Alzheimer's disease," remarked Michel Vounatsos, CEO of Biogen, whose shares plunged up to 29 percent in reaction to the update.
Commenting on the news, RBC Capital Markets analyst Brian Abrahams said the development is a "transformative failure for Biogen's pipeline," while Guggenheim analyst Yatin Suneja called the outcome "investors' worst fears come true." Suneja added "while unfortunate, we are not particularly surprised as numerous AB-targeting compounds have failed to demonstrate benefit in Alzheimer's patients, and, in our view, this trial may signal the end of the current AB hypothesis of Alzheimer's aetiology."
Biogen and Eisai said that they will halt the late-stage ENGAGE and EMERGE trials on the recommendation of an independent data monitoring committee following a futility analysis, adding that the decision to stop the studies is not based on safety concerns. The primary objective of the trials was to evaluate the efficacy of monthly doses of aducanumab versus placebo in slowing cognitive and functional impairment as measured by changes in the Clinical Dementia Rating-Sum of Boxes score.
Meanwhile, the companies also indicated that the EVOLVE Phase II study and the long-term extension of the PRIME Phase Ib trial of aducanumab will be discontinued. Biogen and Eisai added that the initiation of a Phase III secondary prevention trial for aducanumab will be assessed while the data from ENGAGE and EMERGE are evaluated. Biogen licensed aducanumab, also known as BIIB037, from Neurimmune in 2007, with the company later inking a deal to co-develop the drug with Eisai.
Under the agreement, Biogen and Eisai are also developing the experimental anti-amyloid beta protofibril antibody BAN2401, with Vounatsos noting "we will continue advancing our pipeline of potential therapies in Alzheimer's disease." Eisai recently indicated that a Phase III confirmatory study of BAN2401 in early Alzheimer's disease patients would be initiated by the end of March after feedback from regulators in the US, EU and Japan suggested that a single trial would meet the requirements for approval.
However, Suneja suggested that Biogen should not pursue further development in Alzheimer's disease, and instead look at merger and acquisition opportunities for treatments targeting the central nervous system. "They need to stop wasting or stop investing money in Alzheimer's now," Suneja said, adding that potential takeover targets including GW Pharmaceuticals, Sage Therapeutics and Zogenix "should be considered now, more seriously." For further analysis, see ViewPoints: Aducanumab setback asks questions of Biogen's future strategy.
If successful, expectations for aducanumab had been high, with analysts at Goldman Sachs at one time forecasting that sales of the drug could reach $12 billion. "This was the largest opportunity and the most high-profile pipeline event for trial events in the entire space, you could argue, let alone for Biogen," remarked Jefferies analyst Jared Holz. "We've been talking about this for several years with an expectation we'd get a readout in 2020. There was obviously a chance you could have a futility analysis in 2019, but investors thought we were past that point," Holz added.
Holz commented that following the slump in Biogen's shares, "all you are left with now is a value stock – it's essentially Gilead [Sciences], a cheap stock with an unproven pipeline and a company that will be more reliant on M&A." SVB Leerink analyst Geoffrey Porges added "we cannot find any near term catalysts that would help [Biogen's] stock recover."
The failure of aducanumab adds to a growing list of drugs under development for Alzheimer's disease that have been ditched, particularly a number targeting amyloid beta. In January, Roche stopped two Phase III trials of crenezumab in patients with early sporadic Alzheimer's disease after a pre-planned interim analysis indicated that the studies of the anti-beta-amyloid molecule were unlikely to meet their primary endpoints.
For related analysis, see ViewPoints: Strike three – but the amyloid hypothesis ain't out.
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