Eisai announced Friday that a Phase III trial has been initiated for the anti-amyloid beta protofibril antibody BAN2401, which is partnered with Biogen, for use in patients with early Alzheimer's disease. The news follows the companies' recent announcement to discontinue late-stage testing for the anti-amyloid beta antibody aducanumab in early Alzheimer's disease, saying the studies were unlikely to meet their primary endpoints. 

The new Clarity AD trial will involve 1566 patients with mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's disease dementia with confirmed amyloid accumulation. Participants will be randomly assigned to treatment with BAN2401 bi-weekly or placebo. The primary endpoint is change versus baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) scale at 18 months, while key secondary goals include respective changes from baseline to 18 months in the AD composite score (ADCOMS), AD Assessment Scale–Cognitive Subscale (ADAS-cog), and brain amyloid levels as measured by amyloid positron emission tomography. According to Eisai, final readout of the primary endpoint is targeted for 2022. 

The Japanese drugmaker disclosed last month that a late-stage study of BAN2401 would likely be initiated by the end of March after regulators had indicated that a single study could be sufficient for approval. Mid-stage study data unveiled last year illustrated that the treatment had significantly slowed clinical decline versus placebo and reduced amyloid beta in the brains of patients with early Alzheimer's disease.

Eisai, which gained exclusive global rights to BAN2401 from BioArctic in 2007, entered into a partnership with Biogen in 2014 targeting treatments for Alzheimer's disease, including BAN2401. BioArctic noted that it will receive a milestone payment when the first patient is dosed in the Clarity AD study. 

A spokesman for Eisai said "we still believe that the amyloid beta hypothesis is potentially the right approach for the treatment of Alzheimer's disease." However, SVB Leerink analyst Geoffrey Porges declared that theory "dead," and called on Biogen to take "the responsible decision to terminate all further investments in beta amyloid-directed medicines," which he described as "a complete waste of capital." The analyst, who also expressed concerns about the future of the company's multiple sclerosis and spinal muscular atrophy franchises, added that "if Biogen does not make this decision, then our adjusted expense forecast could be too low, with further negative effects on our valuation." Porges predicted "the next few months are likely to consist of a mixture of recriminations, explanations, negotiations and possibly terminations and litigation," adding that he expects Biogen to explore asset sales and purchases.

Meanwhile, UBS analyst Carter Gould urged Biogen to seek a merger to expand its pipeline. "Investor focus on Biogen escalating its [mergers and acquisitions] pace is likely only to intensify," he said, noting that "the company's conservative and patient approach to the topic will likely be tested."

Earlier this year, Roche terminated two Phase III studies of its anti-beta-amyloid candidate crenezumab in patients with early sporadic Alzheimer's disease after an interim analysis indicated that the primary endpoints would likely be missed. Prior to that, Eli Lilly and AstraZeneca had ended a late-stage study of the BACE inhibitor lanabecestat in Alzheimer's disease after an independent Data Monitoring Committee said the trial would probably fail. 

For related analysis, see ViewPoints: Aducanumab setback asks questions of Biogen's future strategy. See also ViewPoints: Strike three – but the amyloid hypothesis ain't out.

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