Eisai and Biogen announced that a final analysis of a Phase II study showed that the highest dose of the experimental anti-amyloid beta protofibril antibody BAN2401 significantly slowed clinical decline versus placebo and reduced amyloid beta in the brain in patients with early Alzheimer's disease. Lynn Kramer, chief clinical officer and chief medical officer at Eisai's neurology business group, said "we will discuss these very encouraging results with regulatory authorities to determine the best path forward."
In Study 201, 856 patients with mild cognitive impairment due to Alzheimer's disease, or mild Alzheimer's dementia with confirmed amyloid pathology in the brain, were randomised to receive one of five dose regimens of BAN2401 or placebo. The companies noted that efficacy in the trial was evaluated at 18 months using Eisai's in-house developed Alzheimer's disease Composite Score (ADCOMS), which combines items from the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog), the Clinical Dementia Rating Sum of Boxes (CDR-SB) scale and the Mini-Mental State Examination (MMSE).
In December last year, Eisai and Biogen reported that an independent data monitoring committee determined that BAN2401 "did not meet the criteria for success" based on an analysis for the primary endpoint at 12 months. At the time, the companies explained that the trial design allowed "for automatic changes...including adaptively changing the subject allocation ratio to treatment arms with higher probabilities based on the results of interim analyses." The drugmakers noted that the interim look at the data, which was based on a Bayesian analysis, was designed to enable a faster entry into Phase III development, while the final assessment at 18 months used a predefined conventional statistical method.
Top-line results showed that at 18 months, the highest dose of BAN2401 achieved significance on the key predefined endpoints of slowing progression in ADCOMS and on reduction of amyloid accumulated in the brain as measured using amyloid-PET. Eisai and Biogen added that the highest dose of BAN2401 began to show significant clinical benefit as measured by ADCOMS as early as six months, including at 12 months. The drugmakers also noted that dose-dependent changes from baseline were observed across the PET results and the clinical endpoints.
According to Eisai and Biogen, BAN2401 demonstrated an acceptable tolerability profile through 18 months, with the most common treatment-emergent adverse events being infusion-related reactions and amyloid-related imaging abnormalities (ARIA). Results showed that infusion related reactions were mostly mild-to-moderate in severity, while the incidence of ARIA oedema was not more than 10 percent in any of the treatment arms, and less than 15 percent in patients with APOE4 at the highest dose. Detailed results from the study will be presented at a future medical meeting.
"This is the first late-stage anti-amyloid antibody study to successfully achieve statistically significant results at 18 months, further validating the amyloid hypothesis," Kramer remarked. Meanwhile, Alfred Sandrock, chief medical officer at Biogen, commented "the prospect of being able to offer meaningful disease-modifying therapies to individuals suffering from this terrible disease is both exciting and humbling."
Jefferies analysts including Michael Yee noted that the study outcome was a "best case" scenario, given that expectations were low following the interim analysis, with the news sending shares in Eisai up nearly as much as 19 percent, while Biogen's stock climbed 15 percent. However, Bloomberg Intelligence analyst Sam Fazeli said the success of BAN2401 will depend on the details of the data. "The question is, is it real?" Fazeli remarked, adding "when we see the data, will the room be filled with oohs and aahs, or will the room say, 'oh my god, not again?'"
Eisai licensed exclusive global rights to BAN2401 from BioArctic in 2007, and has been jointly developing the drug with Biogen under the terms of a 2014 agreement focused on treatments for Alzheimer's disease. Earlier this year, Eisai also exercised its option to jointly develop and promote Biogen's investigational anti-amyloid beta antibody aducanumab.
Late-stage studies of aducanumab are ongoing, with Biogen announcing earlier this year that it was increasing patient enrolment in a Phase III trial of the therapy after observing greater-than-expected variability regarding the primary endpoint. "We have two drugs either of which could be the very first disease-modifying therapy for Alzheimer's," said Sandrock, adding "to see it once is one thing, but to see it again with a very different antibody is like repeating the experiment twice and seeing the same result."
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