ProMIS Neurosciences offers comments on recent FDA Advisory Committee meeting on aducanumab for the treatment of Alzheimer’s disease - Seite 2

Thus, on the first and most critical question to the committee, “Does Study 302, viewed independently and without regard for Study 301, provide strong evidence that supports effectiveness of aducanumab for the treatment of Alzheimer’s disease?”, the committee vote was negative, with 1 Yes, 8 No and 2 Uncertain. To a large degree, the other three questions assumed a Yes vote to the first question, including the last question as to whether Study 302 could be considered as primary evidence of effectiveness.

It is important to note that, prior to and during the advisory committee meeting, the FDA Office of Neuroscience made several key arguments supporting approval of aducanumab, as outlined below:

• Analysis of the data supporting the March 2019 decision to discontinue the trials because of futility did not provide “an accurate reflection of individual studies”. The futility decision was based on pooled data from both Study 301 and Study 302. However, if the two studies had been independently reviewed for futility, Study 302 would not have met the futility criteria and the magnitude of effect in the high-dose arm (10mg/kg) in fact improved over time as additional data were collected. FDA commented that it would have been more appropriate if futility had not been declared and noted that assumptions supporting the futility analysis had been violated.
• In response to Biogen’s argument that anti-amyloid beta (Aβ) antibodies differ considerably with respect to their molecular characteristics, FDA agreed that “anti-Aβ therapies do not represent a single class of drugs” and previous late-stage failures of such therapies “do not constitute a demonstrated ‘class failure’”. During committee discussion, this point was briefly noted as members acknowledged that a more nuanced discussion of oligomers as the most toxic molecular Aβ species was beyond the scope of the committee’s responsibility.

“Although FDA will most likely accept the non-binding recommendations of the advisory committee, it is disappointing for patients, their caregivers and the research community that the committee viewed the inconsistencies in data as too significant to reach a conclusion that aducanumab is clinically effective”, said Dr. James Kupiec, Chief Medical Officer for ProMIS Neurosciences. “We are however encouraged by FDA’s position on anti-Aβ antibodies. The amyloid hypothesis is far from dead now that the research community is focused on the most toxic molecular species, and we anticipate that PMN310, which selectively targets toxic Aβ oligomers, could demonstrate best-in-class effectiveness and safety in clinical studies”.