Researchers at the University of Cincinnati have published data showing that in patients with dominantly inherited Alzheimer’s disease (AD)-causing mutations, high levels of soluble amyloid-β42 (Aβ42) in the cerebrospinal fluid (CSF) predicted a reduced risk of developing dementia over 3 years. Their work, which appeared in the Oct. 4, 2022, print issue of the Journal of Alzheimer’s Disease after earlier publication online, suggests that the problem with amyloid in AD may be a lack of soluble amyloid-β, rather than a surfeit of plaques.
As therapeutics development in Alzheimer’s disease (AD) is broadening its search for therapeutic targets, one of the alternatives to amyloid-β, or at least to its direct targeting by monoclonal antibodies, that is coming into focus is triggering receptor expressed on myeloid cells 2 (TREM2). From a drug development standpoint, amyloid-β remains a mystery. Scientific evidence clearly suggests that amyloid misprocessing is an underlying factor in the development of AD, and it is certainly a reasonable hypothesis that reducing amyloid plaque should fight the disease.
The release by the U.S. CMS of the final national coverage determination (NCD) for Biogen Inc.’s Alzheimer disease (AD) drug, Aduhelm (aducanumab), lit speculation on the meaning for others in the space. CMS is “still being conservative,” said Howard Fillit, co-founder and chief science officer of the Alzheimer’s Drug Discovery Foundation (ADDF). “We’re in a new era. It’s unprecedented that Medicare doesn’t pay for a drug that received approval from the FDA,” even though it was not a full but an accelerated clearance.
The U.S. Center for Medicare & Medicaid Services (CMS) opened a 30-day comment window on its proposed national coverage determination (NCD) to limit Medicare access to monoclonal antibodies targeting amyloid beta in Alzheimer’s disease (AD) only in clinical trials. Biogen Inc., clearly the target, along with its AD treatment Aduhelm (aducanumab), was among the first to respond.
Investors were thrilled when Roche Holding AG subsidiary Genentech Inc. and AC Immune SA reported top-line results from the Lauriet trial on Aug. 31, giving a positive jolt to AC Immune’s stock on the day of the announcement. At the Clinical Trials in Alzheimer’s Disease 2021 meeting, the reaction of the medical community was more skeptical.
Just months after the controversial FDA approval of Alzheimer’s disease drug Aduhelm (aducanumab), partners on that medicine, Eisai Co. Ltd. and Biogen Inc., are advancing a BLA for another possible AD therapy, lecanemab. Formerly known as BAN-2401, the Bioarctic AB-originated antibody is designed to neutralize and eliminate soluble, toxic amyloid beta for the treatment of early AD. The rolling submission, in pursuit of an accelerated approval, was primarily based on data from a phase IIb trial in people with early AD and confirmed amyloid pathology.
A sometimes contentious policy roundtable on how to handle Alzheimer’s disease therapies followed the July 15 meeting of the California Technology Assessment Forum, an independent evidence appraisal committee of the Institute for Clinical and Economic Review (ICER). CTAF’s 15 panelists voted unanimously that the evidence was not adequate to prove Biogen Inc.’s recently approved Aduhelm (aducanumab) superior to supportive care alone.
Members of the California Technology Assessment Forum (CTAF), an independent appraisal committee of the Institute for Clinical and Economic Review (ICER), discussed – and voted on – the safety vs. efficacy and other aspects of Biogen Inc.’s embattled Aduhelm (aducanumab), the amyloid beta-targeting therapy recently approved for Alzheimer’s disease. It didn’t go well for Biogen.
New FDA breakthrough therapy designations awarded for two investigational Alzheimer's disease (AD) candidates, Eli Lilly and Co.'s donanemab and the Bioarctic AB-Eisai Co. Ltd.-developed asset lecanemab (BAN-2401) underline ongoing willingness at the U.S. regulator to invest deeper attention in the potential of amyloid plaque reduction to slow progress of the disease, a critical and costly challenge estimated to affect more than 6 million Americans.
Alzheimer’s disease can be divided into multiple subtypes based on gene expression patterns, investigators at the Mount Sinai School of Medicine reported in the Jan. 6, 2021, issue of Science Advances. The work, corresponding author Bin Zhang told BioWorld, is “the first major finding of subtypes in Alzheimer’s disease.”
