Investigators from the European Brain Research Institute (EBRI) recently presented data on an immunotherapeutic approach based on the monoclonal antibody (MAb) 12A12 for treating Alzheimer’s disease (AD).
In Alzheimer’s, the amyloid beta hypothesis has proved most persistent in terms of drug development efforts to date, but aggregation of other pathogenic factors – phosphorylated tau (p-tau), APOE4, TREM2 and alpha-synuclein, for example – have also emerged as hallmarks of the disease. It’s that aggregation that seven-year-old Truebinding Inc. aims to target with its lead program, TB-006, a monoclonal antibody against galectin-3.
Marking the latest Alzheimer’s disease (AD) disappointment, Eli Lilly and Co.’s solanezumab failed in a phase III trial to slow progression of cognitive decline in patients at the preclinical stage of the disease – those with amyloid plaque but no clinical symptoms – prompting the company to terminate development. The Indianapolis-based company is turning its attention instead to phase III AD products donanemab and remternetug.
The shadow of two reported patients’ deaths hovers over Eisai Co Ltd. and Biogen Inc.’s Alzheimer’s disease treatment, lecanemab, as the companies prepare to present phase III study data on the drug later today at the 15th Clinical Trials on Alzheimer's Disease conference.
Two phase III failures with Roche Holding AG subsidiary Genentech Inc.’s gantenerumab in staving off mild cognitive impairment tied to Alzheimer’s disease (AD) revealed the level of amyloid-beta removal was lower than the company expected. The protein amyloid beta accumulates in the brains of AD patients and its removal is suspected to be an eventual boon to AD patients. But there are still plenty of doubts. Top-line results from Genentech’s phase III Graduate I and II studies show gantenerumab, a fully human monoclonal IgG1 antibody, missed the primary endpoints of slowing clinical decline in those with mild cognitive impairment due to AD and mild AD dementia.
Extracellular vesicles (EVs) are nanosized membrane vesicles released from a variety of cells that play important roles in cell-cell communication and which circulate in almost every body fluid, including blood, urine and cerebrospinal fluid (CSF).
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.
