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Author: Jean-Claude Muller, 穆卓Executive Editor at BtoBioInnovation  jcm9144@gmail.com

SPECIAL REPORT #37

Novo Nordisk and AB Science disclose preliminary positive results in the treatment of Alzheimer’s disease

Over the last months we have mainly published on COVID-19 treatments and outcomes. Earlier this week important and unexpected results were disclosed related to the treatment of Alzheimer’s disease which were not highly publicised.

On Wednesday December 16, Novo Nordisk announced its decision to initiate a phase 3 trial with semaglutide in Alzheimer’s disease. The programme which is planned to start in H1 2021, will involve 3,700 patients and aims at investigating the efficacy and safety of a 14 mg once a day dosis, of oral semaglutide compared to placebo over a period of 24 months, with potential interim analyses. Semaglutide, is a long acting GLP-1 (glucagon-like peptide 1) analogue, already approved in Europe, Japan and the United States for the treatment of type-2 diabetes.

On the same day, AB Science (located in Paris) announced that the phase 2b/3 study evaluating two dose regimens of oral masitinib, in patients with mild to moderate Alzheimer’s disease, met its primary end-points. The study which included 720  patients  demonstrated that masitinib at 4.5 mg/kg/day generated significant treatment effects in the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) as well as in the Alzheimer’s Disease Cooperative Study of Daily Living (ADCS-ADL), when compared to an add-on therapy to a cholinesterase inhibitor or memantine. “The preliminary results from this study support efficacy on important outcomes assessing both cognition and function. The observed patient tolerability is encouraging. Masitinib’s mechanism is novel in its targeting of the innate immune system via mast cells and microglia. A growing body of evidence suggests that microglia play a central role in Alzheimer’s disease and other neurodegenerative disorders.” said Jeffrey L. Cummings, M.D., Director of the Chamber-Grundy Center for Transformative Neuroscience at UNLV in Las Vegas, one of the study investigator. Masitinib is an inhibitor acting on c-Kit, Lyn and Fyn kinases, which target mast cells, and a potent inhibitor of MCSFR-1  kinase that targets macrophages and microglia. Masitinib has already been evaluated in a large setting of human and veterinary clinical indications including oncology, diseases of the central nervous systems and most recently against COVID-19.

On December 15, vTv Therapeutics (High Point, North Carolina, USA) disclosed that azeliragon (TTP488) failed to improve cognition in a trial with mild Alzheimer’s and type 2 diabetes. The 21 patients treated during 6 months with azeliragon declined on the ADAS-Cog14 score (14 items analysed) dropping from 1.8 points compared to 0.35 points in the placebo group. Azerilagon is an orally bioavailable small-molecule acting as an antagonist of RAGE (Receptor for Advanced Glycation Endproducts).

The results released by Novo and AB Science are interesting in so far that they are not directly tackling the beta-amyloid pathway which has been associated with so many recent late-stage clinical studies failures. It now remains to be seen  what type of phase 3 clinical protocols will be requested by various health authorities. Final clinical outcomes for the both drugs should not be available before the end of 2024 at the very best.

Last Minute News

The 163rd Vaccine and Related Biological Products Advisory Committee (VRBPAC) overwhelmingly voted, 20 yes, 0 no and 1 abstention, that the benefits of Moderna’s mRNA-1273, its COVID-19 vaccine, outweighs its risks. The U.S. FDA will probably issue an Emergency Use Authorisation (EUA) for the vaccine within the next hours paving the way for a second COVID-19 vaccine to be approved in the United States.

Paris, December 17, 2020

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