Btobioinnovation.com 

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

SPECIAL REPORT #22.10

More bad news for patients with Alzheimer’s disease.

On June 16, Roche reported that crenezumab, a beta amyloid monoclonal antibody, failed in the closely watched Phase II API-ADAD trial. Roche stated that only a small numerical advantage had been observed but nothing that qualified as a statistical beneficial outcome in preventing or slowing down cognitive decline. This flop follows two previous phase III failures CREAD 1 and CREAD 2 in 2019.

The API-ADAD study, which was backed by Genentech, the National Institute on Aging  (NIA), the Banner Alzheimer’s Foundation and the Neurosciences Group at the University of Antoquia in Columbia started in 2013, with 252 patients enrolled. The study aimed at showing positive preventive outcomes in Colombian families with autosomal dominant Alzheimer’s disease (ADAD) triggered by a Presenilin 1 E280A mutation. The University of Antioquia’s GNA Director and his team have identified 6,000 people across several families, of which 1,200 carry this specific mutation.  The randomised study in that high-risk population was followed for up to eight years and was expected to demonstrate that crenezumab could slow down the appearance of cognitive disabilities or episodic memory deficits. The trial missed the two primary endpoints as well as the secondary endpoints.

“We did not get the results we wanted. We learned that we could do such a study. We learned many things about this molecule that we are continuing to look at very closely and we learned that we can accomplish the goal of trying to prevent Alzheimer’s disease” said Rachelle Doody global head of Neurodegeneration at Genentech.

Richard Hodes, Director of the NIA also pointed at ideas different from the beta amyloid hypothesis for tackling the disease, including combination therapies – a proposal we have made since several years-  and other potential targets. The NIA is currently supporting 69 ongoing studies, of which 50% are amyloid-related and 50% are tackling other targets.

Roche is one of the very rare companies that have continued to invest and investigate drugs for Alzheimer’s disease. The company has still ongoing efforts for gantenerumab, another beta amyloid monoclonal antibody, with results from phase III clinical trials in more than 2,000 pateints expected for Q4 2022. Gantenerumab drug had earlier clinical failures.

This latest setback had a strong negative impact on AC Immune – the Swiss biotech which licensed the drug to Roche 16 years ag-  with a share plunge of 28% on the day of the announcement. Other biotechnology companies involved in the Alzheimer field such as Alector, Anavex Life Sciences, Cortexyme, INmune Bio and Prothena Corporation also saw a strong decline of their value.

Prevention trials are considered as the next best chance to help patients with Alzheimer’s disease. “Our best opportunity to intervene successfully has been to move to earlier stages before damage -potentially irreversible damage- has been done” said Richard Hodes.

Paris, June 17, 2022.

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