Search for an Alzheimer’s Treatment Goes On

Anticipation was high for the results of a Phase 3 trial of Axovant’s experimental drug, interpirdine. Sadly, the potential Alzheimer’s disease treatment failed to meet its co-primary endpoints. Patients with mild to moderate Alzheimer’s disease who were treated for 24 weeks with 35 mg interpirdine, along with the existing Alzheimer’s disease drug Aricept, failed to show a statistically significant improvement in either cognitive ability or daily living activities compared to patients who received placebo plus Aricept. Interpirdine blocks the 5-HT6 receptor to help release the neurotransmitter acetylcholine, critical for thinking, while Aricept prevents acetylcholine breakdown; it was thought that the combination might improve cognition in patients with Alzheimer’s disease better than Aricept alone.

 

The next chance for a breakthrough in the search for an effective treatment for Alzheimer’s disease won’t come until 2019 or 2020, when data is expected from three large late-stage trials of drugs under development by Biogen, Merck, and partners Eli Lilly and AstraZeneca. All three focus on amyloid, one of the two protein hallmarks of Alzheimer’s disease — and also the focus of most previously failed drug candidates.

 

The Biogen candidate, aducanamab, is an antibody that targets toxic amyloid plaques deposited in the brain. In a small previous trial that we wrote about earlier this year, aducanamab showed signs that it could actually improve cognition.

 

The other two contenders both target an enzyme called BACE that is involved in the production of amyloid. Merck halted an earlier 2000-patient study of its drug candidate, verubecestat, after determining that it had “virtually no chance” of meeting its goals in patients with mild Alzheimer’s disease. The study to read out in 2019 is only enrolling patients in the earliest stages of the disease, in hopes of a better result.  The Lilly/AstraZeneca drug candidate, lanabecestat, is also enrolling patients with early Alzheimer’s disease.

 

Will we see a successful drug that intervenes by targeting amyloid production, deposition or toxicity in some way? Or are efforts better focused in new directions?  And will patients need to be treated before symptoms take hold to have an effect?  Please share your thoughts on our LinkedIn page!