Buntanetap linked to improved cognition, tau reduction in phase 2/3 study

In a phase 2/3 clinical trial, treatment with buntanetap was linked to cognitive gains as well as tau reduction at 12 weeks in those exhibiting mild to moderate symptoms of Alzheimer’s disease, according to the drug’s manufacturer.

In a press release, Annovis Bio stated that the United States-based study — which was reviewed by the Data and Safety Monitoring Board in October 2023 and given the go-ahead to proceed as planned — is a randomized, double-blind, placebo-controlled trial investigating safety, efficacy and tolerability of the oral, small molecule neurotoxic protein inhibitor across three distinct doses.

A total of 353 individuals with mild to moderate AD whose Mini Mental State Examination (MMSE) scores at baseline ranged from 14 to 24. Patients received either 7.5 mg, 15 mg, 30 mg buntanetap or placebo as an adjunct to standard care for 12 weeks. The trial’s two main endpoints were change in Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11) and Alzheimer’s Disease Cooperative Study Clinician’s Global Impression of Change (ADCS-CGIC), which assess cognition and activities of daily living.

At week 12, ADAS-Cog 11 scores showed a statistically significant improvement across all three doses, as well as when doses were combined, compared with those given placebo. Additionally, total tau levels were decreased across all three buntanetap doses, while the drug was generally safe and well tolerated with mild to moderate adverse events recorded.

The efficacy endpoint with respect to ADCS-CGIC was not attained because of the short trial duration.

“Based on buntanetap’s unique mechanism of action, we believe it can give patients both symptomatic and disease-modifying benefits,” Melissa Gaines, senior vice president clinical operations at Annovis and Cheng Fang, PhD, senior vice president research and development, stated in the release. “It’s really exciting to see that this study confirmed what we have observed in the previous phase 2 studies in both the improvement of patients’ cognition and the improvement of biomarkers.”

Based on these data, Annovis stated plans to commence a phase 3 trial in biomarker-positive early AD patients.