Annovis Highlights Subgroup Success in Buntanetap Parkinson's Trial

Annovis Bio has recently unveiled data from a Phase III study of buntanetap (posiphen/ANVS401), aimed at treating early-stage Parkinson's disease. The study focused on subgroup analyses and left some uncertainty regarding the drug's performance on its primary endpoint. Initially expected in January, the readout was delayed due to what the company termed "necessary cleaning efforts required to deliver reliable and accurate results."

The clinical trial involved 523 early Parkinson's patients who were administered either 10mg or 20mg of buntanetap daily for six months, with a control group receiving a placebo. Buntanetap is designed to inhibit the formation of neurotoxic proteins such as amyloid beta, tau, alpha-synuclein, and TDP43. The primary endpoint of the study was the change in motor experiences of daily living, measured using the MDS-UPDRS Part II scale, from baseline to six months.

Initially, the primary endpoint was set to be MDS-UPDRS Part II+III. However, following feedback from the FDA, the company chose to focus solely on Part II, considering it more relevant for detecting clinically significant changes. Consequently, MDS-UPDRS Part III was reassigned as a secondary outcome measure.

Annovis described evaluating the drug's impact on the primary endpoint as "challenging," primarily because patients diagnosed with Parkinson's less than three years ago showed "minimal or no deficits in MDS-UPDRS Part II." Despite this, in a subgroup of patients diagnosed more than three years ago, significant improvements were observed in MDS-UPDRS Part II, Part III, and combined Part II+III scores for the 20mg dose of buntanetap compared to placebo and baseline.

In another subgroup analysis, patients with postural instability and gait difficulty (PIGD)—a subset known for faster disease progression—demonstrated "significant improvements" across MDS-UPDRS Part II, Part III, combined Part II-III, and total scores.

The company also noted cognitive benefits in an exploratory analysis, although cognition was not listed among the study's secondary endpoints. Most patients had normal cognitive functioning, but 12% experienced cognitive decline as assessed by the Mini-Mental State Examination (MMSE). According to Annovis, those in the placebo group declined by 1.5 MMSE points. Among patients with mild dementia, the 10mg dose of buntanetap slowed cognitive decline, while the 20mg dose resulted in a "significant improvement in cognition" compared to the placebo. Parkinson's patients with significant cognitive decline showed "very pronounced" improvement.

Investor sentiment appeared positive following the readout. Although the company's shares opened the day about 9% lower, they surged over 101% by early afternoon trading. Annovis drew parallels between these results and their Alzheimer's disease study, where buntanetap also showed statistically significant cognitive improvements in patients with MMSE scores above 20. In April, the company announced Phase II/III success in Alzheimer's disease, despite some issues in patient screening and missing a co-primary endpoint, which had previously caused a significant drop in shares and raised doubts about the drug's efficacy. However, Annovis stated that they would proceed with pivotal testing and discuss the trial outcomes with the FDA.

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