Phase 2/3 trial results for oral buntanetap expected in March 2024
Buntanetap also being tested in early Parkinson's patients in Phase 3 trial
An ongoing Phase 2/3 clinical trial testing Annovis Bio’s treatment candidate buntanetap in people with Alzheimer’s disease is expected to be fully enrolled next month, with trial data anticipated in March 2024, according to a company update.
These estimations come after a recent six-week interim analysis of 107 trial participants indicated that the placebo-controlled study should continue as planned with its original enrollment target of 320 adults, ages 55-85, with mild-to-moderate Alzheimer’s.
Independent analysis conducted for blinded clinical trial
To prevent bias, Annovis, trial investigators, and participants will not know which patients received buntanetap and which were on a placebo until after the trial is finished. For that reason, the analysis was conducted by an independent statistical group not directly involved in the study.
While the analysis indicates that based on available data, 320 participants should still be enough to detect a significant effect of buntanetap on the trial’s main efficacy goals, Annovis is encouraged by the results.
In general, the stronger the effects of a treatment, the fewer participants needed to be able to detect its benefits.
“Sample size re-estimation for the study is not necessary, which in our view, may signal an emerging positive treatment effect in patients receiving buntanetap versus those receiving placebo after just 6 weeks of treatment,” Maria L. Maccecchini, PhD, founder, president, and CEO of Annovis, said in a company press release.
“While the interim analysis does not mean that the trial will necessarily be successful, it does mean that the trial is powered for potential success.”
To date, 230 patients have been enrolled in the Phase 2/3 trial (NCT05686044), 62 of whom have completed the study. Recruitment is ongoing at more than five dozen sites in the U.S. Annovis expects all participants to have completed treatment in February.
Results from an interim safety analysis, to be conducted by a data and safety monitoring board on Oct. 18, will also be released in the next couple of weeks.
Buntanetap, previously known as ANVS401 or posiphen, is designed to lower levels of toxic protein clumps that accumulate and disrupt nerve cell function in people with neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease. In Alzheimer’s, these toxic clumps are made of the amyloid-beta and tau proteins.
The treatment prevents the production of these toxic proteins by blocking their translation, or the process by which genetic information is read to produce a working protein.
In a previous Phase 2a trial (NCT04524351), daily treatment with oral buntanetap (80 mg) for 25 days significantly reduced amyloid-beta and tau levels and improved cognition relative to a placebo among adults with early Alzheimer’s. Benefits were also observed in a group of Parkinson’s patients who participated in the trial.
Participants randomly assigned to 1 of 3 buntanetap doses or placebo
In the ongoing Phase 2/3 trial, adults with mild to moderate Alzheimer’s are being randomly assigned to receive either one of three doses of buntanetap (7.5, 15, or 30 mg) or a placebo, once daily for 12 weeks (about three months).
One of the study’s main goals is to assess changes in cognitive function, as assessed by the Alzheimer’s Disease Assessment Scale – Cognitive Subscale 11. The other is to assess clinicians’ perceptions of the daily functioning of their patients, as assessed by the Alzheimer’s Disease Cooperative Study – Clinical Global Impression of Change.
Secondary goals include changes in other cognitive tests and in caregiver-rated activities of daily living.
Buntanetap is also currently being tested in early Parkinson’s patients within a Phase 3 trial that’s expected to end next month.
In addition, Annovis is developing a new crystalized formulation of buntanetap called ANVS402, with plans to transition from buntanetap to ANVS402 in the clinical pipeline after discussions with U.S. regulators. Bridging studies to support this transition are expected to finish early next year.