FDA Accepts Protocol for Annovis Bio’s Buntanetap Phase 3 Alzheimer Disease Trial
Buntanetap is an oral molecule designed to inhibit the production of multiple neurotoxic proteins and is under investigation for treatment of Alzheimer Disease, Parkinson’s Disease, and other neurodegenerative diseases.
Kore Liow, MD, FAFP, FAAN
Credit: Hawaii Pacific Neurology
The US Food and Drug Administration (FDA) has accepted a revised protocol for Annovis Bio Inc’s pivotal phase 3 study of buntanetap in Alzheimer disease (AD), according to a company news release.
Under the new protocol, two studies are now integrated into a single trial, which will include a 6-month data readout focused on symptomatic effects, followed by an additional 12-month assessment to evaluate the disease-modifying potential of buntanetap. This approach will allow for a 6-month interim data analysis to potentially support a New Drug Application (NDA) while the same cohort continues for a longer-term outcome assessment, according to Maria Maccecchini, PhD, Founder, President, and CEO of Annovis Bio.
“This consolidated protocol will accelerate the development timeline while maintaining the scientific rigor necessary to advance buntanetap as a treatment for AD,” Maccecchini said in a news release. “We are excited to move forward with this approach, which brings us closer to delivering a novel treatment to patients in need.”
Under the new protocol, investigators will capture short-term symptomatic data during the first 6 months and maintain the same participant group for an additional 12-month phase to evaluate disease-modifying potential. These combined studies replace an earlier plan for two separate trials.
Buntanetap is an oral molecule designed to inhibit the production of multiple neurotoxic proteins — including amyloid β, tau, α-synuclein, and TDP43 — aiming to restore synaptic function and attenuate neuroinflammation. The drug is under investigation for potential symptomatic and disease-modifying benefits in AD, Parkinson’s Disease (PD), and other neurodegenerative diseases.
The FDA cleared the company in October 2024 to proceed with phase 3 research following positive phase 2/3 findings announced in April 2024 that demonstrated cognitive improvement in patients with early-stage AD.
The randomized, double-blind, placebo-controlled trial (NCT05686044) enrolled more than 300 participants, all receiving either placebo or one of three doses of buntanetap once daily for 12 weeks. According to the company, buntanetap produced a 3.3-point average improvement on the Alzheimer’s Disease Assessment Scale–Cognitive Subscale 11 (ADAS-Cog 11) in a biomarker-confirmed early AD subgroup.
“These findings are a significant milestone for Alzheimer's patients,” said Kore Liow, MD, Director, Memory Disorders Center, Alzheimer's Research Unit, Clinical Professor of Neurology, University Hawaii, and principal investigator on the AD and PD trials, in a April 2024 news release. “Buntanetap has the potential to be the first safe and convenient oral therapy that provides symptomatic efficacy while slowing disease progression. The mechanistic pathway and science are novel, and our physicians and researchers at the Hawaii Memory Center & Alzheimer's Research Unit are proud to have contributed to four studies and look forward to participating in future studies.”
As for investigations into the drug for treatment of PD, the company reported new findings from a phase 3 study highlighting statistically significant improvements in both motor and cognitive symptoms in patients, including those with postural instability and gait difficulties.
References
- FDA Accepts Final Protocol for Pivotal Phase 3 Alzheimer’s Disease Study, Streamlining Development Pathway [press release]. Published January 7, 2025. Accessed January 9, 2025. https://www.annovisbio.com/press-release/fda-accepts-final-protocol-for-pivotal-phase-3-alzheimers-disease-study-streamlining-development-pathway
- Annovis Bio Announces Statistically Significant Phase II/III Data in Patients With Early Alzheimer’s Disease [press release]. Published April 29, 2024. Accessed January 9, 2025. https://www.annovisbio.com/press-release/annovis-bio-announces-statistically-significant-phase-ii-iii-data-in-patients-with-early-alzheimers-disease
- Annovis Bio Announces New Data from Phase III Parkinson’s Study Highlighting Improvements in Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Cognition After Treatment With Buntanetap [press release]. Published July 2, 2024. Accessed January 9, 2025. https://www.annovisbio.com/press-release/annovis-bio-announces-new-data-from-phase-iii-parkinsons-study-highlighting-improvements-in-unified-parkinsons-disease-rating-scale-mds-updrs-and-cognition-after-treatment-with-buntanetap
