Early efficacy data from buntanetap trial delayed, now expected in June

Snags found in analysis process in trial of early-stage Parkinson’s therapy

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by Andrea Lobo |

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Topline efficacy data from a Phase 3 clinical trial evaluating the oral therapy buntanetap for early-stage Parkinson’s disease is now expected in June, Annovis Bio, the therapy’s developer, has disclosed.

While Annovis originally planned to share its early findings at the beginning of this year, the company faced a delay in the process of data cleaning: Specifically, after unraveling the patients who had received the experimental therapy versus the placebo during the data analysis process, researchers found more blood samples than expected showed no presence of buntanetap.

“We were expecting 33% blank samples from the placebo group, but we saw over 50% blank samples. We were afraid that we had mixed up bottles and that patients weren’t given what they were supposed to,” Maria Maccecchini, PhD, Annovis founder, president, and CEO, said in a company press release.

After searching for a possible explanation, the team found that the method used to assess buntanetap levels in patients’ samples had been modified, affecting the measurements.

“We repeated the [measurements] of the same samples and obtained an expected 33% of blank samples accounting for placebo,” Maccecchini said noting that “the whole process took us [two] months, which caused the delay in data announcement.”

Annovis is now “confident” in its assessments and “ready to evaluate the data for the public and [U.S. regulatory authorities] and report topline results in June,” Maccecchini said.

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Topline buntanetap trial data in early-stage Parkinson’s due ‘soon’

Over 450 patients completed Phase 3 trial testing buntanetap

Buntanetap, previously known as ANVS401 or posiphen, is designed to reduce the levels of proteins that accumulate into toxic clumps inside nerve cells, among them alpha-synuclein in Parkinson’s and beta-amyloid and tau in Alzheimer’s disease. This is achieved by blocking translation, the cellular process of producing proteins based on DNA instructions.

As such, the therapy is expected to improve synaptic transmission and axonal transport — key processes for the communication between nerve cells to transmit information — also thought to contribute to nerve cell degeneration and death, hallmarks of neurodegenerative diseases.

In this Phase 3 trial (NCT05357989), 523 early-stage Parkinson’s patients, ages 40-85, were randomly assigned to receive buntanetap, delivered as an oral capsule of either 10 or 20 mg, or a placebo, once daily for six months. The treatment was given in addition to each patient’s standard of care.

The study’s main goal is to assess the treatment’s safety and tolerability, as well as changes in parts II and III of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) scores. That scale evaluates activities of daily living and motor function.

Secondary goals include total MDS-UPDRS scores and Participant Global Impression of Change (PGIC), a measure of patients’ views of treatment efficacy.

A total of 471 patients across 67 clinical sites in the U.S. and Europe completed the study, according to the company, which noted that the dropout rate of 9.9% was lower than initial projections. Annovis believes this is the result of buntanetap’s safety profile and tolerability, and the convenience of taking just one pill a day.

In a previous Phase 1/2 trial (NCT04524351), buntanetap was found to be safe when given once daily for 25 days to people with early Parkinson’s or Alzheimer’s. The treatment also was found to improve cognitive and motor skills in Parkinson’s patients.

Moreover, results from this trial showed that use of this therapy significantly reduced the blood levels of TDP-43, another protein that can form toxic clumps inside nerve cells.

The company is planning a similar Phase 3 trial in people with late-stage Parkinson’s disease, for which the U.S. Food and Drug Administration (FDA) gave positive feedback in 2022, following the review of the Phase 2 trial efficacy data.

In announcing the “successful completion of data cleaning,” Annovis thanked all parties for their “understanding and patience.”