Buntanetap found to halt cognitive decline in early Parkinson’s trial

Daily treatment also improved motor function in patients, new data show

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by Steve Bryson, PhD |

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Two hands, a stethoscope, and a handful of oral medications surround a graph labeled 'CLINICAL TRIAL' and showing positively-trending results.

Six months of once-daily buntanetap halted cognitive decline among people in the early stages of Parkinson’s disease, and improved cognition in those with mild dementia.

That’s according to new data from a Phase 3 trial (NCT05357989), which showed that the therapy candidate, developed by Annovis Bio, also improved motor function in patients with a diagnosis more than three years prior, as well as in those with postural instability and gait difficulties.

“We are very pleased to see improvements in many of our patients over such a short course of treatment,” Maria Maccecchini, PhD, founder, president, and CEO of Annovis Bio, said in a company press release.

Previously known as ANVS401 or posiphen, buntanetap is an oral therapy designed to suppress the production of proteins that form toxic clumps in neurodegenerative diseases — specifically alpha-synuclein in Parkinson’s disease and beta-amyloid and tau in Alzheimer’s disease.

The company stated that these “new data … [demonstrate] that buntanetap is safe and effective in improving motor and non-motor activities and improving cognitive functions in patients with early Parkinson’s disease.”

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Phase 3 trial of buntanetap enrolled over 500 early-stage Parkinson’s patients

Data from a previous Phase 1/2 trial (NCT04524351) supported the launch of the Phase 3 study. That earlier trial showed that buntanetap safely outperformed a placebo in improving cognitive and motor skills in Parkinson’s. Overall disease severity was lessened, as indicated by scores on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS).

Treatment also lowered blood levels of TDP-43, a protein that builds up into toxic clumps, similar to alpha-synuclein, in Parkinson’s.

The Phase 3 study enrolled 523 patients, ages 40-85, with early-stage Parkinson’s. Participants were randomly assigned to receive buntanetap, administered as an oral capsule of either 10 or 20 mg, or a placebo, once a day for six months. Eligible patients included those with mild dementia, as indicated by the Mini-Mental State Examination (MMSE).

The study’s primary goals included the treatment’s safety and tolerability, as well as changes in part II of the MDS-UPDRS, which assessed the motor experiences of daily living. Secondary measures included MDS-UPDR part III for motor function and total MDS-UPDRS scores.

As an exploratory outcome, MMSE scores for cognitive function were assessed at enrollment and again at the end of the study. A total of 12% of participants showed cognitive impairment before the study, as indicated by MMSE scores between 20 and 26.

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Treatment also found to slow cognitive decline in patients with mild dementia

According to the newly released data, patients who received either dose of buntanetap maintained cognitive abilities. In contrast, those given the placebo continued to decline throughout the study, “indicating a statistically significant effect of the drug in stopping cognitive decline,” the company stated in its release.

Among patients with mild dementia, cognition deteriorated more slowly in those given the 10 mg dose than it did among those in the placebo group. Moreover, treatment with the 20 mg dose significantly outperformed the placebo in slowing cognitive decline.

Patients diagnosed less than three years before the study showed minimal or no deficits in MDS-UPDRS Part II, which made it challenging to measure treatment efficacy over six months, the company noted.

However, in patients diagnosed with Parkinson’s for longer than three years, 20 mg of buntanetap significantly improved MDS-UPDRS Part II scores over the placebo. Total MDS-UPDRS scores, and those for part III, and part II plus part III, also significantly improved with treatment versus the placebo in these patients.

Significant improvements across all MDS-UPDRS assessments were noted among patients with postural instability and gait difficulties — a group known to progress faster than other Parkinson’s patients without these problems.

These compelling data reinforce our commitment to advancing buntanetap into a longer study, which will allow us not only to verify observed symptomatic improvements but also to explore buntanetap’s disease-modifying properties.

Buntanetap maintained a consistent safety profile in all participants, with no significant differences between Parkinson’s patients with and without cognitive impairment.

“These compelling data reinforce our commitment to advancing buntanetap into a longer study, which will allow us not only to verify observed symptomatic improvements but also to explore buntanetap’s disease-modifying properties,” Maccecchini said.

Following a review of data from the Phase 2 trial, the U.S. Food and Drug Administration gave positive feedback to the company’s plans to launch a Phase 3 study to test buntanetap in late-stage Parkinson’s patients.