FDA Gives Green Light to Phase 3 Trial of Buntanetap
Annovis Bio has been given the go-ahead by the U.S. Food and Drug Administration (FDA) to begin a Phase 3 clinical trial to test buntanetap (ANVS401) as an oral therapy for early-stage Parkinson’s disease.
“With this FDA notice in hand, we are thrilled to start recruiting for the US clinical trial soon, expected later this summer,” Maria L. Maccecchini, PhD, Annovis Bio’s founder, president, and CEO, said in a press release.
Buntanetap, formerly known as ANVS401 or posiphen, is a small molecule that lowers the levels of particular proteins that can form insoluble, toxic clumps. These include alpha-synuclein in Parkinson’s and beta-amyloid and tau in Alzheimer’s disease. It works by halting the process — called translation — whereby cells use information in the DNA to produce proteins.
The approval follows the positive feedback and further recommendations by the FDA in a type B meeting early this year that included clinical goals, enrollment criteria, and other trial parameters.
The regulatory agency has agreed on the company’s final trial design, including its duration, from a previous one-month restriction to one that could last for decades, according to Annovi’s press release. It also has agreed on the use of a new batch of materials that meet the standards of good manufacturing practice (GMP) used to ensure consistency and quality during production.
The FDA’s decision on the long-term trial duration was based on preclinical safety data from mice, rats and dogs submitted by Annovis for review, along with chemistry and manufacturing data. The company also supplied data from more than 200 humans, including what was accumulated over the years in patients with Alzheimer’s, a condition for which buntanetap also is being tested.
“We are pleased that the FDA has approved our clinical trial design in early PD patients and called it a well-designed study. The positive FDA review affirms the Company’s path to securing approval for buntanetap to treat neurodegenerative diseases, including Parkinson’s and Alzheimer’s diseases, with longer treatment regimens,” Maccecchini said.
In a previous two-part Phase 2 clinical trial (NCT04524351), 14 people with Parkinson’s and 14 people with Alzheimer’s were randomly assigned to buntanetap (80 mg) or a placebo, given daily for 25 days.
The nine Parkinson’s patients who received buntanetap showed improvements in their speed and coordination, interim data showed.
An additional 40 patients with early-stage Parkinson’s were recruited for the trial’s second part where they received buntanetap — either at 5, 10, 20, or 40 mg — or a placebo, again for 25 days.
Data from all the Parkinson’s patients showed that buntanetap at doses of 5, 20, or 80 mg outperformed the placebo at improving cognitive skills over time, as measured by the scores on the Wechsler Adult Intelligence Scale (WAIS) coding test.
When given at daily doses of 10 or 20 mg, buntanetap also led to significant gains in the MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) overall score, a measure of disease severity.
The data suggested that buntanetap may lower alpha-synuclein levels, improving the health of nerve cells in the brain.
The Phase 3 trial will investigate the effectiveness, safety, and tolerability of buntanetap in those with early Parkinson’s. It will take place across different sites in Europe and the U.S. Participants, ages 40 to 85, will receive 10 or 20 mg of either buntanetap or placebo orally, once a day for six months.
The trial’s primary goal will look for changes in MDS-UPDRS part II and III scores, which reflect motor experiences of daily living and overall motor function. Secondary goals include looking for changes in total MDS-UPDRS scores, Participant Global Impression of Change (PGIC) and Clinical Global Impression of Severity of illness (CGIS).
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