Cognitive measures may improve with buntanetap in Parkinson’s
Phase 3 trial points to improvements in thinking skills, biomarker reductions
- Phase 3 trial shows buntanetap may help preserve thinking in early Parkinson’s.
- The therapy was reported to reverse decline in amyloid-positive patients and reduce Alzheimer’s biomarkers.
- Buntanetap targets toxic brain proteins; an FDA meeting is planned for Parkinson's dementia treatment.
In people with early Parkinson’s disease, buntanetap slowed cognitive decline, with the biggest gains seen in those with mild dementia. Researchers also noted that about a quarter of these patients showed signs of amyloid buildup — a marker linked to Alzheimer’s disease — and had a faster cognitive decline. In this group, buntanetap was said to counteract and even reverse that decline.
That’s according to new data from a Phase 3 trial (NCT05357989), which tested the therapy in people with early Parkinson’s. Buntanetap also reduced the levels of biomarkers of neurodegeneration associated with Alzheimer’s disease, findings that are consistent with earlier trial data suggesting buntanetap halted cognitive decline in people with Parkinson’s.
Data will be presented in a scientific poster at the Clinical Trials on Alzheimer’s Disease (CTAD) conference, held in San Diego, Dec. 1-4.
“The findings integrate seamlessly with our growing body of clinical evidence, distinguishing buntanetap as a promising therapeutic candidate for cognitive improvement across multiple neurodegenerative diseases,” Cheng Fang, senior vice president of research and development of Annovis Bio, the treatment’s developer, said in a company press release.
Understanding Parkinson’s and how buntanetap may help
A key feature of Parkinson’s is the buildup of harmful clumps of misfolded proteins in the brain, especially a protein called alpha-synuclein, which is thought to damage and destroy nerve cells. This leads to motor symptoms like slowed movements, balance issues, and gait problems, along with nonmotor symptoms, such as mood changes and cognitive decline.
Buntanetap is an investigational oral therapy designed to reduce the production of toxic proteins in brain cells, including alpha-synuclein and proteins commonly linked to Alzheimer’s disease, such as beta-amyloid and tau.
Data from a previous Phase 1/2 trial (NCT04524351) showed buntanetap was well tolerated and was associated with improvements in cognitive and motor skills in Parkinson’s compared with a placebo. It also reduced overall disease severity and lowered blood levels of TDP-43, another protein that can form toxic clumps.
In the completed Phase 3 study, buntanetap improved motor function in people with early Parkinson’s who had been diagnosed more than three years earlier and in those with postural instability and gait difficulties. It slowed cognitive decline, particularly in participants with mild dementia, which involves challenges with memory, language, and thinking.
New data show that 25% of the trial participants had a buildup of amyloid protein — a hallmark of Alzheimer’s disease — and these patients experienced faster cognitive decline over the course of the study. According to the company, the decline “was counteracted and reversed by buntanetap.”
Reductions in several well-established biomarkers of neurodegeneration used in Alzheimer’s research — including pTau217, total tau, and brain-derived tau — were also observed in this group.
“What we see is that Parkinson’s patients who experience cognitive decline also have Alzheimer’s pathology, and our drug helps them,” Fang said. According to the company, these findings demonstrate that buntanetap is modulating the underlying causes of cognitive decline.
Annovis recently announced it will meet with the U.S. Food and Drug Administration to discuss buntanetap as a treatment for dementia due to Parkinson’s.
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