Buntanetap found effective, safe in early Alzheimer’s trial: New data

Benefits of oral therapy seen for patients irrespective of APOE4 status

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

Share this article:

Share article via email
A half-full liquid prescription medicine bottle bears a label reading 'Clinical Trials.'

The safety and effectiveness of oral therapy candidate buntanetap are comparable in people with early Alzheimer’s disease regardless of whether they do or do not carry a genetic risk factor known as APOE4.

That’s according to new data from a Phase 2/3 clinical trial (NCT05686044) that tested three doses of buntanetap against a placebo in more than 300 patients with the neurodegenerative disease. The new results were announced last week by buntanetap’s developer Annovis Bio.

APOE4 is a genetic variant that has been identified as one of the strongest risk factors for Alzheimer’s. Everyone inherits two copies of the APOE gene, one from each parent. As such, individuals can either carry two copies of the APOE4 variant — thus known as being homozygous — just one copy of the variant, thus being heterozygous, or no copies.

In addition to being a major risk factor for developing Alzheimer’s, APOE4 status can affect the safety of treatments. Leqembi (lecanemab), which last year became the first Alzheimer’s therapy to win full approval from the U.S. Food and Drug Administration (FDA), carries a black box warning noting that it can cause amyloid-related imaging abnormalities (ARIA), a side effect marked by bleeding and/or swelling in the brain, which is not usually serious but can be fatal in rare cases. In patients on Leqembi, the risk of ARIA, including serious ARIA, is higher for people who are homozygous for APOE4.

Like Leqembi, buntanetap is designed to reduce toxic clumps of protein in the brain, though the two therapies have distinct mechanisms of action: Leqembi is an antibody therapy that targets toxic proteins directly, whereas buntanetap is designed to reduce clumping by modulating protein production. Buntanetap, formerly known as Posiphen or ANVS401, is also being investigated in Parkinson’s disease — which like Alzheimer’s is marked by toxic clumps of protein in the brain.

Recommended Reading
Bolts of lightning are pictured shooting out of a human brain.

Rare mutation found to stop spread of toxic tau clumps in Alzheimer’s

Developer Annovis is ‘encouraged’ by results in early Alzheimer’s

Among the participants in the Phase 2/3 buntanetap study, 33 were homozygous for APOE4, 126 were heterozygous, and the remaining 159 were non-carriers. Sub-analyses were conducted to compare safety and efficacy outcomes in these groups.

Findings from the overall study, which were announced last month, showed that patients given buntanetap experienced greater improvements in cognition than those given a placebo after 12 weeks, or about three months. Cognition was specifically measured with a test called the Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog11).

Results of the new analyses revealed that statistically significant improvements in ADAS-Cog11 scores were seen irrespective of APOE4 status. Among early Alzheimer’s patients given buntanetap, ADAS-Cog11 scores improved by 3.3 points on average. In APOE4-positive patients, the average improvement was 3.15 points with buntanetap at a dose of 15 mg/day.

Safety data also were similar between both carriers and non-carriers; no cases of ARIA were reported.

Annovis stated it is “encouraged by these results.” As previously announced, the company is now planning to launch an 18-month Phase 3 trial in early Alzheimer’s patients. Annovis said the upcoming study “aims to further validate Buntanetap’s efficacy and safety profile and will be conducted under the guidance of the FDA.”