Annovis Bio heralded a “significantly higher rate of improvement” in patients with Alzheimer’s disease who received buntanetap. However, digging a little deeper into the muddled readout suggests the trial was a failure.
The Pennsylvania biotech said that buntanetap was successful in the mid-stage portion of a phase 2/3 trial. The therapy led to a “significantly higher rate of improvement” on a scale of cognitive dysfunction called the Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11) when compared to placebo in patients who had mild Alzheimer’s disease, according to the company’s Monday morning release. The scale measures the efficacy of antidementia treatments by assessing language and memory.
Annovis also claimed that treatment led to improvement in cognition on the Alzheimer’s Disease Cooperative Study Clinician’s Global Impression of Change scale (ADCS-CGIC), which assesses clinically meaningful changes in clinical trials of the disease.
But if you read past the press release’s positive spin, the company eventually admitted what really matters—the main goal of the study was not met. The trial was actually assessing a statistically significant outcome in ADCS-CGIC or ADCS-ADL. ADCS-ADL is yet another Alzheimer’s scale that measures activities of daily living in patients with the neurodegenerative disorder.
“During the trial, ADCS-CGIC in all groups of patients barely changed, with no statistically significant difference observed. The 15 mg and 30 mg buntanetap groups slightly improved in mild AD patients. The subjective nature of this assessment allowed for a greater placebo effect, particularly in the advanced Alzheimer’s population, as patients and caregivers were likely hopeful for change,” the April 29 release said.
Trading of Annovis was briefly halted Monday morning. The company closed Friday at $18 and dropped 60% to $6.55 after trading resumed as of 11:44 a.m. ET today.
Elsewhere in the release, Annovis said there was an improvement in cognition. But in a note attached to that claim the company said that the initial recruitment for the trial did not include prescreening for Alzheimer’s biomarkers in the plasma.
“When we became aware of issues from other AD studies with sites recruiting non-AD patients, we fast-tracked biomarker measurements by collaborating with C2N Diagnostics. This enabled us, when we unblinded the data, to tell which patients had confirmed AD and which did not,” Annovis said.
Out of 325 patients who had completed the phase 2/3 trial, 202 had biomarkers indicative of the disease. Annovis then split this group into 112 patients with moderate disease and 90 who had mild disease. “These two selections were not pre-specified analyses,” the company said.
The company claimed an improvement in the mild patient group.
Nevertheless, Annovis will move the trial on.
“This short study shows a symptomatic effect with a possible disease-modification trend according to the tau data. The next study will have a longer duration, improved design and be statistically powered to validate symptomatic improvement and disease modification,” the release explained.
The company plans to request a meeting with the FDA in the next two to three months and move on to a phase 3 study that will test the drug over 18 months instead of 12 weeks. This new late-stage test will focus on biomarker-positive patients with early Alzheimer’s.
“It’s really exciting to see that this study confirmed what we have observed in the previous phase 2 studies in both the improvement of patients’ cognition and the improvement of biomarkers. We are unaware of any double-blind, placebo-controlled studies demonstrating this level of improvement in the ADAS-Cog 11 after one and after three months,” the company said in a statement attributed to Melissa Gaines, senior vice president of clinical operations, and Cheng Fang, Ph.D., senior vice president of research & development.
Buntanetap is also being tested for Parkinson’s disease. A key readout was due earlier this year but never arrived as planned. The company has yet to provide a timeline for the release of the data.
Previously known as Posiphen or ANVS401, buntanetap sent Annovis’ shares tumbling in July 2021 on negative data for Alzheimer’s disease. While the company claimed it was better than Biogen and Eisai’s Aduhelm—a drug that has since been pulled from the market—the data actually showed it had failed to beat placebo.