Annovis Bio wants its Alzheimer’s disease therapy to be better than Biogen’s Aduhelm, but the latest data shows the drug did not improve dementia symptoms, problem-solving, orientation or judgment, among other data points.
The company revealed a mixed—and confusing—bag of results from a small phase 2a study Wednesday night at the 2021 Alzheimer’s Association International Conference in Denver. Annovis said Posiphen, also known as ANVS401, improved cognition by 30% in 25 days, but the conference presentation appeared to show the drug did not beat placebo on many—if any—points.
Posiphen is being tested in both Alzheimer’s disease and Parkinson’s disease in the trial. Annovis told Fierce Biotech in an interview that data was available from 14 patients each in the study’s two arms.
In a slide presentation, Annovis said “there are positive trends” on orientation, judgment and problem solving, home and hobbies, but these results were not statistically significant. Posiphen also failed to improve the severity of dementia on a scale measuring the severity of cognitive impairment. Posiphen was unsuccessful in both Alzheimer’s and Parkinson’s.
On a measure of working memory and processing speed, Posiphen scored a 6.6 in Alzheimer’s patients and a 6.1 for Parkinson’s patients.
Shares of the company more than halved after the data was presented, falling from the prior close of $109 to $47 around 10 a.m. ET Thursday morning, despite the company’s claims of a positive breakthrough. Annovis’ shares have been an outlier among its Alzheimer’s-focused peers, rising exponentially since the Aduhelm news broke in early June.
According to ClinicalTrials.gov, the FDA’s clinical research database, the main goal of the study was to record the incidence of treatment-emergent adverse events. A secondary outcome was to measure the concentration of Posiphen in plasma.
Other outcomes included changes in functional impairment on various rating scales to assess the symptoms and severity of dementia and Parkinson’s disease.
The biotech told Fierce that the drug normalized biomarkers—a term that has become a buzzword in Alzheimer’s treatment since the FDA approved Aduhelm on the strength of biomarker data.
CEO Maria Maccecchini, Ph.D., touted normalization of levels of neurotoxic proteins and restoration of axonal health. She also said inflammation decreased and neurofilament light declined.
But none of these measures appears to be listed in the trial’s goals, according to ClinicalTrials.gov.
Nevertheless, Maccecchini went on to slam Aduhelm and claim that Posiphen works better. But the two drugs were not assessed on the same Alzheimer’s rating scale—meaning the results cannot be compared apples to apples.
“I don’t really feel in any way, shape or form that Aduhelm is even remotely as good as our drug. I mean, there’s just no comparison,” Maccecchini said.
She also suggested that Posiphen could be studied in combination with other drugs, noting that she was “just chatting” with AC Immune, which has Parkinson’s and Alzheimer’s therapies in the clinic as well.
“You know, we should combine our drugs. Every chronic condition is treated with a cocktail. Who says that using Aduhelm alone works? I mean, it works a little bit. OK, fine. But I don’t see any problem coming up with drug cocktails to make it better for different people,” Maccecchini said.
Berwyn, Pennsylvania-based Annovis expects more data around synaptic markers in the coming weeks and will meet with the FDA in late September or October to start discussing phase 3 studies, Maccecchini said. The 69-patient phase 2a study—which includes 54 Parkinson’s patients, according to the data presentation—is done, with the last patient coming off on Saturday, the CEO added.
The phase 3 studies will enroll hundreds of patients, including a three- to six-month short-term study and a two-year chronic study in Alzheimer’s patients, as well as one or two studies for Parkinson’s patients, she said.
“That will really prove everything. It will prove that we can give it short-term, and it will prove that we can give it forever,” Maccecchini said. She said the company has enough money to fund one phase 3 study, but she expected shares to “go up some.”
That’s not exactly what happened when the markets opened to reveal a bleak day for Annovis, which needs to raise another $200 million to $250 million to carry out additional studies, according to the CEO.
Editor’s Note: This story replaced an earlier version reviewing Annovis Bio’s Alzheimer’s disease data. This story was amended again at 11:40 a.m. ET on July 30, 2021 to clarify the results of the working memory and processing speed scores in Alzheimer’s and Parkinson’s.