Just over two weeks after boldly deciding to forge on with an Alzheimer’s disease drug despite a failed phase 2/3 clinical trial, Cortexyme now says it will use a lower dose in studies to come.
South San Francisco, California-based Cortexyme announced the dosing selection in a presentation of data (PDF) from the split phase trial at the 14th Clinical Trials on Alzheimer’s Disease (CTAD) conference Thursday. The results are mostly what we’ve already heard from the company: Atuzaginstat failed to meet the main goal of the GAIN trial by demonstrating a slowing of cognitive decline.
Cortexyme is taking a different approach than its peers by trying to show a connection between a reduction of Porphyromonas gingivalis infection and cognitive decline. Despite the failure, the biotech still heralded the trial as a win and claimed the data showed a relationship between the infection and Alzheimer’s. The company also pointed to a subpopulation of patients with mild to moderate disease who have a P. gingivalis infection as evidence of atuzaginstat’s efficacy.
That message was trumpeted again in the Thursday release and in a presentation at the CTAD conference, which zeroed in on the subpopulation data. But what is new is that Cortexyme has decided on the lower dose for future trials based on information from the study.
The therapy was associated with “dose-related liver enzyme elevations” three times the normal level, which rose depending on the amount of medicine administered. The company said the elevations “were not clinically significant and virtually all participants were asymptomatic.” But two patients in the highest 80-mg dose group had concomitant bilirubin elevation, which is a hallmark of liver dysfunction.
Liver damage previously plagued the GAIN trial in February, when “hepatic adverse events” forced the study into a partial clinical hold.
Atuzaginstat was not associated with any amyloid-related imaging abnormalities, or ARIA, an adverse event meaning swelling in the brain that has clouded Biogen’s Aduhelm. A 75-year-old female patient being treated with Aduhelm reportedly died in Canada after ARIA was detected.
Cortexyme claimed a 30% to 50% slowing of decline with the 40-mg dose, which is what will move forward in the next study.
“Our ability to identify the right population in historically hard to treat mild to moderate Alzheimer’s patients, along with finding an efficacious dose with a differentiated safety profile, is important progress toward a breakthrough treatment for Alzheimer’s disease,” Cortexyme Chief Medical Officer Michael Detke, M.D, Ph.D., said in a statement.
One of the study’s investigators compared the identification of the P. gingivalis patient population to personalized medicine common in oncology or HIV.
Cortexyme CEO and Chairman Casey Lynch said the phase 2/3 data will be used as the company embarks on a confirmatory study, “pending discussions with the FDA and global regulators.”
The company’s shares lost 76% of their value after the phase 2/3 results were issued in late October, settling at around $13 apiece. The shares have risen back up to the $14 range since then and were hovering in the red ever so slightly—down 1%—as the markets opened Friday.