- The Food and Drug Administration has ordered California biotech Cortexyme to stop testing of an experimental Alzheimer's disease drug, notifying the drugmaker in a Jan. 25 letter that it placed a hold on clinical study of the treatment.
- As a result, Cortexyme said Wednesday it plans to "immediately" begin cutting costs while shifting its focus to an earlier-stage drug. In an email to BioPharma Dive, a company spokesperson said Cortexyme will provide a full update on its development plans "in the next week or so."
- The hold applies to Cortexyme's drug atuzaginstat, which recently failed to show a benefit in a large trial of people with mild or moderate Alzheimer's. The biotech, however, had claimed positive signs in a subgroup of study participants and planned to run another trial before the FDA's decision to place the program on hold.
Cortexyme is pursuing an unorthodox approach to treating Alzhiemer's, following intriguing evidence that suggests infection by the bacteria P. gingivalis could be a cause of the disease in some cases.
But the negative results from Cortexyme's Phase 3 study of atuzaginstat, disclosed last October, dealt a blow to that hypothesis and raised serious questions about the drug's future. In November, Cortexyme said it would conduct another trial to test whether the positive signs it saw in some participants were a real indication of potential benefit to treatment.
Now, the biotech appears to resetting and shifting resources to a second-generation drug that is designed to work similarly to atuzaginstat.
According to the company spokesperson, the hold on atuzaginstat is related to liver side effects observed in clinical testing — the same reason the FDA placed a "partial" clinical hold on the drug last February, which restricted enrollment and treatment for an open-label extension study.
In atuzaginstat's Phase 3 trial, 15% of participants who were given a higher, 80 milligram dose of the drug experienced spikes in liver enzymes that can be a warning sign for liver toxicity. Two of those participants also had elevations in a liver compound called bilirubin. Raised levels of liver enzymes and bilirubin together can indicate a risk for drug-induced liver injury.
At the time, the company said "virtually all" participants with liver enzyme elevations had been asymptomatic and planned to focus the next trial of atuzaginstat on a lower, 40 milligram dose. Still, some participants had discontinued the trial due to abnormal laboratory values.
When announcing the Phase 3 results, Cortexyme executives were optimistic another study would prove atuzaginstat's benefit in Alzheimer's. With the hold, though, Cortexyme is now looking at other diseases for the drug.
"We believe there are additional opportunities for clinical development of atuzaginstat in several therapeutic areas," the spokesperson wrote.
Shares in Cortexyme fell by nearly a third in Wednesday morning trading on news of the clinical hold.