Aprea's myeloid program iced by FDA while tricky adverse event profile is sorted out

The FDA slapped a hold on Aprea Therapeutics’ myeloid malignancy programs for eprenetapopt after serious side effects cropped up in trial patients. But the high-risk nature of the patients’ disease and prior treatment means the biotech is not quite sure whether their drug caused the events.

After examining raw data from an open-label phase 3 trial in patients with myelodysplastic syndrome, the FDA decided to pause the entire program while the safety risks are sorted out. The FDA was specifically concerned that there appeared to be more serious side effects in the eprenetapopt arm of the trial. Patients who are benefiting from treatment will be allowed to continue.

Eprenetapopt is in trials to treat myelodysplastic syndrome and acute myeloid leukemia as well as for post-transplant maintenance in combination with Bristol Myers Squibb’s leukemia drug Onureg. All three of these studies are now on hold, but separate trials in lymphoid malignancies and solid tumors will carry on, Aprea said.

In December, Aprea reported that the phase 3 trial at issue failed to meet its goal of achieving a complete remission rate. The trial did find a higher rate of complete remission when eprenetapopt was paired with Onureg, but the results were not statistically significant. The drug also failed to hit secondary goals for overall response and duration of response.

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The company did not report safety data with the December top-line results, beyond saying that eprenetapopt had shown a “favorable safety profile” in a previous phase 1/2 clinical trial and preclinical testing.

Chief Medical Officer Eyal Attar, M.D., said during a Friday morning conference call that the serious side effects that caught FDA's eye were mostly related to low blood counts, which are “a hallmark” of patients with myelodysplastic syndrome. Some patients died from infections, but Attar said those deaths happened in both the treatment arm and the control group.  Aprea will provide additional context when it submits its response to the FDA, he said.

“It should also be pointed out that some of the adverse events occurred weeks after stopping study treatment. Some of the adverse events occurred after disease progression or even after the patients had started other therapy for their underlying disease,” Attar said.

The CMO also said the open-label study had a higher level of dose modifications and dropouts among higher-risk patients in the treatment arm. This could have affected the trial’s failure and the adverse event profile.

“In this population of high-risk patients already prone to infections, or bleeding or also receiving myelosuppressive chemotherapy, it can be very, very challenging to sort out whether there is any potential contribution to adverse events when novel agents are added to standard chemotherapy,” Attar said. “As such we are eager to work with the agency to resolve this question.”

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An independent data safety monitoring board previously reviewed the same top-line data examined by the FDA and found no safety events that would warrant stopping or changing the protocol, Aprea CEO Chris Schade said during the call.

Aprea could not say when it may have a response ready for the FDA to attempt to get the hold lifted nor when the next update on the programs might be available.

“We would love to provide a precise timeline for when this would all roll out,” Schade said. "Right now we’re just diagnosing the information that we got. This is all happening in real time.”

The company's shares were trading steadily after market open Friday, down just 5% to $4.08.