Second FDA clinical hold for Aprea cancer drug cites safety data in another study

A previous failure of a clinical trial of Aprea Therapeutics’ lead drug continues to drive the company’s tests of the small molecule in other cancers. On Thursday, the company announced that the FDA had placed a clinical hold on trials of the drug in lymphomas, the second regulatory shutdown for the drug in a week.

The FDA’s clinical hold on the drug, eprenetapopt, cited no problem with the lymphoma study. According to Aprea of ​​Boston, the regulator has instead raised concerns about safety and efficacy data in a clinical trial that tested the drug for myelodysplastic syndrome (MDS), a type of cancer that affects the production of blood cells. That Phase 3 clinical trial tested the drug Aprea in combination with azacitidine, a chemotherapy drug used to treat MDS. Last December, the drug failed to meet its primary goal of showing complete remission.

Data from the failed study was provided to the FDA. During an Aug. 6 conference call, Aprea’s Chief Medical Officer, Eyal Attar, said the regulator pointed to a higher rate of serious adverse events in the treatment arm than in the control arm. In all serious adverse events in both arms, fatalities were due to infections.

“It should be noted that the serious side effects were largely due to low blood counts, which is of course a hallmark of patients with myelodysplastic syndrome, and in particular patients with myelodysplastic syndrome who receive azacitidine-based chemotherapy in treatment regimens,” Attar said. “As such, the side effects in both arms were in large part related to infections or bleeding and the consequences of low blood counts.”

Attar added that some of the complications reported in the study occurred weeks after the patients stopped taking the Aprea drug. In some cases, those problems arose after patients received other therapies to treat the underlying disease.

Aprea wants to treat cancer with drugs that activate p53, a protein that suppresses tumors. While p53’s cancer-fighting abilities are well documented, hitting that protein with a drug has eluded the efforts of many companies. Eprenetapopt is a small molecule designed to reactivate mutant but nonfunctional p53, restoring that protein’s ability to cause the death of cancer cells, but not normal cells.

The clinical trial in lymphomas is testing the Aprea drug in combinations, either with acalabrutinib or venetoclax and rituximab, drugs currently used to treat these cancers. The clinical hold means that no new patients can participate in the study. Patients in the study who are currently showing clinical benefit may continue to receive the experimental treatment. The complete clinical shutdown follows a partial clinical shutdown announced last week for tests of the Aprea drug in myeloid malignancies, which are cancers of the bone marrow and blood cells.

Aprea did not provide details on the FDA’s specific concerns. In announcing the full clinical hold, the company said it plans to work closely with the agency to answer its questions and resolve the matter.

Image by the National Cancer Institute

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