BioPharma, Pharma

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

For the second time in a week, the FDA placed a clinical hold on an Aprea Therapeutics cancer drug. The biotech said the agency cited safety and efficacy data from a prior failed clinical trial that tested the small molecule in a different form of cancer.



A previous clinical trial failure of Aprea Therapeutics’ lead drug continues to loom over the company’s tests of the small molecule in other forms of cancer. On Thursday, the company announced the FDA placed a clinical hold on studies of the drug in lymphomas, the second regulatory halt for the drug in the span of a week.

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The FDA’s clinical hold on the drug, eprenetapopt, did not cite an issue with the lymphoma study. Instead, according to Boston-based Aprea, the regulator raised concerns about the safety and efficacy data in a clinical trial testing the drug in myelodysplastic syndrome (MDS), a type of cancer affecting the production of blood cells. That Phase 3 clinical trial tested the Aprea drug in combination with azacitidine, a chemotherapy used to treat MDS. Last December, the drug failed to meet the main goal of showing complete remission.

Data from the failed study were provided to the FDA. Speaking on an Aug. 6 conference call, Aprea Chief Medical Officer Eyal Attar said the regulator pointed out a higher rate of serious adverse events on the treatment arm compared to the control arm. Across the serious adverse events in both arms, fatalities were due to infections.

“It should be noted that the serious adverse events were largely a consequence of low blood counts, which is of course a hallmark of patients with myelodysplastic syndrome, and particularly patients with myelodysplastic syndromes who are receiving azacitidine-based chemotherapy in treatment regimens,” Attar said. “As such, the adverse events across both arms were in large part related to either infections or bleeding and consequences of low blood counts.”

Attar added that some of the complications reported in the study occurred weeks after patients stopped receiving treatment with the Aprea drug. In some cases, those problems developed after patients had start other therapies to treat the underlying disease.

Aprea aims to treat cancer with drugs that activate p53, a protein that suppresses tumors. Though 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 non-functional p53, restoring that protein’s ability to trigger 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 that are currently used to treat these cancers. The clinical hold means that no new patients can enroll in the study. Patients in the trial who are currently showing clinical benefit may continue to receive the experimental treatment. The full clinical hold follows a partial clinical hold announced last week covering tests of the Aprea drug in myeloid malignancies, which are cancers of the bone marrow and blood cells.

Aprea gave no details about the FDA’s specific concerns. In its announcement of the full clinical hold, the company said it intends to work closely with the agency to address its questions and resolve the matter.

Image by the National Cancer Institute