A week ago, Aprea Therapeutics was hit with an FDA partial clinical hold on its leading drug, eprenetapopt, in combo with other approved meds in a late-stage myeloid malignancy program.
Now, the U.S. regulator has gone further, hitting the biotech with a full hold for a lymphoid malignancy study that had initially been spared.
In a brief statement, the biotech said the FDA has placed a clinical hold on a test of eprenetapopt with AstraZeneca’s Calquence, or with Roche/AbbVie’s Venclexta and Roche/Biogen’s Rituxan, in lymphoid malignancies.
“No additional patients can be enrolled until the clinical hold is resolved, though patients on study deriving clinical benefit can continue to receive study treatment,” the company said.
Last week, the FDA put a partial clinical hold on tests of eprenetapopt with Bristol Myers Squibb’s Vidaza in the myeloid malignancy programs. At the time, the biotech said the partial clinical hold “does not apply to the company’s ongoing clinical trials in lymphoid malignancies and solid tumors, or the APR-548 clinical trial.”
But things have changed.
“Subsequent to receiving notification of a partial clinical hold on its myeloid malignancies program, Aprea was informed by FDA of a clinical hold on its lymphoid malignancy study,” the company added in Thursday morning’s update.
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“The FDA’s concerns referred to the safety and efficacy data from the phase 3 MDS clinical trial,” the statement said. The company gave no specific details on what the concerns are, but the hold is pretty damning given that safety and efficacy are the only things the FDA will look at.
Last week, the company said on a call with investors that the first partial hold was mostly related to low blood counts, which are “a hallmark” of patients with myelodysplastic syndrome. They tried to argue that given this precedent, it was hard to judge whether the drug was causing the issue, or the disease. Clearly, the FDA still has serious concerns.
Aprea will “work closely” with the FDA to sort these issues out and “seek to resolve the clinical hold as soon as possible.”
Eprenetapopt (aka APR-246) is a small molecule designed to reactivate mutant and inactivated p53 protein by restoring wild-type p53 conformation and function and kick-starting programmed cell death in cancer cells.
Even before this, the drug was in trouble: Back in December, Aprea said phase 3 data showed the med 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 BMS’ Onureg, but the results were not statistically significant. The drug also failed to hit secondary goals for overall response and duration of response.
The biotech’s shares were off 7% to $3.81 in premarket trading Thursday morning.