FDA Pauses Enrollment for Aprea’s Lymphoid Malignancy Trial

 

The U.S. Food and Drug Administration (FDA) has placed a clinical hold on Boston-based Aprea Therapeutics’ lymphoid malignancy clinical trial after the agency expressed concerns regarding the safety and efficacy data from a previous myelodysplastic syndromes (MDS) study. On the morning of the news, shares in APRE were down 12.20% at $3.60 during premarket.

Aprea’s clinical trial is evaluating a combination of eprenetapopt with acalabrutinib or with venetoclax and rituximab. Eprenetapopt, the company’s lead candidate, is a small molecule designed to reactivate the p53 mutant tumor suppressor protein. Up to half of tumors in humans express a p53 mutation that leads to treatment-resistant cancers and, ultimately, poor survival.

Eprenetapopt is undergoing investigation in combination with chemotherapy agent azacitidine in 20 patients in the company’s myeloid malignancy programs. These programs involve MDS, acute myeloid leukemia (AML) and post-transplant maintenance trials.

The most recent clinical hold issued by the FDA precludes enrollment of any additional patients until the hold is resolved; however, enrolled patients receiving a clinical benefit from their assigned therapeutic combination can continue to receive their treatment.

Last week, the FDA also placed a partial clinical hold on Aprea’s myeloid malignancy program. Similar to the most recent clinical hold, this one also doesn’t stop treatment in patients who are receiving benefit from their assigned regimen.

Christian S. Schade, chairman and chief executive officer of Aprea, said, “Safety is our highest priority,” in reference to the hold possibly being caused by observed toxicities in the trials. While Aprea didn’t divulge many details on the clinical trial holds, the company said it is working with the FDA, evaluating data and answering agency questions to resolve the hold and get enrollment back up and running.

“Based on the totality of the data we have for eprenetapopt, we believe that it continues to be a promising therapeutic option for cancer patients,” said Schade. “We are working closely with the FDA to review the data specific to eprenetapopt with azacitidine in our myeloid malignancy trials and will provide an update when we have additional information.”

In April, Aprea’s lead candidate eprenetapopt was granted Orphan Drug and Fast Track designations from the FDA in MDS and AML. In July, the company announced positive results from a Phase II trial of an eprenetapopt and azacitidine combination for post-transplant maintenance in TP53-mutant MDS and AML. At one year following transplant, approximately 58% out of 33 participants met criteria for relapse-free survival. Additionally, the overall survival was 79%.

While these data were generally positive, eprenetapopt didn’t meet a primary endpoint in a Phase III trial, findings of which were announced in December 2020. In this study, the complete response (CR) rate in patients with MDS was only 33.3% in the eprenetapopt plus azacitidine arm compared with 22.4% in the azacitidine monotherapy group. There was no statistically significant difference between these two arms in terms of the CR rate.