RARE Daily

Aprea’s Experimental Therapy Misses Primary Endpoint in Late Stage MDS Trial

December 28, 2020

Rare Daily Staff

Aprea Therapeutics reported that the phase 3 trial of its experimental therapy eprenetapopt for the treatment of TP53 mutant myelodysplastic syndromes failed to meet its primary endpoint of complete remission rate.

Shares of the company fell 73 percent on the news.

Myelodysplastic syndromes (MDS) are a rare group of blood disorders characterized by abnormal development of blood cells within the bone marrow. Individuals with MDS have abnormally low blood counts and can experience dizziness, fatigue, weakness, shortness of breath, bruising and bleeding, frequent infections, and headaches. In some cases, MDS may progress to bone marrow failure or an acute leukemia. The exact cause of MDS is unknown though it sometimes runs in families. Treatment depends on the affected individual’s age, general health, and type of MDS and may include red cell and/or platelet transfusions and antibiotics.

Aprea’s phase 3 clinical trial was evaluating the safety and efficacy of its lead experimental candidate eprenetapopt with azacitidine (AZA) versus AZA alone in TP53 mutant MDS. The trial did not meet the predefined primary endpoint of complete remission (CR) rate.   Analysis of the primary endpoint at this data cut demonstrated a higher CR rate in the experimental arm receiving eprenetapopt with AZA versus the control arm receiving AZA alone, but did not reach statistical significance. In the intention-to-treat population of 154 patients, the CR rate in the eprenetapopt with AZA arm was 33.3 percent compared to 22.4 percent in the AZA alone arm.

While analysis of certain secondary endpoints appears to favor the experimental arm at this data cut, they are not significantly different. The median duration of overall survival was similar between the arms. Additional patients in the study who have not achieved a CR remain on study treatment and the data will be analyzed at future pre-specified time points as set forth in the statistical analysis plan. The combination of eprenetapopt with AZA appeared to be well-tolerated, with an adverse event profile that was similar to the company’s prior phase 2 clinical trials. Subsequent analyses of the trial data, including secondary endpoints, will be conducted as the duration of patient follow-up increases. Aprea expects to present the data at a future scientific conference.

“Though we are disappointed the topline results did not reach statistical significance, we continue to believe that eprenetapopt can offer clinical benefit to patients with TP53 mutant malignancies,” said Eyal Attar, chief medical officer of Aprea. “We will continue to analyze data as it matures and follow patients who are still receiving study treatment. Our other clinical trials continue to progress and we remain committed to pursuing our clinical development programs.”

Eprenetapopt is a small molecule that reactivates mutant tumor suppressor protein p53 and is in clinical development for hematologic malignancies and solid tumors. Eprenetapopt has received Breakthrough Therapy, Orphan Drug and Fast Track designations from the U.S. Food and Drug Administration for MDS, Fast Track designation from the FDA for acute myeloid leukemia (AML), and Orphan Drug designation from the European Commission for MDS, AML and ovarian cancer. Aprea is also developing a next generation small molecule reactivator of mutant p53 for oral administration.

Photo: Eyal Attar, chief medical officer of Aprea

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