Aprea Therapeutics Closes Out 2020 with Phase III Flop

Shares of Aprea Therapeutics plunged more than 77% in morning trading after the Boston-based company announced its late-stage cancer combination treatment failed to meet its primary endpoint of complete remission rate.

Aprea was investigating the combination of eprenetapopt and the chemotherapy drug azacitidine as a potential treatment for TP53 mutant myelodysplastic syndromes (MDS). The Phase III study assessed the combination against azacitidine alone in this indication. Aprea said the combination treatment appeared to demonstrate a higher complete remission rate than azacitidine alone, however, the results did not reach statistical significance.

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Eprenetapopt (APR-246) is a small molecule that has demonstrated reactivation of mutant and inactivated p53 protein. The drug, which is Aprea’s sole asset in the clinic, is designed to restore wild-type p53 conformation and function, which induces programmed cell death in the cancer cells. Eprenetapopt received Breakthrough Therapy, Orphan Drug and Fast Track designations from the U.S. Food and Drug Administration for MDS and Fast Track designation from the FDA for AML.

Eyal Attar, chief medical officer of Aprea, expressed his disappointment with the topline results from the Phase III study. Although the trial did not show a statistical significance for the combination therapy, Attar said the company believes eprenetapopt can still offer clinical benefit to patients with TP53 mutant malignancies.

“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,” Attar said in a statement.

In pre-clinical studies, anti-tumor activity was observed with eprenetapopt in a wide variety of solid and hematological cancers, including MDS, AML and ovarian cancer. Phase I/II data confirmed the efficacy observed in preclinical studies and also showed a favorable safety profile.

In its announcement, Aprea said in the intention-to-treat population of 154 patients, the CR rate in the eprenetapopt with azacitidine arm was 33.3%. The azacitidine alone arm had a CR rate of 22.4%. Patients in the Phase III study were randomized 1:1 for the combination treatment or azacitidine alone. Additional patients in the study who have not achieved a complete response 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 company said.

Aprea said analysis of secondary endpoints in the study, including overall response rate and duration of responses, also seems to show higher efficacy for the combination treatment. But, like the primary endpoint results, the data does not appear to be statistically significant. The median duration of overall survival at the primary data cut was similar between the arms, Aprea said.

Continued analyses of the trial data, including secondary endpoints, will be conducted as the duration of patient follow-up increases. Aprea said it expects to present the data at a future scientific conference.

Dec 28, 2020


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