FDA Puts Eprenetapopt on Fast Track for Treating TP53 Mutant AML

FDA Puts Eprenetapopt on Fast Track for Treating TP53 Mutant AML

Eprenetapopt (APR-246), an investigational therapy being developed by Aprea Therapeutics, has been granted fast track designation by the U.S. Food and Drug Administration for treating acute myeloid leukemia (AML) with mutations in the TP53 gene.

Fast track designation, given to candidate therapies that show promise for serious diseases, is intended to accelerate the therapy’s development and expedite its approval by providing more frequent meetings with the FDA and discussions about the development plan.

“We are pleased to have received Fast Track designation for eprenetapopt in the treatment of TP53 mutant AML, a cancer for which outcomes are poor and there are no current therapeutic options specifically for these patients,” Eyal C. Attar, MD, chief medical officer of Aprea, said in a press release.

The TP53 gene provides instructions to make the tumor protein p53, a natural tumor suppressor that cells use to prevent uncontrolled growth. It arrests cell growth and promotes either DNA repair or cell death in cells with DNA damage or in stressful environments such as low oxygen or low nutrients.

Mutations in the TP53 gene — one of the most frequently mutated genes in human cancers — block p53 anti-tumor function, leaving cells more susceptible to uncontrolled growth. Mutations in this gene often are linked with resistance to therapy and poorer survival.

Eprenetapopt is a small molecule designed to promote the reactivation of the mutant and inactivated form of the p53 protein, and resulting in the death of cancer cells.

The candidate therapy has shown anti-tumor activity in preclinical research with solid and liquid tumors, including AML or myelodysplastic syndromes (MDS).

Eprenetapopt also showed potent synergy when given in combination with traditional anti-cancer therapies, e.g. chemotherapy, or immunotherapies.

According to Aprea, in a Phase 1/2 clinical trial, eprenetapopt was found safe and showed anti-tumor activity in blood and solid tumors that carried mutations in the TP53 gene.

Two ongoing clinical trials — a Phase 1/2 trial (NCT03588078) and a Phase 1b/2 (NCT03072043) — are testing the safety and effectiveness of eprenetapopt in combination with azacitidine (brand names Vidaza, Onureg) as a front-line therapy for AML patients with TP53 mutations, along with patients who have other blood cancers.

Two other eprenetapopt trials are currently recruiting. An open-label Phase 1 trial (NCT04214860) is assessing the safety and preliminary effectiveness of eprenetapopt when given in combination with Venclexta (venetoclax) — with or without azacitidine — in the treatment of front-line and relapsed or refractory adults with AML who are positive for TP53 mutations. More information is available here.

A Phase 2 trial (NCT03931291) is assessing the safety and effectiveness of APR-246 in combination with azacitidine as maintenance therapy after allogeneic hematopoietic stem cell transplant in adult patients with TP53 mutant AML or MDS. More information about that trial is available here.

Eprenetapopt has received breakthrough therapy, orphan drug and fast track designations from the FDA for MDS, as well as orphan drug designation from the European Medicines Agency (EMA) for MDS, AML and ovarian cancer.

“Emerging data from our AML trials evaluating eprenetapopt with azacitidine, and with eprenetapopt, azacitidine and venetoclax, are promising and we continue to enroll patients to identify the best treatment regimen. As these data mature in 2021, we look forward to continued interaction with FDA as we map out opportunities for an accelerated pathway to potential approval,” said Attar.