RARE Daily

FDA Grants Aprea Breakthrough Therapy Designation for MDS Therapy

January 30, 2020

Rare Daily Staff

Photo: Christian Schade, CEO of Aprea

The U.S. Food and Drug Administration granted Aprea Therapeutics Breakthrough Therapy designation for its experimental therapy APR-246 in combination with azacitidine for the treatment of myelodysplastic syndromes with a susceptible TP53 mutation.

Myelodysplastic syndromes (MDS) represents a spectrum of hematopoietic stem cell malignancies in which bone marrow fails to produce sufficient numbers of healthy blood cells. Approximately 30 to 40 percent of MDS patients progress to acute myeloid leukemia (AML) and mutation of the p53 tumor suppressor protein is thought to directly contribute to disease progression and a poor overall prognosis.

The p53 tumor suppressor gene is the most frequently mutated gene in human cancer, occurring in about half of all human tumors. These mutations are often associated with resistance to anti-cancer drugs and poor overall survival, representing a major unmet medical need in the treatment of cancer.

APR-246 is a small molecule that has demonstrated reactivation of mutant and inactivated p53 protein – by restoring wild-type p53 conformation and function – and thereby induces programmed cell death in human cancer cells.  Pre-clinical anti-tumor activity has been observed with APR-246 in a wide variety of solid and hematological cancers, including MDS, AML, and ovarian cancer, among others. 

“Breakthrough Therapy Designation further supports our development program for APR-246 in combination with azacitidine in MDS patients with a TP53 mutation,” said Christian Schade, CEO of Aprea. “Outcomes for MDS patients with a TP53 mutation are poor and there are no current therapeutic options specifically for these patients.”

The FDA’s Breakthrough Therapy designation is intended to expedite the development and review of a drug candidate that is planned to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies on one or more clinically significant endpoints.

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