Very recently, eprenetapopt (APR-246), a small molecule that reactivates mutant and inactivated p53 protein, was granted orphan drug designation by the U.S. Food and Drug Administration (FDA) for the treatment of TP53-mutated acute myeloid leukemia (AML).1
TP53-mutated AML is associated with resistance to treatment and poor prognosis. Eprenetapopt restores wild-type p53 conformation and function, inducing apoptosis in cancer cells. In December 2020, eprenetapopt received FDA fast track designation for AML, as well as FDA breakthrough therapy designation, orphan drug designation, and fast track designation for the treatment of myelodysplastic syndromes (MDS). The agent also holds an orphan drug designation from the European Medicines Agency (EMA) for MDS, AML, and ovarian cancer.
The phase II Groupe Francophone des Myélodysplasies (GFM)-APR trial (NCT03931291) is currently investigating eprenetapopt combined with azacitidine for patients with AML or MDS harboring TP53 mutation. The study results, which can be found here, suggest encouraging safety and efficacy in this patient population.