Biopharma’s acute myeloid leukaemia treatment gains orphan drug designation

Clinical-stage biopharmaceutical company, ASLAN Pharmaceuticals, has been granted orphan drug designation (ODD) for its treatment for acute myeloid leukaemia (AML) — ASLAN003 — by the US Food and Drug Administration (FDA).

The orally active, potent inhibitor of human dihydroorotate dehydrogenase (DHODH) has the potential to be a first-in-class for AML — a cancer of the myeloid line of blood cells. DHODH is an enzyme that controls the rate limiting step in the de novo synthesis of pyrimidines, essential building blocks for the production of DNA and RNA in mammalian cells. Additionally, it contributes to the production of adenosine triphosphate, or ATP.

In cancer, increased levels of pyrimidines and ATP are required for tumour growth and survival. Inhibition of DHODH depletes the intracellular pool of pyrimidines and contributes to lower levels of ATP. This leads to the induction of the tumour suppressor p53, which at high levels of induction triggers apoptosis, or programmed cell death.

Currently, ASLAN is conducting a Phase II clinical trial in Asia to develop ASLAN003 in AML and is anticipating interim data from the trial to be available in the second half of the year (2018). In previous clinical studies, the therapy has demonstrated potent inhibition of DHODH (up to two orders of magnitude stronger than first generation DHODH inhibitors), lack of toxicities associated with first generation inhibitors and other novel AML therapies, and the potential to induce differentiation in blast cells and applicability in a broad range of AML patients.

ODD is granted by the FDA to drugs that are intended for the treatment of rare diseases or conditions that affect fewer than 200,000 patients in the US. The majority of the total AML patient population comprise those patients who have failed on standard of care chemotherapy or are unresponsive to chemotherapy.