Orphan Drug Designation Granted to ASLAN003 for Acute Myeloid Leukemia Treatment

The US Food and Drug Administration (FDA) has granted an orphan drug designation to ASLAN Pharmaceuticals’ ASLAN003 for the treatment of acute myeloid leukemia (AML).

ASLAN003 is an orally active, potent inhibitor of human dihydroorotate dehydrogenase (DHODH) that has the potential to be first-in-class in AML, according to the clinical-stage biopharmaceutical company. Since inhibition of DHODH depletes the intracellular pool of pyrimidines and contributes to lower levels of adenosine triphosphate, this action leads to the induction of the tumor suppressor p53, which at high levels can trigger apoptosis, or programmed cell death.

Currently, ASLAN003 is being assessed in a phase 2 clinical trial in Asia. The current primary outcome for the trial is the overall complete remission (OCR) rate as measured in the timeframe of 4 months after Leadership Practices Inventory (LPI). The OCR is defined as the proportion of patients with a best response of complete remission (CR) or complete remission with incomplete hematologic recovery (CRi), defined in accordance with the IWG Response Criteria in AML from day 29. Treatment failure is defined as not achieving any response 4 months after study treatment.

Secondary outcome measures include incidence of Adverse Events (AEs) as categorized in accordance with CTCAE 4.03 and changes from baseline in safety parameters (including vital signs, ECG parameters, clinical laboratory tests) as measured through 28 days post-last study medication administration; Relapse Free Survival defined as the time the criteria for remission (CR or CRi) are first met until there is evidence of patient relapse, regardless of whether the patient is still taking study drug as measured through study completion, an average of 6 months; Clinical Benefit Rate defined as the proportion of patients with an AML IWG best response of CR, CRi or PR as measured in the timeframe of 4 months after LPI; and the tumor % change defined from baseline in BM blasts at day 29 as measured in the timeframe if 29 days after LPI.

A total of up to 8 patients will be enrolled in this study, with 6 patients in each dose cohort: 1 cohort will receive 100 mg of ASLAN003 once daily (QD), another will receive 200 mg QD, and the last cohort will receive 300 mg QD. Additionally, part 2 of the trial will look at an expansion cohort consisting of 20 patients who will be recruited to identify the optimum dose of the drug, which will be selected by the steering committee. The optimum dose will be selected from at least 1 cohort showing a tolerable safety profile and clinical benefit in disease presentation.

Interim data from the phase 2 trial is expected to be reported in the second half of 2018.

In previous clinical trials, ASLAN003 exhibited potent inhibition of DHODH—up to 2 orders of magnitude stronger than first generation DHODH inhibitors. The investigational drug also exhibited a lack of toxicities correlative with first generation inhibitors and other novel therapies for AML, and showed potential to induce differentiation in blast cells; it also demonstrated applicability in a broad range of AML patients.