FDA Grants Orphan Drug Designation to Acute Lymphoblastic Leukemia Treatment, OBI-3424

This morning, September 19, 2018, the US Food and Drug Administration (FDA) granted an orphan drug designation to OBI Pharma, Inc.’s OBI-3424 for the treatment of acute lymphoblastic leukemia (ALL).

"This additional orphan drug designation for OBI-3424 by the FDA is a significant step in the development of this drug candidate in ALL, including T-ALL, an unmet medical need disease with limited treatment options,” said Amy Huang, general manager of OBI Pharma, in a recent statement. “We are excited that the FDA has recognized the need to develop novel targeted therapeutic agents such as OBI-3424 in the fight against ALL."

A first-in-class novel small-molecule prodrug, OBI-3424 targets cancers in which the enzyme aldo-keto reductase 1C3 (AKR1C3) is overexpressed; it selectively releases a DNA alkylating agent in the presence of the AKR1C3 enzyme.

OBI-3424 is being studied in a phase 1/2 clinical trial in patients with solid tumors, such as hepatocellular carcinoma (HCC) and castrate-resistant prostate cancer (CRPC), which has begun enrollment at the University of Texas M.D. Anderson Cancer Center.

Current primary outcome measures for the trial include a host of variables, such as the incidence and severity of adverse events (AEs), safety changes in electrocardiogram (ECG) and body weight, the number of participants with dose-limiting toxicities (DLTs), and defining the recommended phase 2 dose (RP2D).

Primary outcome measures regarding pharmacokinetics (PK) include the time to maximum concentration (Tmax), the maximum peak plasma concentration (Cmax), the magnitude of the slope of the linear regression of the log concentration vs. time profile during the terminal phase (Kel), the half-life (T1/2), and the under the concentration-time curve (AUClast).

The trial will be comprised of 2 experimental treatment arms. One arm will receive a dose escalation phase of OBI-3424 (1.0 mg/m^2 to 24.0 mg/m^2) via IV infusion on days 1 and 8 of each 21-day cycle to determine the MTD and RP2D. The other experimental arm will be a cohort expansion phase and receive OBI-3424 via IV infusion on days 1 and 8 of each 21-day cycle at doses established by the month-to-date (MTD) and RP2D.

Approximately 92 adult participants are expected to enroll in the trial with an anticipated primary completion date of August 31, 2021.

Previously, OBI-3424 was granted an orphan drug status for the treatment of HCC.