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FDA grants APG-115 orphan drug designation for the treatment of AML and MDS

Oct 13, 2020
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On October 9, 2020, the U.S. Food and Drug Administration (FDA) granted APG-115 orphan drug designation for the treatment of acute myeloid leukemia (AML). APG-115 is an orally available, selective, small molecule inhibitor of MDM2 (an E3 ubiquitin-protein ligase), which works by blocking the MDM2-p53 interaction, thus activating the tumor suppressor activity of p53.1 In September 2020, this drug also received FDA orphan drug designation for the treatment of gastric cancer.2

APG-115 is the first MDM2-p53 inhibitor to enter clinical studies in China and is currently also being tested in the U.S. for the treatment of solid tumors. A phase Ib study (NCT04275518), investigating APG-115 as a single agent or in combination with cytarabine or azacitidine for patients with relapsed/refractory (R/R) AML or myelodysplastic syndromes (MDS), is currently recruiting in China.1,2

NCT04275518 study design2

  • An open label, phase Ib study to investigate the pharmacokinetics and pharmacodynamics of APG-115 in adult patients with R/R AML, or relapsed/progressed, high/very high-risk MDS.
  • Three-stage study:
    1. 3+3 dose escalation to determine dose-limiting toxicities and maximum tolerated dose of APG-115 as a single agent given orally, once daily from Days 1–7, every 28 days.
    2. 3+3 dose escalation to determine the dose-limiting toxicities and maximum tolerated dose of: APG-115 plus cytarabine 1mg/m2 intravenously, once daily, on Days 3–7 every 28 days in the AML cohort; or APG-115 plus azacytidine 75 mg/m2 subcutaneously, twice daily, on Days 1–7 every 28 days in the MDS cohort.
    3. Dose expansion of the combination regimens.
  • Secondary endpoints: Overall response rate and overall survival.
  • Estimated enrollment: 90 patients.

This second FDA orphan drug designation for APG-115 is hoped to accelerate global clinical development and commercialization and allow for more patients to benefit as soon as possible.

  1. Ascentage Pharma. Ascentage Pharma’s apoptosis-targeting drug candidates granted two more orphan drug designations by the US FDA. https://www.ascentagepharma.com/press-releases/ascentage-pharmas-apoptosis-targeting-drug-candidates-granted-two-more-orphan-drug-designations-by-the-us-fda/. Published Oct 9, 2020. Accessed Oct 12, 2020.
  2. Ascentage Pharma. Ascentage Pharma’s MDM2-p53 inhibitor APG-115 granted orphan drug designation by the FDA for the treatment of gastric cancer. https://www.ascentagepharma.com/press-releases/ascentage-pharmas-mdm2-p53-inhibitor-apg-115-granted-orphan-drug-designation-by-the-fda-for-the-treatment-of-gastric-cancer/. Published Sep 14, 2020. Accessed Oct 12, 2020.
  3. Clinicaltrials.gov. A phase Ib study of APG-115 single agent or in combination with azacitidine or cytarabine in patients with AML and MDS. https://www.clinicaltrials.gov/ct2/show/study/NCT04275518. Updated Aug 12, 2020. Accessed Oct 12, 2020.

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