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FDA has granted breakthrough therapy designation to venetoclax in combination with azacitidine for MDS

Jul 29, 2021

On July 21, 2021, the U.S. Food and Drug Administration (FDA) granted breakthrough therapy designation to venetoclax (in combination with azacitidine) for the treatment of adult patients with previously untreated intermediate- to very high-risk myelodysplastic syndromes (MDS).1 This approval was based on the results of the phase Ib M15-531 study.

Venetoclax has previously been approved for combination treatment of newly diagnosed acute myeloid leukemia (AML), previously untreated chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL), and for previously treated CLL


MDS are a group of hematologic malignancies that alter the ability of the bone marrow to produce normal blood cells. Patients with MDS often feel weak, suffer from frequent infections, anemia, and fatigue which can reduce their quality of life. MDS can progress to AML, and the median survival of higher-risk MDS is approximately 18 months.1


  • An oral, first-in-class inhibitor of the B-cell lymphoma-2 (BCL-2) protein, venetoclax blocks BCL-2, enabling cancer cell death (apoptosis).1

M15-531 trial results pertinent to this approval

  • A multicenter phase Ib, open-label, nonrandomized, dose-finding trial, designed to evaluate venetoclax in combination with azacitidine for the treatment of untreated patients with higher-risk MDS.1
  • Patients included in the study were classed as higher-risk MDS if they belonged to one of the following categories:
      • International Prognostic Scoring System (IPSS) categories intermediate-2 or high (overall IPSS Score ≥1.5)
      • Revised IPSS (IPSS-R) categories intermediate, high, or very high (Score >3)
  • The study aimed to determine the recommended phase II dosing schedule of the combination venetoclax with azacitidine.

FDA decision

As mentioned above, the FDA granted venetoclax in combination with azacitidine breakthrough therapy designation following the interim results from the M15-531 study.1 This designation aims to accelerate the development of medicines for the treatment of serious conditions based on preliminary evidence demonstrating an improvement over existing treatment options. Higher-risk MDS is associated with reduced quality of life, a poor prognosis, and has limited therapeutic options. This designation has the potential to improve outcomes for patients with MDS.

  1. Business Wire. FDA grants breakthrough therapy designation for venclexta in combination with azacitidine for the treatment of patients with myelodysplastic syndromes. Published Jul 21, 2021. Accessed Jul 26, 2021.