Roche's Venclexta in Combination with Azacitidine Receives FDA Breakthrough Therapy Designation for Higher-Risk MDS

Compiled and translated by | Tom Li

Recently, Genentech, a member of the Roche Group, announced that the combination therapy of Venclexta (venetoclax) and azacitidine has been granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA).

According to the criteria of the Revised International Prognostic Scoring System (IPSS-R), this drug is intended for treatment-naïve adult patients with intermediate-, high-, and very high-risk myelodysplastic syndromes (MDS). The combination therapy was granted Breakthrough Therapy Designation (BTD), primarily supported by positive results from the Phase Ib M15-531 trial in patients with high-risk MDS. In addition to the Phase Ib M15-531 study, the drug is also being evaluated in the Phase Ib M15-522 study, which assesses the efficacy of the Venclexta and azacitidine combination therapy in patients with relapsed or refractory and newly diagnosed high-risk MDS.

Notably, this marks the sixth Breakthrough Therapy Designation (BTD) granted to Genentech’s Venclexta. Venclexta was developed by AbbVie and Roche, with its commercialization in the United States managed by Genentech, a member of the Roche Group. Receiving BTD status will accelerate the development and evaluation of new drugs to support the treatment of serious or life-threatening conditions. The designation is particularly beneficial for therapies that demonstrate clinically superior efficacy compared to currently available treatments.

Venclexta is an oral, selective B-cell lymphoma-2 (BCL-2) inhibitor that targets, binds to, and inhibits the B-cell lymphoma-2 protein. This protein accumulates in patients with certain types of hematologic malignancies. As BCL-2 accumulates in the body, cancer cells become more resistant to cell death and self-destruction. Venclexta blocks this protein and helps restore the natural process of apoptosis.

MDS, the indication for this combination therapy, is a rare hematologic malignancy that progressively impairs the bone marrow's ability to produce normal blood cells, ultimately leading to anemia, weakness, fatigue, and frequent infections. Without prompt and appropriate treatment, MDS can progress to acute myeloid leukemia (AML). This disease affects approximately 10,000 individuals annually in the United States, with a median overall survival of only 18 months for patients diagnosed with high-risk subtypes.

Venclexta has been approved in more than 80 countries worldwide. In the United States, Venclexta was previously approved by the FDA for previously untreated patients with chronic lymphocytic leukemia (CLL), patients with relapsed or refractory CLL, and previously untreated patients with acute myeloid leukemia (AML). Additionally, the drug is approved in combination with azacitidine, low-dose cytarabine, or decitabine for the treatment of newly diagnosed AML patients who are 75 years of age or older, or of any age with comorbidities. In the European Union, Venclexta is also approved for the treatment of newly diagnosed AML patients who are unfit for intensive chemotherapy.

In December 2020, Venclexta was successfully launched in China, becoming the first approved BCL-2 inhibitor in China. The drug received conditional approval from China's National Medical Products Administration (NMPA) for use in combination with azacitidine to treat newly diagnosed adult patients with acute myeloid leukemia (AML) who are either unsuitable for intensive induction chemotherapy due to comorbidities or are aged 75 years and older.

Reference: Genentech's Combo Therapy for Rare Blood Cancers Scores Breakthrough Designation