AbbVie Announces Positive Topline Results from Phase 3 VIALE-A Trial of VENCLEXTA (venetoclax) Combined with Azacitidine in Previously Untreated AML Patients Ineligible for Intensive Chemotherapy

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AbbVie Recently Announces Positive Top-Line Results from the Phase III VIALE-A (M15-656) Study of Venclexta (venetoclax) as First-Line Treatment for Acute Myeloid Leukemia (AML). The results demonstrated that the study met its co-primary endpoints: venetoclax plus azacitidine showed statistically significant improvements in overall survival (OS) and composite complete response rate (CR+CRi) compared to the placebo plus azacitidine group.

In this study, the safety profile was generally consistent with the safety observed in previous Phase I/II studies and the known safety profiles of each of the two drugs.

This is a randomized, double-blind, placebo-controlled study conducted in patients with newly diagnosed acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. In the study, patients were randomly assigned to receive either venetoclax plus azacitidine or placebo plus azacitidine.

As recommended by the Independent Data Monitoring Committee (IDMC) and in accordance with the pre-specified interim analysis plan, the study results will be reported early due to positive efficacy outcomes observed at the first overall survival (OS) interim analysis. The data will be submitted to the U.S. FDA and global regulatory authorities. The study results will be presented at upcoming medical conferences.

Currently, AbbVie is conducting two confirmatory Phase III studies (VIALE-A and VIALE-C). Last month, the company announced the latest results from the VIALE-C study, which evaluated newly diagnosed acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy, comparing the venetoclax plus cytarabine regimen with the placebo plus cytarabine regimen. The results showed that the study did not meet its primary endpoint of significantly improving overall survival (OS), but demonstrated a statistically significant improvement in the secondary endpoint of complete remission (CR) rate.

Analysts have pointed out that the mixed results from two pivotal Phase III trials will make it difficult for AbbVie to avoid competition in the AML market, where smaller but more targeted therapies are emerging. In November 2018, Astellas’ second-generation FLT3 inhibitor Xospata received FDA approval for the treatment of adult patients with relapsed or refractory AML harboring FLT3 mutations. In the same month, Pfizer’s SMO inhibitor Daurismo also gained FDA approval. Additionally, Novartis’ first-generation FLT3 inhibitor Rydapt was approved by the FDA in May 2017.

In 2019, the global sales of venetoclax reached $792 million, surpassing the combined total of the three aforementioned competing products. Among them, Xospata generated $80 million in sales over the most recent nine-month period; Daurismo and Rydapt, likely due to their lower sales figures, were not itemized separately in Pfizer’s and Novartis’s 2019 financial reports.

Acute myeloid leukemia (AML) is one of the most aggressive and difficult-to-treat blood cancers, with very low survival rates. Despite advances in existing treatments and care, the 5-year survival rate for patients diagnosed with AML remains at approximately 28%. It is estimated that around 160,000 people worldwide currently have AML, with an incidence rate of 103 new cases per 100,000 individuals.

Over the past three decades, there have been few treatment options for patients with acute myeloid leukemia (AML) who are ineligible for or unable to tolerate intensive chemotherapy or hematopoietic stem cell transplantation. The positive results from the VIALE-A study confirm that the venetoclax plus azacitidine regimen provides significant clinical benefit in newly diagnosed AML patients who are not eligible for intensive chemotherapy.

Venetoclax is a first-in-class drug that selectively binds to and inhibits the B-cell lymphoma-2 (BCL-2) protein. It was co-developed by AbbVie and Roche, with both companies jointly responsible for the U.S. market, while AbbVie handles markets outside the United States. To date, venetoclax has been approved in more than 50 countries/regions worldwide for: (1) the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL); and (2) the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML).

Reference Sources:

1、AbbVie Announces Positive Topline Results from Phase 3 Trial of VENCLEXTA (venetoclax) in Combination with Azacitidine in Patients with Acute Myeloid Leukemia (AML)

2、AbbVie, Roche's Venclexta nails confirmatory combo trial in AML after flopping earlier study