Venclexta Faces Setback in Myelodysplastic Syndromes Trial

Roche and AbbVie's blood cancer drug Venclexta has encountered another obstacle in its development pipeline, this time failing to demonstrate a significant survival benefit in patients with myelodysplastic syndromes (MDS). The setback adds to a series of challenges for the BCL-2 inhibitor, which has shown promise in other hematological malignancies but struggles to expand its label.

Phase III VERONA Trial Results

The Phase III VERONA trial, which evaluated Venclexta (venetoclax) in combination with azacitidine against azacitidine alone in high-risk MDS patients, failed to meet its primary endpoint. According to a recent announcement, the combination therapy improved overall survival by less than 10%, falling short of statistical significance. The study included over 530 patients classified as intermediate, high, or very high risk based on international assessment standards.

Despite this setback, Roche and AbbVie emphasized that the results would not affect Venclexta's existing approvals. The companies plan to present full data from the VERONA trial at an upcoming scientific meeting and in a future publication.

Venclexta's Mixed Track Record

Venclexta, an oral small molecule that blocks the BCL-2 protein involved in cancer cell survival, has faced a series of challenges in recent years:

• In September 2023, the Phase III CANOVA trial in relapsed or refractory multiple myeloma failed to show a significant benefit in progression-free survival when Venclexta was combined with dexamethasone.

• A 2019 FDA clinical hold on multiple myeloma trials was triggered by a higher rate of deaths in a Phase III study. Although the hold was lifted after a few months, the BELLINI study that prompted the pause later showed a significant progression-free survival benefit but also detected an increased mortality risk.

Despite these setbacks, Venclexta remains a valuable asset for both Roche and AbbVie. The drug generated $2.6 billion in revenue in 2024, representing a nearly 16% year-on-year growth on an operational basis.

Implications for Future Development

The recent failure in myelodysplastic syndromes highlights the challenges of expanding Venclexta's indications beyond its current approvals, which include chronic lymphocytic leukemia and acute myeloid leukemia. As Roche and AbbVie continue to explore potential new applications for the drug, they will need to carefully balance its efficacy against safety concerns in various hematological malignancies.