Published: June 18, 2025
Category: Clinical Trial | Hematology | Oncology
Written By: Team Pharmacally
In the latest development surrounding Venclexta (venetoclax), a flagship hematology drug from the Roche and AbbVie alliance, it has failed to attain its primary endpoint in a critical Phase III study for higher-risk myelodysplastic syndrome (MDS), announced by Roche-Abbvie Alliance on June 16 2025. This marks the second major trial setback for AbbVie and Roche with Venclexta. The drug had previously failed to meet its endpoints in the CANOVA study, which evaluated its use in relapsed or refractory multiple myeloma patients who tested positive for a specific biomarker and had undergone at least two prior lines of therapy
Trial Summary
The VERONA trial was a global, Phase III, randomized, double-blind study involving approximately 500 patients diagnosed with newly diagnosed higher-risk myelodysplastic syndrome (MDS). The trial compared venetoclax (400 mg on Days 1–14) in combination with azacitidine (75 mg/m²) versus azacitidine with placebo, administered in 28-day induction cycles. The study’s co-primary endpoints were complete remission (CR) rate and overall survival (OS). Despite earlier encouraging data from Phase 1b studies, the VERONA trial did not meet its primary endpoint. The trial failed to demonstrate a statistically significant improvement in overall survival when venetoclax was added to standard therapy. As of now, key outcome metrics such as the hazard ratio (HR), median OS values, and p-values have not yet been publicly disclosed. More detailed data are anticipated at upcoming scientific meetings or in peer-reviewed publications.
Despite initial promise and prior regulatory recognition, including an FDA Breakthrough Therapy Designation for various other ailments, the combination therapy did not result in a statistically significant improvement in overall survival in higher-risk MDS patients, which was the trial’s primary goal.
About Myelodysplastic Syndrome (MDS)
Myelodysplastic syndrome, also known as myelodysplasia or myelodysplastic neoplasm, is a group of conditions, mostly of cancerous etiology, that affect bone marrow and its ability to produce mature and healthy blood cells like RBCs, platelets, and WBCs. A result of a lack of mature cells in the blood leads to conditions like anemia, frequent bleeding, and infections; in some cases, patients may develop acute myeloid leukemia. Patients with higher-risk MDS face a poorer prognosis, with limited frontline therapeutic options beyond supportive care and hypomethylating agents like azacitidine.
Venclexta is a selective B-cell lymphoma 2 (BCL-2) inhibitor. In some blood cancers, BCL-2 prevents cancer cells from undergoing apoptosis, a natural death or self-destruction process. Venclexta inhibits the BCL-2 protein and works to help restore the process of apoptosis. It was being evaluated to determine whether it could drive deeper remissions and improved survival in this underserved patient population.
Venclexta’s Standing in Other Indications
It’s important to note that despite the VERONA trial setback for MDS, Venclexta (venetoclax) remains FDA-approved and widely used in the treatment of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML), specifically in adult patients who are unfit for intensive chemotherapy. The drug continues to hold an important place in modern hematology, having generated over $2.6 billion in global sales in 2024, which underscores both its clinical relevance and broad adoption in real-world practice.
Clinical Implications
While the outcome of the VERONA trial is disappointing, it provides meaningful insights for both clinicians and researchers. Even though the Venclexta is already approved for AML, The results underscore the distinct biological complexities between MDS and AML, despite their clinical similarities. As Venclexta was emerges as the hope for MDS patient after its positive phase I result, but failure of phase III study highlight the urgent and continuing need for effective frontline treatment options for patients with higher-risk MDS. On the safety front, no new adverse signals were reported, although a full safety profile will be presented at upcoming medical conferences.
In response to the trial results, Roche and AbbVie released a joint statement, saying, “Although this outcome is not what we hoped for, we remain committed to exploring novel therapeutic strategies in MDS and other hematologic malignancies.”
Conclusion and Pharmacally Perspective
The failure of Venclexta in the VERONA trial represents a disappointing moment in the pursuit of better treatments for higher-risk myelodysplastic syndromes. Yet, in science, not all setbacks are dead ends. This trial underscores the biological complexity of MDS and the ongoing need for innovation in hematologic oncology. For AbbVie and Roche, it offers lessons to refine future therapeutic approaches. For clinicians and patients, it reinforces the importance of rigorous, data-driven advancement.
At Pharmacally, we believe that every clinical trial, whether successful or not, contributes to the greater mission of advancing smarter, safer, and more targeted care. We will continue to monitor developments in this space and report on emerging therapies, translational research, and key regulatory updates that shape the future of blood cancer treatment
Reference
Study Of Venetoclax Tablet With Intravenous or Subcutaneous Azacitidine to Assess Change in Disease Activity In Adult Participants With Newly Diagnosed Higher-Risk Myelodysplastic Syndrome (Verona). http://clinicaltrials.gov/study/NCT04401748
Venclexta (venetoclax), Package Insert https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/208573s013lbl.pdf
AbbVie Provides Update on VERONA Trial for Newly Diagnosed Higher-Risk Myelodysplastic Syndromes, PRNewswire, https://www.prnewswire.com/news-releases/abbvie-provides-update-on-verona-trial-for-newly-diagnosed-higher-risk-myelodysplastic-syndromes-302481869.html?utm_source=chatgpt.com
Roche, AbbVie say trial of Venclexta in patients with myelodysplastic syndromes falls short, Fierce Pharma, https://www.fiercepharma.com/pharma/roche-abbvie-trial-venclexta-patients-myelodysplastic-syndromes-falls-short
Genentech Provides Update on Phase III Verona Study, Genentech, A member of the Roche Group, https://www.gene.com/media/press-releases/15068/2025-06-16/genentech-provides-update-on-phase-iii-v?utm_source=chatgpt.com