Venclexta Treatment Combo is Being Reviewed by FDA For CLL

Treatment with the fixed-duration, all-oral combination regimen of Venclexta (venetoclax) and Calquence (acalabrutinib) was submitted to the U.S. Food and Drug Administration (FDA) for a supplemental new drug application by AbbVie, according to a news release from the company, for patients with previously untreated chronic lymphocytic leukemia (CLL).

A supplemental new drug application is a request that is submitted to the FDA that is propositioning a request to change an already approved new drug application, and can aim to address changes such as labeling, dosage, manufacturing process, or new indications for use.

In this instance, the submission was prompted by notable results from the phase 3 AMPLIFY trial. The combination regimen of Venclexta and Calquence improved progression-free survival outcomes compared with standard chemoimmunotherapy for patients with previously untreated CLL.

“This FDA submission marks a milestone for CLL treatment with the potential approval for the first oral combination regimen of Venclexta and acalabrutinib for previously untreated patients with chronic blood cancer. This new fixed-treatment duration approach could allow patients the opportunity for time off treatment, if approved, and be potentially practice-changing in frontline CLL care,” said Svetlana Kobina, vice president of Global Medical Affairs, Oncology at AbbVie.

Moreover, the news release went on to state that, “[The] regimen offers an opportunity for patients to take time off treatment, an important step toward improved disease management.”

Trial Design

The global, multi-center, phase 3 AMPLIFY clinical study is evaluating treatment with Venclexta plus Calquence either alone or in combination with obinutuzumab (Gazyva) compared with chemoimmunotherapy for those with previously untreated CLL without del(17p) or TP53 mutation.

The data which supported the new application were presented at the 2024 American Society of Hematology Annual Meeting Data demonstrated that the fixed-duration combination of Venclexta and Calquence reduced the risk of disease progression or death by 35% compared with chemoimmunotherapy. Notably, regarding safety, the toxicity profile of the Venclexta combination aligns with the established profiles of each agent when administered individually. The most commonly reported side effects of any grade among patients receiving the combination were neutropenia and hemorrhage.

Neutropenia was the most frequent grade 3 or higher side effects, occurring in 26.8% of patients. Among events of clinical interest, tumor lysis syndrome was infrequent; events of any grade occurred in 0.3% of patients receiving the combination versus 3.1% of those receiving chemoimmunotherapy.

No new safety signals were identified in the AMPLIFY study.

What is Venclexta?

Venclexta is a first-in-class therapy that selectively targets and inhibits the B-cell lymphoma-2 (BCL-2) protein. In certain hematologic malignancies, BCL-2 functions to block apoptosis, the natural process of programmed cell death. By inhibiting BCL-2, Venclexta is designed to help reinitiate apoptosis in cancer cells.

Venclexta is being co-developed by AbbVie and Roche. In the United States, it is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, and by AbbVie outside the United States. Importantly, Venclexta has received regulatory approval in more than 80 countries, including the United States.

Currently, Venclexta is approved for the treatment of adults with CLL or small lymphocytic lymphoma (SLL), either as monotherapy or in combination with other agents. It is also approved in combination with Vidaza (azacytidine), decitabine, or low-dose cytarabine for adults with newly diagnosed acute myeloid leukemia (AML) who are age 75 or older or who have comorbidities that preclude the use of intensive chemotherapy.

These indications reflect its role in managing hematologic malignancies by restoring the process of apoptosis through selective inhibition of the BCL-2 protein in cancer cells, the news release concludes.

Reference

1. “AbbVie Submits for U.S. FDA Approval of Combination Treatment of VENCLEXTA® (venetoclax) and Acalabrutinib for Previously Untreated Patients with Chronic Lymphocytic Leukemia (CLL),” by AbbVie. News release. July 29, 2025.

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