FDA Approves Venclexta-Rituxan Combo Therapy for CLL/SLL Patients

FDA Approves Venclexta-Rituxan Combo Therapy for CLL/SLL Patients

The U.S. Food and Drug Administration (FDA) has approved a combination treatment of Venclexta (venetoclax tablets) with Rituxan (rituximab) for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to AbbVie, one of the developers of Venclexta.

Venclexta plus Rituxan — co-marketed by Genentech and Biogen — is the first oral, chemotherapy-free combination in CLL that gives patients an option for a fixed duration of treatment, allowing them to stop treatment after nearly two years, AbbVie said.

The new combo strategy is intended for patients with or without a genetic deletion in chromosome 17 (the 17p deletion) who have received at least one prior therapy. A deletion in chromosome 17 is highly correlated with unfavorable outcomes with standard CLL treatments, and is found in up to 50% of CLL patients who relapse or do not respond to treatment.

The approval was based on results from the MURANO Phase 3 trial (NCT02005471), which compared the effectiveness and safety of the Venclexta plus Rituxan with that of standard chemotherapy regimen — Treanda (bendamustine) plus Rituxan.

The multicenter, open-label study included 389 CLL patients (median age 65) who had failed to respond, or progressed, after at least one prior treatment.

Results revealed a significant improvement in the length of time during or after treatment without disease worsening, with Venclexta plus Rituxan decreasing the risk of disease progression or death by 81% when compared to Treanda plus Rituxan.

Patients taking the combination also showed an overall response rate (ORR) — the portion of patients with a pre-defined cancer size reduction over a minimum time period —  of 92%, compared to 72% in the other group.

Safety results of the newly approved combination were in line with the known safety profile of Venclexta, which is developed by AbbVie and Genentech. The most frequent negative reactions – occurring in at least 20% of treated patients – were diarrhea, upper respiratory tract infection, cough, fatigue, nausea, and low levels of neutrophils, a type of white blood cell.

In the Venclexta group, 16% of patients stopped treatment due to adverse events, while 15% reduced dosing. Serious adverse events were reported across 46% of trial participants, with pneumonia being the most common (9%).

“Venclexta now gives indicated patients a new opportunity to significantly reduce the risk of their disease progressing, compared to a current standard of care,” Michael Severino, MD, said in a press release. Severino is executive vice president, research and development, and chief science officer at AbbVie. “This is an important step for patients and we look forward to continuing to provide new treatment options for people living with difficult-to-treat blood cancers.”

John Seymour, PhD, MURANO’s lead investigator, said: “The approval of the combination of Venclexta plus rituximab (Rituxan) for patients with relapsed or refractory CLL or SLL validates the results seen in the Phase 3 trial, including the significant improvement in progression-free survival.” Seymour also mentioned that progression-free survival “is considered a gold standard for demonstrating clinical benefit in oncology.”

Venclexta selectively suppresses Bcl-2, a protein highly elevated in CLL cells, which helps them escape cell death.

The FDA also decided to expand the use of Venclexta as stand-alone therapy for CLL or SLL patients, with or without 17p deletion, who have received one previous treatment. CLL and SLL are closely related. However, unlike CLL, SLL cancer cells are typically found in lymph nodes and the spleen rather than bone marrow and blood.

The FDA previously granted Venclexta four breakthrough therapy designations. A breakthrough therapy is a drug that either alone or in combination with other drugs is shown to demonstrate substantial improvement over existing therapies in a serious or life-threatening illness. In April 2016, the agency approved Venclexta as a stand-alone treatment for CLL patients with 17p deletion, who had received at least one prior therapy.

Rituximab was first approved by the FDA in 1997 for certain advanced nonHodgkin’s lymphomas.

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