FDA gives nod to AbbVie-Roche cancer combo

Venclexta is a small molecule designed to selectively bind and inhibit the BCL-2 protein, which plays an important role apoptosis (programmed cell death). Overexpression of the BCL-2 protein in CLL has been associated with resistance to certain therapies. It is believed that blocking BCL-2 may restore the signaling system that tells cells, including cancer cells, to self-destruct. Venclexta is being developed by AbbVie and Roche, and is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the United States and commercialized by AbbVie (under the brand name Venclyxto) outside of the United States.

Specifically, the FDA has approved the Venclexta-Rituxan combination for the treatment of people with CLL or SLL, with or without 17p deletion, who have received at least one prior therapy.

“We are pleased that this approval makes Venclexta, a first-of-its-kind targeted therapy, available for more people with chronic lymphocytic leukemia whose disease has returned after previous treatment,” said Dr. Sandra Horning, Roche’s chief medical officer and head of global product development. “Venclexta plus Rituxan provides a new chemotherapy-free option shown to help people live longer without their disease progressing, compared to a standard-of-care therapy.”

This is primarily based on the results of the Phase 3 MURANO study, which were published online in the New England Journal of Medicine in March 2018 and presented previously at the American Society of Hematology Annual Meeting in December 2017. The results showed that a fixed duration of treatment with Venclexta plus Rituxan significantly reduced the risk of disease progression or death (progression-free survival) by 81 percent compared with bendamustine plus Rituxan, a current standard of care. Patients receiving the combination also had an overall response rate of 92 percent, compared to 72 percent in patients who received the bendamustine plus rituximab combination.

According to the companies, this pairing of therapeutics represents the first oral-based, chemotherapy-free combination in CLL that allows patients an option for fixed treatment duration.

“Venclexta now gives indicated patients a new opportunity to significantly reduce the risk of their disease progressing, compared to a current standard of care. This combination provides previously treated CLL or SLL patients with a chemotherapy-free, fixed-duration treatment, allowing patients the ability to stop treatment after approximately two years,” noted Dr. Michael Severino, executive vice president of research and development and chief scientific officer for 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.”

CLL is typically a slow-progressing cancer of the bone marrow and blood, in which types of white blood cells called lymphocytes become cancerous and multiply abnormally. In the United States, CLL accounts for more than 20,000 newly diagnosed cases of leukemia each year. SLL is closely related to CLL; however, unlike CLL, SLL cancer cells are typically found in the lymph nodes and spleen rather than the bone marrow and the blood. In the United States, approximately 5,000 cases of SLL are diagnosed annually.

AbbVie and Roche are also evaluating Venclexta for acute myeloid leukemia and for certain kinds of multiple myeloma patients. Venclexta is also being studied in combination with AbbVie’s Imbruvica (ibrutinib).