The FDA has approved Roche and AbbVie's Venclexta (venetoclax) in combination with Roche's Gazyva (obinutuzumab) for the treatment of people with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The approval follows a breakthrough therapy designation and marks a significant advancement in first-line CLL treatment options.
Clinical Trial Results Drive Approval
The approval is based on results from the phase 3 CLL14 trial, which demonstrated that the venetoclax-obinutuzumab combination achieved a significant reduction in the risk of disease worsening or death (progression-free survival) compared to Gazyva plus chemotherapy. The chemotherapy combination has served as a standard first-line therapy in this setting since receiving approval in 2013.
"Venclexta plus Gazyva is the only chemotherapy-free option of fixed duration that provides durable responses to help people live longer without progression of their disease, compared to a standard of care," said Sandra Horning, Roche's chief medical officer.
Market Impact and Patient Population
While Venclexta already has a fairly broad label in the relapsed/refractory CLL population, the previously-untreated patient group represents another 20,000 or so potential patients in the US alone, according to Horning. This expansion significantly broadens the drug's addressable market.
Roche co-markets Venclexta in the US with AbbVie, with AbbVie selling it independently elsewhere as Venclyxto. The drug represents a key growth product for both companies, generating $344 million in sales worldwide last year—more than double its turnover in the previous year—and $124 million in the last quarter. AbbVie projects sales this year to more than double once again to $725 million.
Treatment Advantages and Cost Effectiveness
Venetoclax offers distinct advantages over competing therapies, particularly regarding treatment duration. According to Peter Hillmen, professor of explorational oncology at the University of Leeds, venetoclax has an advantage over Imbruvica (ibrutinib) in that treatment can be stopped after around two years at maximum or until disease progression.
"The thing is with venetoclax is that we stop treatment. With ibrutinib, that carries on indefinitely," Hillmen explained. "The fact we have a fixed term of administration makes it more cost effective. The aim of future combinations is to try and shorten the treatment. It might cost more in the first few months, but then it becomes much more cost-effective."
Safety Considerations
In March, questions were raised over Venclexta's safety after a higher proportion of deaths was observed in patients receiving it for multiple myeloma in a trial's control arm. This led AbbVie and Roche to stop recruiting patients for all multiple myeloma trials involving the drug.
AbbVie clarified that the action does not impact any of the approved indications for venetoclax and is limited to investigational clinical trials in multiple myeloma. The company stated it "remains confident in the benefit/risk profile of venetoclax in those approved indications."
Future Development Pipeline
AbbVie continues testing Venclexta in combination with Imbruvica as another chemotherapy-free option, as well as triple therapy combining the drug with both Imbruvica and Gazyva. The company is also conducting trials for multiple myeloma, non-Hodgkin lymphoma, and myelodysplastic syndrome.
Hillmen expressed optimism about venetoclax's potential in earlier disease stages: "It is fair to say that venetoclax is a major positive development in leukemia treatment. It is leading to improved survival rates in CLL and I think as we move into first line, in patients who have not been treated, we are likely to see some better responses."
