Roche May Defend Rituximab, Bevacizumab Sales With New Drug Combinations

Roche has announced positive data on 2 of its innovator oncology biologics in combination with other therapies. The combinations using rituximab (MabThera, Rituxan) and bevacizumab (Avastin) could help the Swiss drug maker to protect sales of these monoclonal antibodies in the face of oncoming biosimilar competition.

Venetoclax Plus Rituximab

On December 12, Roche announced the first results from the phase 3 MURANO study, an open-lable, international, multi-center, randomized study evaluating the efficacy and safety of venetoclax (Venclexta, Venclyxto) in combination with Roche’s rituximab compared with bendamustine in combination with rituximab.

The study included 389 patients with relapsed or refractory chronic lymphocytic leukemia (CLL). Patients receiving venetoclax plus rituximab had significantly improved progression-free survival (PFS) compared with those who received bendamustine plus rituximab; at 2 years, 84.9% of patients in the venetoclax plus rituximab arm had not experienced disease progression versus 36.3% of patients in the bendamustine plus rituximab arm. Venetoclax plus rituximab reduced the risk of disease progression or death by 81% compared to bendamustine plus rituximab (HR, 0.19; 95% CI, 0.13, 0.28; P <.0001).

No new safety signals were observed with the treatment combination. Roche plans to submit data from the MURANO study to the FDA, which has granted venetoclax plus rituximab a Breakthrough Therapy Designation for the treatment of refractory CLL.

Use of Roche’s branded rituximab in this new combination could help the Swiss drug maker to defend against the eventual introduction of a rituximab biosimilar in the US market; while no biosimilar of the top-selling drug has yet been approved in the United States, Sandoz submitted a Biologics License Application (BLA) for a rituximab biosimilar to the FDA in September 2017. In Europe, Roche already faces competition from approved biosimilars, including Truxima, Riximyo, and Rixathon.

Atezolizumab Plus Bevacizumab

On December 11, Roche announced that the phase 3 IMmotion151 study met its co-primary endpoint of investigator-assessed PFS, and demonstrated that the combination of atezolizumab (Tecentriq) and bevacizumab provided a statistically significant, clinically meaningful improvement in PFS versus sunitinib (Sutent) in patients with advanced kidney cancer whose disease expressed programmed death-ligand 1.

The study was conducted in 915 patients with inoperable, locally advanced or metastatic renal cell carcinoma who had not received prior systemic active or experimental therapy. The results of the multi-center, randomized, open-label study will be presented in 2018.

Roche’s innovator bevacizumab will face competition from Amgen and Allergan’s biosimilar, Mvasi, approved by the FDA in September 2017, once the drug is launched in the US marketplace. Mvasi is also under review by European regulators; on November 9, 2017, the biosimilar was issued a positive opinion by the European Medicines Agency’s Committee for Medicinal Products for Human Use. While it is not yet clear how deep a discount Amgen and Allergan will provide on their product, Roche could use a new indication for its originator product to insulate itself from the market impact of a less expensive bevacizumab treatment.