Regulatory Decision Summary for Gazyva

Authorization was based on the findings from a multicenter, open-label, randomized phase 3 trial, Study BO21223 (GALLIUM). Patients with previously untreated advanced FL (n=1202) were randomly assigned in a 1:1 ratio to treatment with Gazyva plus chemotherapy (G-chemo) or rituximab plus chemotherapy (R-chemo).

The primary efficacy endpoint was progression-free survival (PFS) as assessed by an independent review committee. At a median follow-up of 41 months, a 28% reduction in risk of disease progression was demonstrated favoring the G-chemo arm (HR = 0.72, 95% CI: 0.56 - 0.93). The outcome is considered clinically meaningful.

The safety findings from the GALLIUM study were generally consistent with those from previous trials of Gazyva in combination with chemotherapy. The most common adverse events (AEs) reported at a higher incidence in the Gazyva arm included infusion reactions, neutropenia, upper respiratory tract infection, cough, constipation and diarrhea. Overall, the Gazyva arm had higher incidences of serious AEs compared to the rituximab arm (50% vs. 43%), Grade ≥ 3 AEs (79% vs. 72%) and fatal infections (2% vs. < 1%). The most common Grade ≥ 3 AEs observed more frequently with obinutuzumab were neutropenia, febrile neutropenia, thrombocytopenia, and infusion reactions. Patients treated with bendamustine had higher incidences of serious and fatal infections than those who received CHOP or CVP.

Most of the treatment related toxicity was managed with dose delay or discontinuation of treatment, and treatment of symptoms; or mitigated with prophylactic treatments and close monitoring. Based on the safety data submitted, the Gazyva Product Monograph has been updated to provide further information and recommendations to mitigate the known risks associated with Gazyva. The overall benefit risk profile of Gazyva in the treatment of patients with previously untreated advanced FL is considered to be positive.