Genentech, a member of the Roche Group, announced that the FDA has accepted the company’s supplemental Biologics License Application (sBLA) and granted Priority Review for Gazyva (obinutuzumab) in combination with chemotherapy followed by Gazyva alone for people with previously untreated follicular lymphoma, one of the most common blood cancers among adults. Follicular lymphoma, a slow-growing (indolent) form of non-Hodgkin’s lymphoma, is incurable and characterized by cycles of remission and relapse.
“Follicular lymphoma becomes harder to treat each time it returns, and the goal of initial treatment is to prevent the cancer from progressing for as long as possible,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “Based on the GALLIUM study, Gazyva-based treatment significantly improved progression-free survival over the current standard of care, and we are committed to bringing this potential new option to patients as soon as possible.”
The sBLA is based on results of the GALLIUM study, which is the first phase III study in previously untreated follicular lymphoma to show superior progression-free survival (PFS) over Rituxan® (rituximab)-based treatment, the current standard of care. Adverse events (AEs) with either Gazyva or Rituxan were consistent with those seen in previous studies.
The FDA is expected to make a decision on approval under Priority Review by December 23, 2017. Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the safety and effectiveness of the treatment, prevention or diagnosis of a serious disease. Additional submissions of the GALLIUM data to health authorities around the world are ongoing.
GALLIUM (NCT01332968) is a global phase III open-label, multicenter, randomized two-arm study examining the efficacy and safety of Gazyva plus chemotherapy followed by Gazyva alone for up to two years, as compared head-to-head against Rituxan plus chemotherapy followed by Rituxan alone for up to two years. Chemotherapies used were CHOP, CVP or bendamustine and were selected by each participating study site prior to beginning enrollment. GALLIUM included 1,401 patients with previously untreated indolent non-Hodgkin’s lymphoma (iNHL), of which 1,202 patients had follicular lymphoma. The primary endpoint of the study was investigator-assessed progression-free survival (PFS) in patients with follicular lymphoma, with secondary endpoints including PFS assessed by independent review committee (IRC) in patients with follicular lymphoma, PFS in the overall study population (iNHL), response rate (overall response, ORR; and complete response, CR), overall survival (OS) and safety. The study is being conducted in cooperation with the GLSG (Germany), the East German Study Group Hematology and Oncology (OSHO; Germany) and the NCRI (United Kingdom). Results after a follow-up period of 41.1 months showed:
Gazyva-based treatment reduced the risk of disease worsening or death (PFS, as assessed by investigator) by 32% compared to Rituxan-based treatment (HR=0.68; 95% CI 0.54-0.87; p=0.0016).
IRC-assessed PFS was consistent with investigator-assessed PFS. As assessed by IRC, Gazyva-based treatment reduced the risk of disease worsening or death by 28% compared to Rituxan-based treatment (HR=0.72; 95% CI 0.56-0.93; p=0.0018). Median PFS has not yet been reached in either treatment arm.
The most common Grade 3-5 AEs that occurred more often in the Gazyva arm compared to the Rituxan arm were low white blood cell count (neutropenia, 46.7% vs. 39.5%), infections (20.3% vs. 16.4%), infusion-related reactions (IRRs, 12.4% vs. 6.7%), low platelet count (thrombocytopenia, 6.1% vs. 2.7%), new tumors (second malignancies, 4.7% vs. 2.7%) and cardiac events (3.9% vs. 2.8%).
GALLIUM is the third positive phase III study for Gazyva, following the CLL11 study in patients with previously untreated chronic lymphocytic leukemia (CLL) and the GADOLIN study in patients with indolent (slow-growing) non-Hodgkin’s lymphoma whose disease progressed during or within six months of prior Rituxan-based therapy.