FDA Approves Gazyva for Advanced Follicular Lymphoma

The Food and Drug Administration (FDA) has approved Gazyva (obinutuzumab) in combination with chemotherapy, followed by Gazyva alone, for the first-line treatment of patients with advanced follicular lymphoma, according to Genentech, the manufacturer of the drug.

The approval which is for patients with stage 2 bulky, 3 or 4 disease, is based on data from the phase 3 GALLIUM study, in which combining Gazyva with chemotherapy in the first-line setting reduced the risk of disease progression or death by 28 percent versus rituximab plus chemotherapy in patients with follicular lymphoma.

“Today’s Gazyva approval is an important advance for the thousands of people diagnosed each year with follicular lymphoma who hope to delay disease progression for as long as possible,” Sandra Horning, M.D., chief medical officer and head of Global Product Development at Genentech, said in a press release. “We’re pleased we can now offer patients with this incurable blood cancer an initial treatment option shown to improve upon Rituxan, the standard of care in this setting for more than 10 years.”

The international phase 3 GALLIUM study included 1,401 treatment-naive patients with indolent non-Hodgkin lymphoma, of whom 1202 had follicular lymphoma. Patients with follicular lymphoma were aged 18 years or older, had grade 1 to Iliac disease, and an ECOG performance status less than 2.

Patients were randomized to Gazyva plus chemotherapy, followed by Gazyva alone (601 patients), or Rituxan (rituximab) plus chemotherapy, followed by rituximab alone (601 patients). The chemotherapy regimens used were CHOP, CVP, or bendamustine, based on the discretion of the physicians at each study location.

Patients specifically received rituximab at 375mg/m2 on day one of each cycle or Gazyva at 1000 mg on days one, eight and 15 of cycle one and day one of subsequent cycles, for either eight 21-day cycles (CHOP and CVP) or six 28-day cycles (bendamustine). Among patients randomized to chemotherapy, 57.1 percent, 33.1 percent and 9.8 percent, received bendamustine, CHOP and CVP, respectively.

The primary endpoint of the study was progression-free survival (PFS). Secondary outcome measures included response rate, overall survival, disease-free survival, and safety. The study was unblinded per the recommendation of an independent data monitoring panel in January 2016 after a preplanned interim efficacy analysis.

The overall response rate was 91 percent in the Gazyva arm and 88 percent in the control arm. Complete remission rates were 28 percent and 27 percent, respectively.

Safety data from the 41.1-month follow-up showed that the most common grade 3/5 adverse events that occurred more often in the Gazyva arm compared to the rituximab arm were neutropenia (46.7 percent vs 39.5 percent), infections (20.3 percent vs 16.4 percent), infusion-related reactions (12.4 percent vs 6.7 percent), thrombocytopenia (6.1 percent vs 2.7 percent), second malignancies (4.7 percent vs 2.7 percent) and cardiac events (3.9 percent vs 2.8 percent).

Gazyva is a glycoengineered antibody against CD20. Through the glycoengineering process, sugar molecules are removed from immune-effector antibody cells in the posttranslational setting, significantly impacting antigen binding and function. Specifically, Gazyva is designed to lack fucose molecules.

The FDA previously approved Gazyva for use in combination with bendamustine for patients with follicular lymphoma who have received prior therapy.