Gazyva Granted Priority Review for Follicular Lymphoma

Sandra Horning, MD

The Food and Drug Administration (FDA) granted a priority review to a supplemental biologics license application (sBLA) for Gazyva (obinutuzumab) to be used in combination with chemotherapy for first-line treatment of patients who have follicular lymphoma, according to Genentech, the manufacturer of the drug.

The sBLA 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 32 percent versus rituximab plus chemotherapy in patients with follicular lymphoma. Under the Prescription Drug User Fee Act, the FDA is scheduled to make a final approval decision on or before Dec. 23, 2017.

“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,” Sandra Horning, M.D., chief medical officer and head of Global Product Development at Genentech, said in a press release. “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 international phase 3 GALLIUM study included 1,401 treatment-naive patients with indolent non-Hodgkin lymphoma, of whom 1,202 had follicular lymphoma. Patients with follicular lymphoma were aged 18 years or older, had grade 1 to 3a disease, and an ECOG performance status under 2.

Patients were randomized to Gazyva plus chemotherapy, followed by Gazyva alone (601 patients), or Rituxan (rituximab) plus chemotherapy, followed by Rituxan 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 Rituxan 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 (OS), 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.

At a median follow-up of 41.1 months, the hazard ratio (HR) for PFS by investigator assessment was 0.68. Per independent review, the HR for PFS was 0.72. The median PFS has not been reached yet in either treatment arm.

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).

Data from a median follow-up of 34.5 months were presented at the 2016 ASH Annual Meeting. Those results showed that the three-year PFS rate was 80 percent in the Gazyva arm versus 73.3 percent in the rituximab arm. The three-year PFS rate was 81.9 percent in the Gazyva arm versus 77.9 percent in the Rituxan arm.

In the Gazyva arm, the overall response rate was 88.5 percent versus 86.9 percent in the Rituxan cohort. The complete remission rates were 19.5 percent versus 23.8 percent and the partial remission rates were 69.1 percent versus 63.1 percent, respectively. Ninety-two percent of patients in the Gazyva arm achieved MRD-negativity in the blood and/or bone marrow, compared with 84.9 percent in the control arm.

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.