FDA Approves Tazemetostat for Relapsed/Refractory Follicular Lymphoma

The FDA granted an accelerated approval to tazemetostat (Tazverik) for the treatment of patients with relapsed or refractory follicular lymphoma (FL) whose tumors are EZH2-positive and have received 2 or more lines of therapy; and for adults with relapsed/refractory FL who have no other satisfactory treatment options, according to Epizyme, the manufacturer of the drug.

“We are very pleased to be able to offer TAZVERIK as a treatment option for relapsed or refractory FL patients, which is the culmination of many years of work by our team,” said Shefali Agarwal, MD, chief medical officer of Epizyme, in a press release.

The approval was based off an open-label, single-arm phase 2 trial that included patients with histologically confirmed FL that progressed after 2 or more systemic treatments. There were 45 patients with EZH2-activating mutations and 54 patients with wildtype EZH2.

Everyone enrolled was treated with 800 mg of tazemestostat twice a day. Average duration of follow-up was 22 months for patients with EZH1 mutations, and 36 months for wildtype.

Median duration of response (DOR) for the EZH2-activating mutation group was 10.9 months, while it was 13.0 months for the EZH2 wildtype patients. Overall response rates were 69% and 34% in the mutation and wildtype cohorts, respectively.

In the EZH2-activating mutation group, 12% of patients had a complete response, and 57% had a partial response. For the EZH2 wildtype group, 4% had a complete response and 30% had a partial response.

“In our view, there remains no clear standard of care in the relapsed and/or refractory FL population as not all patients benefit from today’s available therapies. Based on this label, physicians will have the ability to use their clinical discretion to prescribe TAZVERIK for their relapsed or refractory patients regardless of EZH2 mutational status and without regard to a specific line of treatment where other options are not satisfactory. We are grateful to the many patients, physicians and medical teams who helped bring us to this important achievement,” Agarwal said.

Serious adverse events (AEs) that occurred in 2% or more of patients were general physical health deterioration, abdominal pain, pneumonia, sepsis, and anemia. The most common AE, which occurred in 20% or more of patients receiving tazemetostat were fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain.

Eight percent of patients discontinued treatment because of adverse reactions, and there were no reported deaths on the study, black box warnings, or contraindications.

“Follicular lymphoma remains an incurable disease, and even with the availability of new drugs in recent years, there have remained important unmet needs in the treatment of follicular lymphoma,” concluded John P. Leonard, MD, the Richard T. Silver Distinguished Professor of Hematology and Medical Oncology at Weill Cornell Medicine, an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center, and an investigator in the Phase 1b/3 confirmatory trial for TAZVERIK for FL. “The durable responses observed with this drug are notable in the context of the safety profile and route of oral, at-home administration, and will offer an important new option for physicians as we care for patients with relapsed/refractory follicular lymphoma.”

Continued approvals for these 2 indications may be contingent on the verification and description of clinical benefit in confirmatory trials.