NMPA Grants Conditional Approval to Tazemetostat for EZH2-Mutant R/R Follicular Lymphoma

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Tazemetostat (Tazverik) has been granted conditional approval by China’s National Medical Products Administration (NMPA) for the treatment of adult patients with relapsed or refractory EZH2-mutated follicular lymphoma who have received 2 or more prior systemic therapies.1

This regulatory decision was supported by findings from a multicenter, open-label, phase 2 bridging study (NCT05467943) conducted in China, as well as findings from clinical trials conducted outside of China.

“This approval represents a significant advancement in the management of this challenging disease,” Junning Cao, MD, of Fudan University Shanghai Cancer Center in China, the lead principal investigator of the bridging study, stated in a news release. “The majority of patients [with follicular lymphoma] experience multiple relapses over their lifetime, posing substantial treatment difficulties and often leading to poor outcomes. [Tazemetostat] has demonstrated promising efficacy in patients harboring EZH2 mutations in clinical trials. We are eager to provide this transformational epigenetic therapy to patients in China who have long sought new effective treatment options.”

This regulatory decision is the first nationwide regulatory approval of tazemetostat in China, and the drug is the first and only EZH2 inhibitor to be approved by the NMPA, according to a news release.

The bridging trial that supported this approval enrolled 42 patients at least 18 years of age with histologically confirmed relapsed/refractory follicular lymphoma with at least 1 measurable lesion; a life expectancy of at least 12 weeks; an ECOG performance status of 0 to 2; and adequate bone marrow, renal, and hepatic function.2,3 Patients were excluded if they had received prior tazemetostat or other EZH2 inhibitors; had invasion of lymphoma to the central nervous system or pia mater; had previous bone marrow malignancies; or had abnormalities associated with myelodysplastic syndromes and myeloproliferative neoplasms.3

Patients were stratified by EZH2 mutation status (mutant vs wild-type). All patients received tazemetostat at 800 mg twice daily, administered in continuous 28-day cycles, with a suggested interval of 12 hours between doses.

Overall response rate (ORR) among patients with relapsed/refractory EZH2-mutated follicular lymphoma served as the trial’s primary end point. Key secondary end points included overall survival (OS), safety, and pharmacokinetics among patients with EZH2 wild-type relapsed/refractory follicular lymphoma.

“We are thrilled to be able to bring this innovative EZH2 inhibitor to patients in China,” Michael Shi, MD, PhD, head of R&D and chief medical officer of HUTCHMED, added in the news release.1 “This approval highlights our dedication to addressing unmet medical needs not only through our internal pipeline, but also through partnering. It also marks our first approval in hematological malignancies, unveiling a new chapter for HUTCHMED as we extend our footprint into this disease area. As we move forward, we are dedicated to making this product available to patients [with relapsed/refractory follicular lymphoma] as soon as possible and will continue striving to make a meaningful impact on the lives of more patients suffering from devastating diseases.”

Notably, in 2020, the FDA approved tazemetostat for the treatment of patients with EZH2-mutated relapsed/refractory follicular lymphoma who have received at least 2 prior therapies, as well as those with relapsed/refractory follicular lymphoma who have no other available satisfactory treatment options.4 The agent is also approved by the Japan Ministry of Health, Labour and Welfare for certain patients with relapsed/refractory follicular lymphoma.1

The confirmatory phase 1b/3 SYMPHONY-1 trial (NCT04224493) is ongoing to validate the efficacy and safety of tazemetostat in patients with relapsed/refractory follicular lymphoma who have received at least 1 prior line of therapy. This multicenter, international, double-blind, randomized, active-controlled, 3-stage, biomarker-enriched trial will assign patients to receive tazemetostat or placebo, each in combination with rituximab (Rituxan) and lenalidomide (Revlimid). The primary end points are identification of the recommended phase 2 dose of tazemetostat plus lenalidomide and rituximab, as well as progression-free survival in the EZH2-mutant and wild-type populations. Secondary end points include pharmacokinetics, complete response (CR) rate, ORR, OS, duration of response, duration of CR, disease control rate, safety, and quality of life.

References

1. HUTCHMED announces NMPA conditional approval for Tazverik (tazemetostat) for the treatment of relapsed or refractory follicular lymphoma. News release. HUTCHMED (China) Limited. March 21, 2025. Accessed March 21, 2025. https://www.hutch-med.com/tazverik-nmpa-approval-follicular-lymphoma/
2. HUTCHMED completes patient enrollment of a bridging study of tazemetostat in patients with relapsed/refractory follicular lymphoma in China. News release.HUTCHMED (China) Limited. September 12, 2023. Accessed March 21, 2025.https://www.hutch-med.com/tazemetostat-bridging-study-completes-enrollment/
3. Tazemetostat for the treatment of relapsed/​refractory follicular lymphoma. ClinicalTrials.gov. Updated February 28, 2025. Accessed March 21, 2025. https://clinicaltrials.gov/study/NCT05467943
4. FDA granted accelerated approval to tazemetostat for follicular lymphoma. FDA. June 18, 2020. Accessed June 18, 2020. https://www.fda.gov/drugs/fda-granted-accelerated-approval-tazemetostat-follicular-lymphoma
5. A study to assess the efficacy, safety, pharmacodynamics, and pharmacokinetics of tazemetostat in combination with lenalidomide plus rituximab versus placebo in combination with lenalidomide plus rituximab in adult patients at least 18 years of age with relapsed/​refractory follicular lymphoma. (SYMPHONY-1). ClinicalTrials.gov. February 28, 2025. Accessed March 21, 2025. https://clinicaltrials.gov/study/NCT04224493