Ipsen Voluntarily Withdraws Tazemetostat From All Markets Following Safety Signal in Confirmatory Trial

Ipsen announced that it is voluntarily withdrawing tazemetostat (Tazverik; Ipsen) from all indications across all markets, effective immediately. The decision was driven by emerging safety data from the ongoing phase 1b/3 SYMPHONY-1 trial (NCT04224493), which was designed to serve as the confirmatory study required under tazemetostat’s accelerated approval pathway.¹

Tazemetostat, an oral inhibitor of the epigenetic enzyme enhancer of zeste homolog 2 (EZH2), received FDA accelerated approval in January 2020 for adults and adolescents aged 16 years and older with metastatic or locally advanced epithelioid sarcoma (ES) not eligible for complete resection. A second accelerated approval followed in June 2020 for adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) whose tumors harbor an EZH2 mutation and who had received at least 2 prior systemic therapies, as well as for those with R/R FL who had no satisfactory alternative treatment options.² Both approvals were based on overall response rate and duration of response from single-arm trials, with continued approval contingent on confirmatory evidence of clinical benefit.²

Why Did Ipsen Withdraw Tazemetostat?

SYMPHONY-1 was evaluating tazemetostat in combination with lenalidomide (Revlimid; Bristol Myers Squibb) and rituximab (Rituxan; Genentech; R2) vs R2 alone as second-line therapy in R/R FL across 229 sites in 15 countries. The trial’s independent data monitoring committee identified a pattern of adverse events involving secondary hematologic malignancies and concluded that the risks of the tazemetostat-containing regimen may outweigh its potential benefits.¹ Notably, an increased risk of secondary malignancies, including T-cell lymphoblastic lymphoma, myelodysplastic syndrome, and acute myeloid leukemia, has been recognized as a known warning in the drug’s prescribing information since its initial approval.³

Prior research had also explored tazemetostat combinations, including an investigation of the agent with lenalidomide and rituximab, which informed the design of SYMPHONY-1.³

"While this is an extremely disappointing outcome, the safety of patients remains our priority," said Christelle Huguet, PhD, executive vice president and head of research and development at Ipsen. "Emerging data from this confirmatory study have highlighted a safety profile that is unfavorable compared to that previously observed in clinical evaluation. We will now work closely with investigators and clinical teams to support patients through the respective next steps and transition plans."¹

Questions Surrounding EZH2 Inhibitor Class Safety

"This notable safety finding may raise questions on how to balance the use of the accelerated approval pathway for agents that may increase the risk for secondary hematologic malignancies, as well as the mechanism by which tazemetostat or other EZH2 [mevrometostat] and EZH1/2 inhibitors [eg, valmetostat, tulmimetostat] may increase the risk of secondary hematologic malignancies when used in combination with other agents, in this case notably when combined with lenalidomide and rituximab, of which lenalidomide has been noted to increase the risk for secondary primary malignancies," said Matthew Lei, PharmD, BCOP, clinical pharmacy specialist at Massachusetts General Hospital.

In addition to the market withdrawal, Ipsen has halted treatment for all patients currently enrolled in SYMPHONY-1. Participants will continue on lenalidomide plus rituximab alone, and the trial will remain open without further enrollment to allow for long-term safety follow-up. All other active tazemetostat clinical trials and expanded access programs are also being discontinued. Ipsen is coordinating with the FDA on the steps required to formally execute the withdrawal.

Pharmacist Implications

The immediate withdrawal of tazemetostat carries significant practice-level implications for pharmacists across oncology, specialty, and health-system settings. Pharmacists should promptly verify whether any patients at their institution or within their specialty pharmacy are currently receiving tazemetostat and work with the oncology care team to facilitate urgent transitions to alternative therapies.

Patients who received tazemetostat should be made aware of the importance of continued long-term monitoring for secondary malignancies, consistent with the warnings that were present in the drug’s original prescribing information.³ Any unused medication should be returned or disposed of in accordance with institutional and FDA guidance. Pharmacists who manage specialty drug inventories should remove tazemetostat from formularies and update clinical decision support tools, prior authorization criteria, and dispensing protocols accordingly.

REFERENCES

1. Ipsen voluntarily withdraws Tazverik (tazemetostat) in follicular lymphoma and epithelioid sarcoma. News release. Ipsen. Published March 9, 2026. Accessed March 9, 2026. https://www.ipsen.com/press-release/ipsen-voluntarily-withdraws-tazverik-tazemetostat-in-follicular-lymphoma-and-epithelioid-sarcoma-3251503/

2. Antrim A. Tazemetostat receives FDA accelerated approval for relapsed/refractory follicular lymphoma. Pharmacy Times. Published June 19, 2020. Accessed March 9, 2026. https://www.pharmacytimes.com/view/tazemetostat-receives-fda-accelerated-approval-for-relapsedrefractory-follicular-lymphoma

3. Batlevi CL, Salles G, Park SI, et al. Tazemetostat in combination with lenalidomide and rituximab in patients with relapsed/refractory follicular lymphoma: phase 1b results of Symphony-1. Blood. 2022;140(supp 1):2296-2298. doi:10.1182/blood-2022-166991