Tazemetostat Withdrawn From All Trials and Markets Due to Safety Concerns

Ipsen announced the voluntary withdrawal of tazemetostat (Tazverik) from all global markets and for all indications, effective immediately.¹ This decision follows a recommendation from the independent data monitoring committee (IDMC) based on emerging safety data from the phase 1b/3 SYMPHONY-1 trial (NCT04224493).² The data indicated a risk of secondary hematologic malignancies, leading to the conclusion that the risks associated with the treatment regimen may outweigh the potential benefits for patients.

In response, Ipsen, the manufacturer, is discontinuing all active tazemetostat clinical trials and expanded access programs. Patients currently enrolled in the SYMPHONY-1 trial will cease tazemetostat treatment and transition to the standard of care. Despite the withdrawal, Ipsen has stated that this action is not expected to impact the company’s current financial guidance.

The withdrawal of tazemetostat applies to all indications for which the drug was previously available, specifically follicular lymphoma (FL) and epithelioid sarcoma (ES).

Primary Driver: Safety Concerns

The decision was triggered by unfavorable safety findings in the ongoing confirmatory SYMPHONY-1 trial.

• Adverse events: The IDMC identified instances of secondary hematologic malignancies among participants.
• Risk-benefit reevaluation: Based on these emerging data, the safety profile was determined to be unfavorable compared to resultsobserved in earlier clinical evaluations.

Regulatory Context

Tazemetostat was originally granted accelerated approval by the FDA in 2020. Under the accelerated approval pathway, continued approval is often contingent upon the verification of clinical benefit in confirmatory trials. SYMPHONY-1 served as this required confirmatory trial for the follicular lymphoma indication. Ipsen is currently working with the FDA to execute the withdrawal and provide necessary clinical information.

Clinical Trial Impacts

Ipsen has initiated a comprehensive shutdown of the tazemetostat clinical development program.

The SYMPHONY-1 study evaluated tazemetostat in combination with lenalidomide and rituximab as a second-line therapy for relapsed/refractory (R/R) FL.

The study will remain open for long-term safety follow-up of existing participants, but no further enrollment will occur.

The trial involved 229 sites across 15 countries, including the US, European Union, and China.

Tazemetostat is an EZH2 inhibitor that was marketed by Ipsen in the US and available in other regions (Japan, Macau, Hong Kong, and China) via partners.

Before the withdrawal, tazemetostat was indicated adult and pediatric patients with ES, adult patients with R/R FL whose tumors are positive for an EZH2 mutation and who received at least 2 prior lines of therapy, and adult patients with R/R FL who have no satisfactory alternative treatment options.

“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, in a news release. “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.”

REFERENCES

1.Ipsen voluntarily withdraws Tazverik (tazemetostat) in follicular lymphoma and epithelioid sarcoma. News release. Ipsen. March 9, 2026. https://tinyurl.com/3zrdvyu5

2.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. Updated March 2, 2026. Accessed March 9, 2026.