This update applies to patients in the USA
On 9th March came the announcement that tazemetostat (Tazverik) is being voluntarily withdrawn worldwide. Ipsen, the company that markets tazemetostat, made this decision after new safety findings emerged from the ongoing SYMPHONY‑1 clinical trial, which indicated a possible increased risk of secondary blood cancers when the drug was used in a specific combination regimen (lenalidomide and rituximab, also referred to as R2).
While any change in the availability of a treatment naturally raises questions, it’s important to emphasise that this withdrawal reflects the strength of global safety systems. Many effective therapies remain available, and healthcare teams are well prepared to support people who were taking tazemetostat or who are simply seeking clarity about what this news means.
This article provides a straightforward explanation of what tazemetostat is, how and where it has been used, why it has been withdrawn, and how research into EZH2 (the biological target of tazemetostat) continues to advance in ways that may still benefit patients in the future.
Ipsen shared a statement with the FLF on this news:
What is tazemetostat?
“The SYMPHONY-1 study was designed as the confirmatory trial required to further verify its safety and efficacy. However, the emerging safety data – particularly the risk of secondary hematologic malignancies – have highlighted a safety profile that is unfavorable compared to that previously observed in clinical evaluation. While this is an extremely disappointing outcome, the safety of patients remains our priority”
What is tazemetostat?
Tazemetostat is a type of targeted therapy known as an EZH2 inhibitor. EZH2 (Enhancer of Zeste Homolog 2) is an enzyme involved in regulating how genes switch on and off. In some cancers, including about 20% of FL cases, mutations in EZH2 can help cancer cells survive and grow. Targeting EZH2 became an important research focus because blocking its activity is thought to slow or even shrink the cancer.
Where was tazemetostat approved and in use?
Tazemetostat was granted accelerated approval by the U.S. Food and Drug Administration (FDA) in 2020 for:
This approval was based mainly on response rates from early studies, with the understanding that continued approval depended on the results of a larger confirmatory trial – SYMPHONY‑1.
Since its approval, tazemetostat has been prescribed as an oral, at home treatment for people with FL who had already received several lines of therapy. This typically placed it in the third line or later part of the care pathway.
In earlier clinical trials, response rates were 69% in EZH2mutated FL (with some durable responses), and 34% in FL without the EZH2 mutation. Some individual case reports even showed complete responses in heavily pretreated patients, highlighting its potential benefit. For many patients, tazemetostat provided a much needed option when other therapies were no longer effective or suitable.
Why has tazemetostat been withdrawn?
The withdrawal stems from safety concerns identified in the SYMPHONY‑1 confirmatory trial. This trial was testing tazemetostat in combination with lenalidomide and rituximab (also referred to as R2), a commonly used treatment.
An independent safety committee found cases of secondary haematologic malignancies – essentially new blood cancers developing in some patients receiving the combination. They concluded that the risks of continuing outweighed the benefits, prompting Ipsen to withdraw the drug globally and discontinue all ongoing trials. The SYMPHONY-1 study will remain open for long-term safety follow-up of current participants, but no new patients will be enrolled.
What if I am currently taking tazemetostat?
Ipsen and regulatory agencies advise that all patients stop treatment and transition to recognised standard of care therapies. Physicians are contacting affected patients and guiding them through safe alternatives.
If you are taking tazemetostat:
How does this news affect other FL treatments?
The withdrawal of tazemetostat relates specifically to this particular medicine and the new safety information observed in one specific combination regimen during the SYMPHONY‑1 trial.
FL care includes a wide range of well established treatment options, such as antibody‑ based‑ therapies, chemotherapy combinations, immunomodulatory drugs, bispecific antibodies, and CART cell therapy. These treatments work through entirely different mechanisms from EZH2 inhibitors like tazemetostat and have their own ‑well established‑ safety profiles that are continually monitored.
What this situation does highlight is the strength of global safety systems: when new evidence emerges, even for a single drug, regulatory bodies and manufacturers act promptly to ensure patient safety and wellbeing. We encourage patients, their carers and loved ones to discuss with their healthcare teams any concerns or queries.
Conclusion
The withdrawal of tazemetostat marks an important moment in the ongoing evolution of FL research and treatment. While this chapter for one specific therapy is coming to a close, the knowledge gained from its development and from the SYMPHONY‑1 study will continue to inform future advances. FL remains an area of active scientific discovery, with many therapeutic options already available and others progressing through research pipelines. As understanding of FL biology deepens, new opportunities will continue to emerge, contributing to better and more personalised treatment strategies over time.
This article is for information purposes only, and we recommend that you speak with your healthcare team if you have any questions around suitability and regional accessibility of therapy options.
Want to learn more?
If you have any questions, please get in touch by emailing us at info@theflf.org.
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