Epizyme successfully met with the U.S. Food and Drug Administration (FDA) to bolster an upcoming submission of its oral investigational treatment tazemetostat for relapsed or resistant follicular lymphoma, with or without EZH2 activating mutations.
The pre-New Drug Application (NDA) meeting is a critical step to ensure a well-organized and readily reviewable application seeking the treatment’s approval.
Epizyme lined up with the FDA regarding the data package needed to support tazemetostat’s accelerated approval as a single-agent therapy for patients who received two or more prior therapies.
Epizyme and the agency also reached an agreement for the launch of a single confirmatory trial to secure tazemetostat’s full approval. This global, randomized trial will evaluate the combination of tazemetostat with Celgene’s Revlimid (lenalidomide) plus Roche/Biogen‘s Rituxan (rituximab) – a chemo-free treatment regimen, known as R2, approved for follicular lymphoma patients as second-line or later treatment.
The trial is expected to enroll approximately 500 relapsed or refractory follicular lymphoma patients, with and without EZH2 mutations.
“We are very pleased with the outcome of our recent pre-NDA meeting and the continued alignment with FDA on our registration strategy for FL [follicular lymphoma] patients, regardless of their EZH2 status, who have received at least two prior systemic therapies,” Shefali Agarwal, MD, chief medical officer of Epizyme, said in a press release.
“FL remains an incurable disease, and we believe strongly in the potential of tazemetostat to make a difference for these patients. We are on track to submit our FL NDA for accelerated approval … and look forward to continuing to engage with [the] FDA as we work to bring tazemetostat to both FL and epithelioid sarcoma patients in the U.S. next year.”
Tazemetostat is an oral small molecule inhibitor of EZH2, a protein overproduced in a variety of cancers that plays a key role in tumor cell proliferation. By inhibiting EZH2, tazemetostat prevents the activity of certain DNA binding proteins, which is expected to change which genes are turned “on” and “off,” reducing tumor growth.
The latest updates from Epizyme’s ongoing Phase 2 trial (NCT01897571) of single-agent tazemetostat for follicular lymphoma will serve as the basis for the planned NDA submission.
Data from the study, presented at the 2019 American Society of Hematology (ASH) Annual Meeting in Orlando, are showing promising results, particularly in patients with mutations in the EZH2 gene.
Among patients with normal versions of the EZH2 gene, 34% responded to treatment, including 6% complete responses, and an additional 30% attained stable disease, to a total clinical benefit rate of 64%. Responses lasted a median of 13 months and patients remained alive and without signs of disease progression for a median of 5.7 months.
For the 43 patients with EZH2 activating mutations, 33 (77%) responded to tazemetostat, including three (6%) with complete responses. Stable disease was achieved by the remaining 23% of patients, leading to a clinical benefit rate of 100%. While data on duration of response and progression-free survival are still maturing in this group, they are currently at 8.3 months and 11.1 months, respectively.
The treatment has shown promising anti-tumor activity and a well-tolerated safety profile in early clinical trials for patients with blood and solid cancers. Several trials are currently studying tazemetostat, alone or in combination with other agents, to treat different types of cancer in adults and children. The agent received a Fast Track Designation by the FDA as a potential treatment for follicular lymphoma in 2017.
“Over the course of 2019, we’ve made significant progress building out critical functions, advancing and expanding tazemetostat development, and continuing our evolution toward becoming a commercial company,” said Robert Bazemore, Epizyme’s president and CEO.