FDA Grants Fast Track Status to SETD2 Inhibitor EZM0414 for Relapsed/Refractory DLBCL


The FDA granted a fast track designation to EZM0414, a first-in-class, oral SETD2 inhibitor, for use as a potential therapeutic option in adult patients with relapsed or refractory diffuse large B-cell lymphoma.



The FDA has granted a fast track designation to the first-in-class, oral SETD2 inhibitor, EZM0414, for use as a potential therapeutic option in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), according to an announcement made by Epizyme, Inc.1

The FDA Fast Track Program was developed to enable the development of critical novel agents and to provide access to patients more rapidly. Fast track designation allows for early and frequent communication between the regulatory agency and a product sponsor throughout the developmental and review process.

The safety of the agent is under evaluation in a recently initiated phase 1/1b study. Investigators will also identify the optimal dose of EZM0414. After the dose-ranging phase of the research, the study will be expanded to evaluate the drug in the following 3 patient cohorts: those with t(4;14) multiple myeloma, non-t(4;14) multiple myeloma, and DLBCL.

“Today we are excited to announce an important milestone for Epizyme, as we prepare to bring another investigational candidate into the clinic with the initiation of this first-in-human clinical trial of our SETD2 inhibitor, EZM0414,” Grant Bogle, president and chief executive officer at Epizyme, stated in a press release. “As leaders in pioneering therapies against novel epigenetic targets, bringing EZM0414 to the clinic is an important advancement as we strive to fulfill our vision of making transformative therapies a reality for patients living with cancer.”

Data previously presented during the 2021 EHA Congress showed that a selective SETD2 inhibitor possessed properties for in vitro and in vivo use.2 Preclinical findings have showcased the successful pharmacologic targeting of the underlying oncogenic mechanism that is driven by MMSET overexpression and demonstrates SETD2 as an oncogenic driver in multiple myeloma.

Moreover, in xenograft models, SETD2 inhibition demonstrated strong tumor growth inhibition in both t(4;14) and non-t(4;14) multiple myeloma. Collectively, preliminary in vitro findings showed that single-agent activity of SETD2 inhibition could be enhanced by pairing this kind of agent with standard-of-care treatments and emerging options in the multiple myeloma paradigm.

“The receipt of fast track designation underscores the urgent need for innovative therapies that may significantly improve the lives of patients living with devastating diseases such as DLBCL,” Shefali Agarwal, MD, executive vice president and chief medical and development officer at Epizyme, stated in a press release. “Additionally, through the initiation of our phase 1/1b study, we look forward to evaluating the safety and efficacy of EZM0414 in both DLBCL and multiple myeloma, including high-risk t(4;14) multiple myeloma…We believe the inhibition of SETD2 may play an important role in treating these patients.”


  1. Epizyme receives fast track designation from US FDA and announces initiation of phase 1/1b study of its novel SETD2 inhibitor EZM0414. News release. Epizyme, Inc. November 4, 2021. Accessed November 4, 2021. https://bit.ly/2ZTnYWa
  2. Totman J. Discovering of a selective inhibitor of the SETD2 histone methyltransferase with potent in vitro and in vivo activity in preclinical models of multiple myeloma. Presented at: 2021 EHA Congress; June 14, 2021; virtual. https://bit.ly/3BNaHfk
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