Japan Green Lights Valemetostat Tosilate for Relapsed/Refractory Adult T-cell Leukemia/Lymphoma

Sep 26, 2022

The Japan Ministry of Health, Labor and Welfare has approved valemetostat tosilate for the treatment of patients with relapsed or refractory adult T-cell leukemia/lymphoma.

Wataru Takasaki, PhD

Wataru Takasaki, PhD

The Japan Ministry of Health, Labor and Welfare (MHLW) has approved valemetostat tosilate (Ezharmia; DS-3201b) for the treatment of patients with relapsed or refractory adult T-cell leukemia/lymphoma (ATL).1

The regulatory decision was based on results from a pivotal phase 2 trial (NCT04102150) conducted in Japanese patients with 3 aggressive subtypes of relapsed/refractory ATL that showed the novel, potent, and selective EZH1/EZH2 dual inhibitor had therapeutic efficacy in this population.

Patients treated with valemetostat tosilate (n = 25) achieved an objective response rate (ORR) of 48% (95% CI, 27.8%-68.7%). The complete response rate was 20% with a partial response rate of 28%.

“As the first dual inhibitor of EZH1 and EZH2 to receive regulatory approval anywhere in the world, [valemetostat tosilate] represents an important advancement in the treatment of patients with relapsed or refractory ATL, who have very few options beyond intensive chemotherapy,” Wataru Takasaki, PhD, executive officer and head of R&D Division in Japan, Daiichi Sankyo.

“We are proud to have successfully translated the science behind dual EZH1 and EZH2 inhibition into a new and novel therapy for these patients, who face a poor prognosis and represent one of the most significant unmet medical needs in Japan. We will continue to pioneer the approach in the global development of [valemetostat tosilate], our fifth new oncology medicine approved in Japan in the past 3 years.”

Nearly 90% of patients with ATL relapse following first-line therapy. At present, there are few treatment options available in later-line settings.

The open-label, multi-center, single-arm phase 2 trial evaluated efficacy and safety of valemetostat tosilate monotherapy in patients who were at least 20 years old with relapsed/refractory ATL who were previously treated with mogamulizumab or at least one systemic chemotherapy in case of intolerance/contraindication for mogamulizumab.2 Patients were also required to have an ECOG performance status of 0 to 2 and a life expectancy of at least 3 months.

Key exclusion criteria included the presence of central nervous system involvement at the time of screening tests, poorly controlled complications, an uncontrolled infection, the use of corticosteroids over 10 mg/day, prior receipt of allogeneic hematopoietic stem cell transplantation, or a history of or concurrent malignant tumors.

Enrolled patients received 200 mg of oral valemetostat tosilate once daily. The primary end point of the trial was ORR assessed by independent efficacy assessment committee. Secondary end points included investigator-assessed ORR, best response in tumor lesions, complete remission rate, tumor control rate, time to response, duration of response, progression-free survival, overall survival, and safety.

Regarding safety, 96% of patients experienced drug-related, treatment-emergent adverse effects (TEAEs). The most common TEAEs included decreased platelet count (80%), anemia (44%), alopecia (40%), dysgeusia (36%), decreased lymphocyte count (20%), decreased neutrophil count (20%), and decreased white blood cell count (20%).

In December 2021, the FDA granted an orphan drug designation to valemetostat tosilate for the treatment of patients with peripheral T-cell lymphoma.


  1. Ezharmia® approved in Japan as first dual EZH1 and EZH2 inhibitor therapy for patients with adult T-cell leukemia/lymphoma. News release. Daiichi Sankyo. September 26, 2022. Accessed September 26, 2022. https://bit.ly/3UDhrHh
  2. Valemetostat tosilate (DS-3201b) phase 2 study in relapsed or refractory adult T-cell leukemia/lymphoma. ClinicalTrials.gov. Updated January 12, 2022. Accessed September 26, 2022. https://clinicaltrials.gov/ct2/show/NCT04102150
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