Valemetostat has the potential to become the world's first dual EZH1/EZH2 inhibitor to receive regulatory approval for the treatment of relapsed/refractory adult T-cell leukemia/lymphoma (ATL).

Adult T-cell leukemia/lymphoma (ATL) (Image source: imagebank.hematology.org)

January 20, 2022 /Bio Valley BIOON/--Daiichi Sankyo recently announced that it has submitted a New Drug Application (NDA) for valemetostat to the Japanese Ministry of Health, Labour and Welfare (MHLW), the drug It is a potential first-in-class dual inhibitor of EZH1 and EZH2 for the treatment of patients with relapsed/refractory adult T-cell leukemia/lymphoma (ATL). Valemetostat has the potential to become the world's first dual EZH1 and EZH2 inhibitor to receive regulatory approval and will provide a novel targeted therapy option for patients with relapsed or refractory ATL.

ATL is a rare aggressive peripheral T-cell lymphoma (PTCL) with a high incidence in parts of Japan and elsewhere. Currently, the prognosis of patients with ATL is poor. Nearly 90% of patients relapse after completing intensive first-line therapy, when few options are available.

Valemetostat is a potent, selective, small molecule inhibitor designed to combat epigenetic dysregulation by targeting EZH1 and EZH2 enzymes. Currently, valemetostat is being developed for the treatment of relapsed or refractory ATL, peripheral T-cell lymphoma (PTCL), and non-Hodgkin lymphoma (NHL). Previously, valemetostat has been granted orphan drug designation (ODD) for the treatment of PTCL by the US FDA, ODD for the treatment of ATL and SAKIGAKE (innovative drug) designation for the treatment of PTCL by the Japanese MHLW.

Chemical formula of valemetostat (Image source: selleckchem.com)

This NDA is based on results from a pivotal Phase 2 clinical study. Data were presented at the 2021 American Society of Hematology (ASH) annual meeting in Japanese patients with 3 aggressive subtypes of relapsed or refractory ATL.

The results showed that the study met its primary endpoint: an objective response rate (ORR) of 48% among 25 patients with relapsed/refractory ATL, as assessed by the Independent Efficacy Evaluation Committee. Among them, 5 had complete remission (CR), 7 had partial remission (PR), and 10 had stable disease (SD). At a median follow-up of 6.5 months, the median duration of response (DOR) had not been reached (95% CI: 1.87 months - not reached [NR]).

valemetostat clinical data

Adult T-cell leukemia/lymphoma (ATL) is a rare, aggressive peripheral T-cell lymphoma (PTCL) caused by human T-cell lymphotropic virus type 1 (HTLV-1). Globally, more than 3000 new cases of ATL are diagnosed each year. The incidence of ATL is higher in areas where the HTLV-1 virus is endemic, including southwestern Japan, Central and South America, and central Australia. Cases have also been observed in North America and Europe. The incidence of ATL is also rising in non-endemic areas. In Japan, there are about 1000 new cases of ATL and more than 1000 deaths of ATL patients each year.

Compared with other types of PTCL, ATL has the worst prognosis, with a 5-year overall survival rate of approximately 14%. The reported median survival time of patients with the most common acute ATL subtype in Japan is approximately 8 months (252 days).

Treatment of ATL is subtype-based and mainly includes intensive multi-agent chemotherapy regimens. Nearly 90% of patients relapse after completing intensive first-line therapy, when few treatment options are available. In Japan and other parts of the world, additional therapeutic approaches are urgently needed to improve the treatment outcomes of ATL. (Bioon.com)

Original source: Valemetostat New Drug Application Submitted in Japan for Treatment of Patients with Adult T-Cell Leukemia/Lymphoma