Japan's Ministry of Health, Labour, and Welfare (MHLW) has officially cleared the "all-case surveillance" post-marketing observational study requirement for Eisai's anticancer agent Remitoro® (denileukin diftitox), the company announced on May 16, 2025.
The surveillance requirement had been in place since Remitoro's approval in March 2021 for the treatment of relapsed or refractory Peripheral T-cell Lymphoma (PTCL) and Cutaneous T-cell Lymphoma (CTCL) in Japan. The condition was imposed due to the limited number of subjects in Japanese clinical trials, necessitating additional real-world safety and efficacy data.
Post-Marketing Study Results
The comprehensive post-marketing study involved 111 patients for safety analysis and 85 patients for efficacy evaluation across 86 medical facilities in Japan. Patients began treatment between May 2021 and September 2022.
The efficacy analysis showed an overall response rate of 16.5% across all evaluated cases. When broken down by lymphoma type, the response rate was 15.7% in PTCL patients (70 cases) and 20.0% in CTCL patients (15 cases).
Safety data revealed several common adverse drug reactions with incidence rates of 10% or higher:
- Aspartate aminotransferase increased (22.5%)
- Capillary leak syndrome (21.6%)
- Alanine aminotransferase increased (21.6%)
- Platelet count decreased (15.3%)
- Hepatic function abnormal (14.4%)
- Pyrexia (13.5%)
Based on these findings, the MHLW determined that the surveillance was conducted properly and that the necessary measures to ensure proper use of Remitoro were sufficient to lift the post-marketing requirement.
Mechanism of Action and Market Position
Remitoro is a fusion protein consisting of interleukin-2 (IL-2) and a partial sequence of diphtheria toxin. Its antitumor effect stems from specific binding to IL-2 receptors on the surface of tumoral lymphocytes, followed by intracellular delivery and release of diphtheria toxin fragments that inhibit protein synthesis and induce cell death.
Eisai maintains exclusive development and marketing rights for Remitoro in Japan and throughout Asia, positioning the company strategically in the treatment landscape for these rare lymphomas.
T-Cell Lymphoma Landscape in Japan
PTCL is a type of T-cell non-Hodgkin's lymphoma classified as an intermediate-grade lymphoma. It is often detected in advanced stages with symptoms including lymph node swelling, fever, night sweats, and weight loss. While ALK-positive anaplastic large cell lymphoma (occurring typically in patients in their 20s and 30s) has a favorable prognosis, other PTCL types generally affect patients around age 60 and may have poor prognoses or be difficult to treat. Japan has an estimated PTCL patient population of less than 7,000.
CTCL, another form of non-Hodgkin's lymphoma, primarily affects the skin but can manifest in additional sites like lymph nodes and peripheral blood. The disease causes skin lesions and reduces quality of life due to pain and pruritus (itching). Though generally a low-grade lymphoma with slow progression, CTCL becomes highly malignant at the tumor stage with poor prognosis. The estimated CTCL patient population in Japan is less than 4,000.
Both conditions represent areas of high unmet medical need, particularly for patients with relapsed or refractory disease.
Future Directions
Eisai has committed to continuing promotion of Remitoro's proper use and providing information about the product to healthcare professionals. The company aims to further contribute to improving benefits for patients with these challenging forms of lymphoma and their families.
The clearance of the post-marketing surveillance requirement represents an important milestone in Remitoro's lifecycle management and further establishes its position in the treatment algorithm for T-cell lymphomas in Japan.
