The drug offers a new treatment option for patients with relapsed or refractory mycosis fungoides (MF) and is the first drug to be approved for use in the treatment of Sézary syndrome (SS).
MF and SS are the most common subtypes of CTCL. MF is a mature T-cell non-Hodgkin lymphoma that presents on the skin; it is the most common subtype, accounting for 50% to 70% of cases. It is a slowly progressing form of lymphoma that can involve the skin, blood, lymph nodes, and organs and may be associated with severe infections. SS is less common and accounts for approximately 3% of CTCL cases; it is a more aggressive, leukemic form of CTCL.
"Mycosis fungoides and Sézary syndrome are rare, hard-to-treat types of non-Hodgkin lymphoma, and this approval fills an unmet medical need for these patients," said Richard Pazdur, MD, director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, in a statement. "We are committed to continuing to expedite the development and review of this type of targeted therapy that offers meaningful treatments for patients."
Mogamulizumab is a humanized monoclonal antibody directed against CC chemokine receptor 4, which is frequently expressed on leukemic cells of certain hematologic malignancies, including CTCL. It has already been approved in Japan for another rare disease, adult T-cell leukemia lymphoma.
The FDA based its approval on the results from the large phase 3 MAVORIC trial. That trial compared mogamulizumab with vorinostat (Zolinza, Merck & Co), which is an FDA-approved standard-of-care treatment for patients with CTCL. The study was conducted in the United States, Europe, Japan, and Australia. A total of 372 patients with MF and SS were randomly assigned to receive either mogamulizumab or vorinostat. The results showed that mogamulizumab demonstrated significantly superior progression-free survival (PFS) with a median of 7.6 months (95% confidence interval [CI], 5.6 - 10.2), vs 3.1 months with vorinostat (95% CI, 2.8 - 4.0; hazard ratio, 0.53; 95% CI, 0.41 - 0.69; P < .001). The confirmed overall response rate was 28% with mogamulizumab vs 5% with vorinostat (P < .001).
The results of the study were initially presented in 2017 at the annual meeting of the American Society of Hematology and were reported by Medscape Medical News at that time.
"This is the first report of a randomized phase 3 study evaluating PFS as a primary endpoint in CTCL to compare a new systemic therapy against an FDA-approved agent, utilizing the consensus comprehensive global response criteria," said lead author Youn H. Kim, MD, professor of dermatology and director of the Multidisciplinary Cutaneous Lymphoma Program at the Stanford University School of Medicine in California when the results were presented. "Mogamulizumab demonstrated significantly superior efficacy outcomes compared to vorinostat in patients with previously treated CTCL."
The most common adverse reactions (reported in ≥10% of patients) were rash, including drug eruption (35%), infusion reaction (33%), fatigue (31%), diarrhea (28%), drug eruption (24%), upper respiratory tract infection (22%), musculoskeletal pain (22%), skin infection (19%), pyrexia (17%), edema (16%), nausea (16%), headache (14%), thrombocytopenia (14%), constipation (13%), anemia (12%), mucositis (12%), cough (11%), and hypertension (10%).
The FDA has noted that serious warnings regarding treatment with this agent include the risk for dermatologic toxicity, infusion reactions, infections, autoimmune problems, and complications of allogeneic stem cell transplant.
Mogamulizumab received priority review, breakthrough therapy designation, and orphan drug designation.
Cite this: FDA Approves New Drug for Cutaneous T-Cell Lymphomas - Medscape - Aug 08, 2018.