NICE Suspends Resminostat Appraisal After Company Withdraws Marketing Authorization Application
核心洞察
NICE has suspended its appraisal of resminostat for maintenance treatment of advanced mycosis fungoides (搜索) or Sézary syndrome (搜索) after the company withdrew its Marketing Authorisation Application from the MHRA.
The phase II RESMAIN trial demonstrated significant clinical benefit, with resminostat extending median progression-free survival to 8.3 months compared to 4.2 months with placebo.
Despite positive trial results showing a hazard ratio of 0.62 and statistical significance (p = 0.015), the regulatory pathway for this rare lymphoma treatment has been halted.
The National Institute for Health and Care Excellence (NICE) has suspended its appraisal of resminostat for maintenance treatment of advanced mycosis fungoides (搜索) or Sézary syndrome (搜索) after the pharmaceutical company withdrew its Marketing Authorisation Application from the Medicines and Healthcare products Regulatory Agency (MHRA). The decision represents a setback for patients with these rare cutaneous T-cell lymphomas (搜索), despite promising clinical trial results.
Clinical Trial Results Support Efficacy
The suspension comes despite positive results from the phase II RESMAIN trial (NCT02953301), a multicenter, double-blind, randomized, placebo-controlled study published in The Lancet Haematology. The trial evaluated resminostat, a histone deacetylase inhibitor, as maintenance therapy in 201 adults with advanced-stage mycosis fungoides (搜索) or Sézary syndrome (搜索) who had achieved disease control after at least one prior systemic therapy or total skin electron beam treatment.
The study enrolled patients with histologically confirmed Stage IIB–IVB mycosis fungoides (搜索) or Sézary syndrome (搜索), randomizing 100 patients to resminostat maintenance and 101 to placebo. The primary endpoint was progression-free survival (PFS).
Significant Improvement in Disease Control
Results demonstrated a clinically meaningful benefit for resminostat maintenance therapy. Median PFS was 8.3 months (95% confidence interval [CI], 4.2–15.7) with resminostat compared to 4.2 months (95% CI, 2.8–6.4) with placebo, representing a hazard ratio of 0.62 (95% CI, 0.42–0.92; p = 0.015).
The overall response rate was 17% (95% CI, 10–27) with resminostat, including partial responses in 14% of patients and complete responses in 4%, compared to 10% (95% CI, 5–18) with placebo, which included partial responses in 10% of patients and no complete responses.
Safety Profile and Tolerability
The trial revealed a manageable but notable safety profile for resminostat. Grade ≥3 treatment-emergent adverse events occurred in 38% of patients receiving resminostat versus 15% with placebo, while serious adverse events occurred in 19% versus 12%, respectively.
The most common adverse events of any grade with resminostat included nausea (68%), diarrhea (44%), vomiting (32%), and fatigue (29%). These gastrointestinal and constitutional symptoms represent the primary tolerability challenges associated with the histone deacetylase inhibitor.
Regulatory Pathway Uncertainty
NICE had initially selected the appraisal for its standard technology appraisal process, recognizing the topic's importance to patients, carers, healthcare professionals, commissioners, and public health. The institute anticipated the evaluation would help ensure clinical benefit realization, address inequalities in use, and optimize NHS resource utilization.
The project, designated ID6478 and led by Danielle Lees, progressed through topic selection in August 2024 and referral in December 2024 before the January 2026 suspension. NICE has indicated it will continue monitoring developments and will update interested parties if the situation changes, leaving open the possibility of resuming the appraisal should the company decide to pursue regulatory approval in the future.