Remetinostat for the treatment of cutaneous T-cell lymphoma (CTCL)


Cutaneous T-cell lymphoma (CTCL) is a rare form of blood cancer that presents initially in the skin and is classified as an orphan disease. Remetinostat is expected to be an important additional treatment option for patients who suffer from this cancer, and the dermatologists who treat them.

Mechanism of Action

According to the US National Cancer Institute mycosis fungoides (MF) is the most common type of CTCL. Remetinostat is a novel histone deacetylase inhibitor (HDAC) that Medivir develops for topical use for the treatment of early-stage MF/CTCL. It was designed to be effective in the skin in order to treat the disease, but to be rapidly broken down and inactivated in blood, in order to limit the adverse effects associated with systemically administered HDAC inhibitors.

Disease area

CTCL is an orphan disease in both the US and Europe. The annual incidence is 1,000-3,000 and has an estimated prevalence in the US of ~20,000, with similar numbers of patients in EU5. Approximately 75% of CTCL patients have early stage (IA-IIA) disease. In the early stages of CTCL the disease is confined to the skin and is predominantly indolent, with most patients remaining in this stage of disease for many years. While disease progression is slow for most patients with early-stage CTCL, their tumours result in significant morbidity and quality of life issues, including clinically significant pruritus (itch). Since they remain in this stage for an extended period they usually require long-term treatment. The 1st line of treatment for these patients is topical steroids of increasing strength. 2nd line treatment options are limited once steroids become ineffective, or when their side effects become limiting. The second-line options lack sustained efficacy and/or tolerability and are often highly irritating. Consequently there is a substantial level of unmet need in patients whose lesions are not responding to current therapy or who continue to experience side effects like clinically significant pruritus, especially for continuous and extended treatment over large lesion areas. Remetinostat is expected to have the potential to capture a significant market share based on its clinical profile balancing efficacy, safety and tolerability.

Project overview

Positive top line data from the phase II study in early-stage CTCL patients were reported in April 2017 and further results were presented at the EORTC Cutaneous Lymphoma Task Force Meeting on October 15. Patients in the remetinostat gel 1% twice-daily arm had highest proportion of confirmed responses (8/20, 40%). Remetinostat also demonstrated an effect on itching (pruritus), a key symptom associated with CTCL. The remetinostat 1% twice-daily arm gave rise to an 80% rate of clinically significant reductions in the subgroup of patients with clinically significant itching at baseline. Across all three dose groups, topical remetinostat was well-tolerated and without signs of systemic adverse effects, including those associated with systemic HDAC inhibitors. Based on these results, Medivir expects to initiate discussions with regulatory authorities to initiate a phase III study thereafter. In September 2017 Medivir signed a clinical trial agreement with Stanford University to provide remetinostat gel for an investigator-initiated study of remetinostat to be conducted in patients with basal cell carcinoma. Further information on this study can be found at with the identifier NCT03180528.


Remetinostat is a novel inhibitor being developed for topical use for the treatment of CTCL.


Facts and figures

  • Gene expression can be regulated by non-heritable (epigenetic) modifications of DNA, including acetylation of histones. HDAC enzymes regulate this epigenetic process by removing these acetylations from histones, and causing subsequent changes in gene expression that lead to altered cellular differentiation and anti-tumour effects.
  • HDAC inhibitors have been approved for the treatment of late-stage CTCL, demonstrating the proof of concept of this mechanism of action. However, they cause a range of systemic toxicities that mean they cannot be used in early-stage disease. Thus there is a clear opportunity for remetinostat to provide benefit to early stage CTCL patients who cannot be treated with these systemic HDAC inhibitors.
  • In the US the expected addressable market for early-stage CTCL is $900 million
  • The early stages of the disease is confined to the skin:
  • Stage IA involves <10% of skin
  • Stage IB involves >10% of skin
  • Stage IIA has stage IA or B skin involvement with additional limited involvement of lymph nodes

Page updated 6 November 2017