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


Cutaneous T-cell lymphoma (CTCL) is 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

Remetinostat is a novel histone deacetylase inhibitor (HDAC) being developed for topical use for the treatment of CTCL. It was designed to be active 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 systemic exposure to 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

A successful Phase I study of remetinostat was completed, in which 28 days of dosing with the drug was shown to be safe and well-tolerated and have an encouraging efficacy profile with an overall response rate of 28% compared to 0% in the placebo arm. Furthermore biopsy samples showed increases in levels of lysine acetylation in the skin of treated patients. An open-label phase II study of three different dose schedules of remetinostat in patients with early-stage CTCL is close to completion. Interim data from this study demonstrated an efficacy profile appropriate for early stage CTCL in a highly treatment experienced population. Furthermore remetinostat showed a very favourable safety profile, with no adverse events that are typically associated with systemic HDAC inhibitors. Planning is currently underway for Phase 3 to start in H2 2017 with a potential launch in 2021.

We are currently also exploring other indications for remetinostat where a topical HDAC inhibitor could be very beneficial to treat skin diseases caused by local immune activation.

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 15 May 2017