Date: 2018-05-18
Type of
information: Presentation of results at a congress
phase: 2
Announcement: presentation of results at the International Investigative Dermatology (IID) meeting
Company: Medivir (Sweden)
Product: remetinostat
Action
mechanism:
- HDAC inhibitor. Remetinostat is a topical, skin-directed inhibitor of histone deacetylases (HDACs). The compound was designed to effectively inhibit HDACs within cutaneous lesions, but to be rapidly broken down in the bloodstream, preventing the side effects associated with systemically administered HDAC inhibitors.
- Medivir has acquired this clinical stage oncology program from TetraLogic Pharmaceuticals in December 2016.
Disease: early-stage cutaneous T-cell lymphoma (CTCL)
Therapeutic
area: Cancer - Oncology
Country: USA
Trial
details:
Latest
news:
- • On May 18, 2018, Medivir announced that additional data from the phase II study of remetinostat in patients with early stage cutaneous T-cell lymphoma (CTCL) have been presented during the International Investigative Dermatology (IID) meeting. The focus of the presentation is the effect of remetinostat on reducing pruritis (itching), as seen in the phase II study (Abstract).
- • On October 13, 2017, Medivir announced that phase II efficacy and safety data in patients with Mycosis Fungoides (MF) type early-stage Cutaneous T-cell Lymphoma (CTCL) demonstrated that remetinostat gel 1%, when applied topically twice daily, reduced the severity of CTCL skin lesions. Remetinostat also caused a clinically significant reduction in the severity of pruritus (itching) in those patients with clinically significant pruritus at the start of the study, and was highly tolerable with no systemic adverse effects.
- These data were contained in an abstract published at the European Organization for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Task Force meeting.
- The remetinostat phase II trial enrolled 60 patients with stage IA-IIA MF, the predominant variant of CTCL, across five different clinical sites in the USA. Patients were randomized to receive one of remetinostat gel 0.5% twice daily, remetinostat gel 1% once daily, or remetinostat gel 1% twice daily, for up to 12 months.
- The primary end-point of the study was the proportion of patients with either a complete or partial confirmed response to therapy, assessed using the Composite Assessment of Index Lesion Severity. The study showed a dose response with patients in the remetinostat gel 1% twice daily arm having the highest proportion of confirmed responses including 1 complete response. Based on an intent-to-treat analysis, confirmed response rates in patients were as follows:
| Dose Arm |
Number of Patients per Arm |
Number of Patients with Confirmed Response (whereof complete response) |
% of Patients with Confirmed Response |
| 1% twice daily |
20 |
8 (1) |
40% |
| 0.5% twice daily |
20 |
5 (0) |
25% |
| 1% once daily |
20 |
4 (0) |
20% |
As a secondary objective the effect of remetinostat gel on severity of pruritus was assessed monthly for the duration of the study using the visual analogue scale (VAS). Among patients with clinically significant pruritus at baseline, those who received remetinostat gel 1% twice daily had the highest proportion of patients achieving clinically significant reduction in pruritus from baseline. The proportions of patients who had confirmed, clinically significant, reductions in pruritus from baseline, defined as at least a 30mm reduction in the VAS score sustained for >4 weeks, were as follows:
| Dose Arm |
% Patients with Confirmed Clinically Significant Reduction in Pruritus from Baseline |
| 1% twice daily |
80% |
| 0.5% twice daily |
50% |
| 1% once daily |
37.5% |
Remetinostat was generally well tolerated, with adverse events evenly distributed across the treatment arms. The most common adverse events were skin related and mostly grade 1-2. There were no signs of systemic adverse effects related to remetinostat treatment, including those associated with systemic HDAC inhibitors. Most patients remained on study for the maximum possible duration and the median treatment time was 350 days. Based on the outcomes of the phase II study, Medivir expects to meet with regulatory authorities to discuss the design of a pivotal clinical program for remetinostat in MF-type CTCL.
- • On April 7, 2017, Medivir announced the completion of the phase II clinical study of the topical, skin-directed histone deacetylase (HDAC) inhibitor, remetinostat, in patients with early stage cutaneous T-cell lymphoma. The trial included 60 patients with the mycosis fungoides (MF) variant of CTCL, who were randomized to receive either 0.5% remetinostat gel BID, 1% remetinostat gel QD or 1% remetinostat gel BID for between 6 and 12 months.
- The primary end-point of the study was the proportion of patients with either a complete or partial confirmed response to therapy, assessed using the Composite Assessment of Index Lesion Severity (CAILS). Based on an intent-to-treat analysis, patients in the 1% remetinostat gel BID arm had highest proportion of confirmed responses (8/20, 40%), including 1 complete response. The response rates in the other two arms were 5/20 (25%) and 4/20 (20%) in the 0.5% BID arm and the 1% QD arm respectively, and did not include any complete responses. Across all the dose groups, remetinostat was well-tolerated without signs of systemic adverse effects, including those associated with systemic HDAC inhibitors.
Based on these data, Medivir expects to initiate discussions with regulatory authorities with the aim of initiating a phase III study later this year, and to present full phase II trial data at scientific meetings in the second half of 2017.
Is
general: Yes
