Three phase II studies with remetinostat have been conducted, one in MF-CTCL and two investigator-initiated studies in basal cell carcinoma and squamous cell carcinoma. Remetinostat has shown positive clinical efficacy and acceptable tolerability without systemic side effects in these three types of skin cancer.
MF cutaneous T-cell lymphoma (MF-CTCL) is a rare form of blood cancer that first shows up in the skin. MF-CTCL affects around 20,000 people in each of the US and Europe and approximately 75 percent of patients are in early stages (1).
In its early stages, the disease is confined to the skin and is not immediately life threatening. Patients do however experience a reduction in quality of life, and a key unmet medical need for patients in early-stages of MF-CTCL is efficacy on cancerous skin lesions and disease symptoms, mainly significant itching.
Patients also suffer an increased risk of infections as the protective skin barrier is no longer intact. Existing treatments do not sufficiently address the patient need. Thus, patients are in need of an efficacious but also highly tolerable treatment, since the early stages of disease may last for many years.
Medivir was developing remetinostat as a topical application for use in early stage MF-CTCL. Remetinostat is a histone deacetylase (HDAC) inhibitor. HDAC inhibitors are approved for treatment of MF-CTCL in late-stage patients but are not recommended for early-stage patients due to their significant side effects. The unique design of remetinostat enables topical application, making it active only in the skin. As soon as it reaches the blood stream, it is degraded, avoiding the side effects associated with other HDAC inhibitors.
In the phase II study, remetinostat demonstrated efficacy on skin lesions, reduction of itching and high tolerability in patients with early-stage MF-CTCL. This positive top-line data showed that patients that were given the highest dose in the study (remetinostat gel 1% twice daily) had the highest proportion of confirmed responses (40 percent, 8 patients out of 20). In addition, 80 percent of the patients in this dose group who had clinically significant itching at baseline experienced a meaningful reduction in the severity of their itching. Remetinostat was well-tolerated and without signs of systemic adverse effects in the study.
Remetinostat has been granted Orphan Drug Designation (ODD) in the US. In December 2018, Medivir had clarifying and positive discussions with FDA about the design of the phase III program for MF-CTCL. One successful phase III study is expected to be sufficient for market approval as treatment for patients with early-stage MF-CTCL. Medivir intends to seek a partner for the continued development and commercialization of remetinostat.
In a recently completed investigator-initiated study in collaboration with researchers at Stanford University, remetinostat was given to patients with basal cell carcinoma (BCC). The results indicated that remetinostat has potential as an effective and well-tolerated treatment of local skin tumors in BCC patients. In August, positive data from the phase II study in BCC was published in Clinical Cancer Research 2021 Sep 1;27(17):4717-4725, (online first doi: 10.1158/1078-0432.CCR-21-0560).
Results of the open-label clinical trial of the topical HDAC inhibitor, remetinostat, as neoadjuvant treatment for BCC were reported. Thirty-three per-protocol tumors from 25 participants were included in the analysis. The overall response rate (ORR), defined as the proportion of tumors achieving more than 30% decrease in the longest diameter from baseline to week 8, was 69.7% [90% confidence interval (CI), 54%–82.5%]. On pathologic examination, 54.8% of tumors demonstrated complete resolution. No systemic adverse events were reported.
At Stanford University, an investigator-initiated phase II clinical trial has been conducted in which remetinostat was given to patients with cutaneous squamous cell carcinoma (SCC). Further details of the study can be found at www.clinicaltrials.gov, reference number NCT03875859. The primary objective of the study was to assess the effects of topical remetinostat on biopsy-proven SCC and SCC in situ tumors. A publication of final data from the SCC study is now being prepared.