MF cutaneous T-cell lymphoma (CTCL) is a rare form of blood cancer that shows up first in the skin. A key unmet medical need for patients in early-stages of MF-CTCL is efficacy on cancerous skin lesions and the symptom of significant itching.
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 due to disfiguring 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.
In the US alone, 15,000 patients with early stage MF-CTCL represents a total market potential of USD 900 million.
Medivir is 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.
Early August 2018, the first patient with basal cell carcinoma (BCC) was treated with remetinostat gel in an investigator-initiated phase II study conducted by Stanford University School of Medicine in California. In May 2019 positive interim data from this study was presented at the 2019 Society for Investigative Dermatology (SID) annual meeting in Chicago, USA.
The patients enrolled had at least one BCC lesion of any subtype between 5 and 25 mm in size. The primary endpoint is overall response rate (ORR) and secondary endpoints include safety and tolerability. Interim results from the study:
Basal cell carcinoma could be another area of use for remetinostat.
In December 2019, the first patient was enrolled and is being dosed with remetinostat gel 1% in an investigator-initiated phase II clinical study in patients with squamous cell carcinoma (SCC). This clinical study is conducted at the Stanford University School of Medicine in California, USA under the leadership of the principal investigator, Dr Kavita Sarin. Medivir is providing remetinostat drug supply for this study, and has full access to, and the rights to use, all clinical data after the study is complete.
The primary objective of the study is to assess the effects of topical remetinostat on biopsy-proven SCC and SCC in situ tumors and could establish that remetinostat has the potential for use in other skin-associated cancers in addition to MF-CTCL.