Staving off CTCL: How a Potential New Maintenance Therapy Could Benefit Patients

Cutaneous T-cell lymphoma (CTCL) is a rare type of cancer where the T-cells that normally help stave off infections become abnormal and begin to affect the skin. Richard Staines reports on new trial findings that could improve quality of life and lengthen survival times for patients with advanced disease.

CTCL is a form of non-Hodgkin lymphoma, with distressing symptoms including itchy skin, tumours and lesions on the skin, enlarged lymph nodes and hair loss. Although it’s considered to be a slow-developing cancer it’s incurable and becomes life-threatening as the abnormal T-cells spread to other organs in the body such as the liver, lungs, or bone marrow.

Available therapies such as chemotherapy and monoclonal antibody therapy can put the disease in remission but unfortunately this lasts only a few months, and very few patients experience complete  responses. With the skin symptoms inevitably returning, doctors have been looking for ways to lengthen the period between treatment and remission.

Enter 4SC, a biotech from Planegg-Martinsreid, Germany, that is aiming to change this with Kinselby (resminostat), an oral histone deacetylase inhibitor (HDAC). 4SC is confident that patients will see significant benefits from resminostat which it says is the only proven maintenance therapy for CTCL.

It’s a drug class from which only a handful have been approved by the FDA, and it took until 2015 for an HDAC inhibitor to be approved as a cancer medicine in Europe, as part of a combination therapy for multiple myeloma.

A lack of efficacy in other diseases and side effects including gastrointestinal problems have held back their use but 4SC is hoping that the considerable benefits seen in the RESMAIN trial will outweigh any negatives as it prepares for a filing with regulators, first in Europe, Japan and then with the U.S. FDA.

A phase 2 pivotal trial, RESMAIN, compared resminostat with placebo in patients with advanced stage mycosis fungoides and Sezary Syndrome, the two forms of CTCL.

Prof Rudolf Stadler, of University Center Minden, said in a webcast outlining the results, that RESMAIN began in 2016 and was designed as an innovative study of resminostat as a maintenance therapy in CTCL.

Prof Julia Scarisbrick, from the University of Birmingham, said: “This is the first time we have seen an effective maintenance therapy for CTCL.  It is a great opportunity for our patients and clinicians will be very happy to have a new option to delay disease progression”.

RESMAIN has reported findings, which showed a statistically significant improvement in progression free survival of (median) 8.3 months in patients treated with resminostat, compared with 4.2 months in the placebo group.

It also significantly improved the time to next treatment vs placebo (median 8.8 months vs 4.2 months) and a clinically meaningful improvement in total PFDA vs placebo (24.2 months vs 14.9 months).

Those on treatment were prescribed three 200mg capsules a day, on day 1 to 5, every two weeks. There was no significant effect of resminostat on VAS itching or Skindex, although the quality-of-life measure (Functional Assessment of Cancer Therapy – General) was affected by gastrointestinal side effects of resminostat, predominantly nausea.

Addressing the issue of the management of side effects, the company pointed out that the dosing regimen where patients only receive therapy for the first five days in a two-week cycle is designed to make the course as tolerable as possible. Prof. Scarisbrick added that the side effects were “mainly mild to moderate, manageable and reversible, and that real-life patients can opt to take treatment holidays, or use anti-emetic drugs if side-effects become difficult to manage”.

CEO Jason Loveridge commented that work on a filing with the European Medicines Agency was well underway and is due for submission in the first quarter of 2024. This will be followed by a filing in Japan by partner and licensee Yakult Honsha, as well as filings in the UK and Switzerland by 4SC. The company also intends to initiate talks with the FDA in 2023 regarding registration requirements in the US and 4SC has begun work on pricing strategies for the EU.

While it’s too early to give details, Dr. Loveridge pointed out that the drug has been granted orphan drug designation in both the U.S. and Europe which gives a series of significant benefits to developers including market exclusivity should the regulatory reviews go to plan: “It’s an orphan indication but a very significant one from a commercial point of view with around a $600 million market potential over the first 10 years on the market,” he said.

Richard Staines, account director at Optimum Strategic Communications, made a move into PR with Optimum after more than twenty years as a journalist. He was most recently a staff writer for BioWorld, following jobs as news editor for pharmaphorum and as senior reporter for the industry newsletter APM Health Europe. With experience writing for websites, national newspapers, and magazines, Staines has always had a keen interest in health and has been writing about pharma and biotech since 2010.