4SC AG, a discovery and development company of targeted small molecule drugs for autoimmune diseases and cancer, announced that the European Medicines Agency (EMA) has recommended 4SC's anti-cancer compound resminostat for designation as orphan medicinal product for the treatment of Hodgkin's Lymphoma (HL), a cancer of the lymphatic system. EMA's orphan medicinal product designation includes a ten-year period of market exclusivity from the date of approval in the European Union (EU) and allows direct access to a centralized marketing authorization and fee reductions.

Resminostat, 4SC's lead oncologic compound, already received in July 2011 a positive opinion for orphan medicinal product designation in the EU in the indication hepatocellular carcinoma (HCC), the most common type of liver cancer. Furthermore, resminostat recently obtained orphan drug status in the US for HCC and HL.

As recently reported, in the phase II SAPHIRE study as a third-line treatment in relapsed/refractory HL patients, resminostat showed a 33.3% overall response rate and a general clinical benefit in 54.5% of patients, demonstrating positive anti-tumour-efficacy and very good tolerability. Furthermore 4SC had published in June 2011 positive interim data from its phase II SHELTER study with resminostat in HCC patients. The oral pan HDAC inhibitor resminostat is, in addition to evaluation in HL and HCC, currently also being studied in a phase I/II trial in patients with colorectal cancer (CRC).

Dr Ulrich Dauer, CEO of 4SC commented: “We are delighted that the EMA has recommended our lead oncology compound resminostat for designation as orphan medicinal product also in HL. Based on the positive data from our phase II SAPHIRE study in HL and on the results of our phase II SHELTER study in HCC, which are anticipated by the end of this year, we plan to discuss the next development steps with regulatory authorities and potential partners. Consequently we expect the next step to be the planning of a pivotal development programme, especially considering the high medical need and the limited therapeutic options available in the indications addressed with resminostat.”

HL is a cancer of the lymphatic system, which is part of the immune system, and leads to the abnormal growth of lymphatic cells that compromise the immune system's ability to fight infection. The disease can spread beyond the lymphatic systems to other organs. The main causes for the development of HL are still unknown. Recent research shows that this tumour has its origin from a degenerated lymphatic cell, the B lymphocyte.

HL is curable in the majority of cases. However, not all patients can be cured and available therapies for this disease can have significant long-term toxicity. Therapy options for HL patients depend on the stage of the disease and number and regions of lymph nodes affected. The first treatment line for HL, after the initial diagnosis, consists of chemotherapy and/or radiation, achieving cure rates of up to 80 per cent. Standard of care for patients with refractory or relapsing disease after initial therapy consists of a salvage therapy comprising a conventional chemotherapy regimen usually followed by stem cell mobilization and subsequent high-dose chemotherapy along with autologous stem cell transplantation. Patients relapsing after second line therapy have a 5-year overall survival rate of only 17 per cent (Source: Sirohi et al., Ann.Oncol., 2008). Since there is no standard of care in patients with relapsed/refractory HL, there is an especially high need to develop novel therapies for these patients.

Resminostat (4SC-201) is an oral pan-histone-deacetylase (HDAC) inhibitor. HDAC inhibitors modify the DNA structure of tumour cells to cause their differentiation and programmed cell death (apoptosis) and are therefore considered to offer a mechanism of action that has the particular potential to halt tumour progression and induce tumour regression. Resminostat is currently being investigated in the phase II SHELTER study as a second-line treatment for advanced hepatocellular carcinoma and in the phase I/II SHORE study as a second-line treatment in colorectal cancer in KRAS-mutant patients. The SHELTER study is expected to report phase II results in 2011. Initial results of the SHORE study are expected in 2012. The reported phase II SAPHIRE trial for resminostat as a third-line therapy in Hodgkin's lymphoma is still ongoing as patients are continuing on study therapy in the optional follow-up phase beyond the study's main treatment cycle of 12 weeks. Resminostat is currently partnered in Japan with Yakult Honsha.