4SC AG, a discovery and development company of targeted small molecule drugs for autoimmune diseases and cancer, announced that the US Food and Drug Administration (FDA) has granted orphan drug designation to 4SC's lead oncology compound resminostat for the treatment of hepatocellular cancer (HCC), the most common form of liver cancer. Resminostat is in phase II clinical development in advanced HCC, with results expected towards the end of 2011.

4SC is conducting its HCC SHELTER trial in a second therapy line setting in advanced HCC patients who prior to entry into this study are progressing under the only approved systemic first line therapeutic sorafenib. In this study resminostat is being explored in two study arms, i.e. in monotherapy and also in a resensitizing approach in combination with sorafenib.

Orphan drug designation is granted by the FDA to promote the development of products that may offer therapeutic benefits for diseases affecting less than 200,000 people in the USA. Orphan drug designations are based on several criteria that include frequency and seriousness of the condition, the lack of therapies and scientific merit of the proposed medicinal product and provide opportunities for significant fee and tax reductions before and after marketing authorization and the opportunity to obtain seven years of market exclusivity following drug approval, thereby offering competitive protection from similar drugs of the same class.

Even though HCC qualifies as an orphan drug indication in the USA, world-wide it represents the sixth most common cancer and the third leading cause of cancer-related deaths globally, rendering it a major health care problem. Most cases of HCC are secondary to either viral hepatitis infection or liver cirrhosis due to alcoholism. HCC has a particularly high prevalence in South-East Asia, as its cause is linked to high rates of hepatitis B virus infections present in this region. In North America and Europe, the incidence of HCC has historically been lower, however, also there the incidence of this cancer type is growing.

Ulrich Dauer, CEO of 4SC commented “Our strategy for the development of resminostat, an oral-HDAC inhibitor, has been to evaluate its mechanism of action in three cancer indications: hepatocellular carcinoma, Hodgkin's lymphoma and colorectal cancer. HCC presents a significant commercial market opportunity for resminostat as there are currently only very limited treatment options specifically for patients that suffer from advanced stages of this serious disease. We are excited about this FDA approval of our application for orphan drug designation which will support the development and potential future marketing of resminostat in this rare disease. We are looking forward to finalising results from the ongoing phase II SHELTER trial in 2011, from which we have so far announced encouraging interim data due to its open-label structure.”

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. It is currently being investigated in the phase II SHELTER study as a second-line treatment for advanced hepatocellular carcinoma and a phase II study, the SAPHIRE trial, in third-line treatment in Hodgkin's lymphoma. These two trials are expected to report phase II results in 2011. In addition, the phase I/II SHORE study is evaluating resminostat as a second-line therapy setting in colorectal cancer in KRAS-mutant patients.

Resminostat is currently partnered in Japan with Yakult Honsha.

4SC (ISIN DE0005753818) discovers and develops targeted small-molecule drugs for the treatment of diseases with a high unmet medical need in various autoimmune and cancer indications.