Metabasis liver cancer treatment granted EU orphan status

US-based biopharmaceutical company Metabasis Therapeutics has revealed that MB07133 has been granted orphan medicinal product status for the treatment of hepatocellular carcinoma (HCC), or primary liver cancer, by the EU Commission (EC).

The designation is based on a recommendation from the Committee for Orphan Medicinal Products (COMP) of the European Agency for the Evaluation of Medicinal Products (EMEA).

Primary liver cancer represents the fifth most common and third most deadly cancer worldwide and is reported to claim as many as one million lives a year. Around one million new cases of primary liver cancer occur worldwide each year. In Europe and the US, incidence of HCC has tripled in the last 15 years and is increasing at six to eight per cent annually. In 2006, there were 15,000-20,000 cases of HCC reported in the US and 35,000-40,000 in Europe.

MB07133 is a novel HepDirect prodrug of cytarabine monophosphate (araCMP) designed to produce the oncolytically active form, cytarabine triphosphate (araCTP), in the liver tumour, where it acts to inhibit cell proliferation through DNA damage to activate cell death.

Preliminary results from a phase I/II clinical trial for MB07133, which was completed in Q2 2007, were presented at the Annual Meeting of the American Association for Cancer Research (AACR) back in April 2007.

The first dose escalation trial showed that MB07133 was well tolerated at doses up to 2400 mg/m2/day when administered as a seven-day continuous IV infusion to patients with inoperable HCC. No clinically significant dose-limiting toxicities associated with the therapy and few treatment-related hepatic adverse events were observed.

The trial also revealed intra-hepatic tumour shrinkage and prolonged disease stabilisation in some patients. Intra-hepatic tumour reduction was observed in eight patients (29 per cent), and increased median overall survival was seen in these patients relative to the other patients in the study.

Dr Paul Laikind, Metabasis' CEO, said: "The granting of orphan medicinal product designation to MB07133 by the EC is an important piece of the global regulatory strategy for the development of this product candidate in the EU. The designation provides protocol assistance in which the EMEA will provide advice on the development of MB07133, which should improve the chance of success at the time of marketing authorisation to commercialise this much needed therapy."