February 29, 2008-Chi-Med today announces its wholly-owned drug R&D subsidiary, Hutchison MediPharma Limited (“Hutchison MediPharma”), has enrolled the first patient into its global Phase IIb trial programme assessing HMPL-004 in patients with mild-to-moderate Ulcerative Colitis (“UC”), a form of inflammatory bowel disease. This patient was screened and randomized per the study protocol at one of its clinical sites in the United States (“US”). The global clinical trial programme has been designed to further test the drug candidate’s efficacy, assess its safety profile in a broader patient population, and to evaluate different dose regimens in preparation for the Phase III trials with HMPL-004. The global Phase IIb UC trial will be conducted in approximately 50 clinical study centres worldwide including sites in North America and Europe. In July 2007, Chi-Med announced positive results from a Phase II proof-of-concept study conducted by Hutchison MediPharma with HMPL-004 in UC patients in China.
The global Phase IIb UC trial is a multi-center, randomized, double-blind, placebo-controlled clinical study, which will recruit 210 patients with active mild-to-moderate UC. The patients will be randomized into one of the two HMPL-004 treatment arms, 1200mg/daily or 1800mg/daily, or the placebo arm. The primary endpoint of the trial is to assess the efficacy of HMPL-004 as compared with the placebo after eight weeks treatment. In the trial the efficacy of HMPL-004 will be assessed based on quantitative symptom reduction thresholds using the standard Mayo score as well as a rectal bleeding score derived from colonoscopic examinations. Secondary endpoints of the trial involves the clinical remission, mucosal healing, and the dose response trend of the two HMPL-004 treatment arms. Safety evaluations will be made throughout the trial period. It is anticipated that patient recruitment in this global clinical trial will be completed by third quarter 2009.
HMPL-004, the leading candidate of Chi-Med’s drug pipeline for treating inflammatory bowel disease, is also being assessed as a potential treatment for Crohn’s Disease (“CD”). The product candidate is in a Phase II clinical trial in the US which is actively recruiting patients and Chi-Med anticipates the completion of patient recruitment for this CD study by the end of 2008.
Dr. Samantha Du, Chief Scientific Officer for Chi-Med and CEO of Hutchison MediPharma, commented on today’s announcement: “The start of the global Phase IIb trial with HMPL-004 in patients with Ulcerative Colitis is another milestone for Hutchison MediPharma. This study is designed to build on the positive Phase II results that we have generated in China and to provide us with the data we need to design our Phase III clinical trial programme. We believe, based on our clinical experience to-date and its unique mode of action, that HMPL-004 has the potential to become an important treatment of both Ulcerative Colitis and Crohn’s Disease.”
HMPL-004 is an orally active, proprietary botanical product that acts on multiple targets in the pathogenesis of inflammation. It is a compound extracted from a Chinese herb that is known for its extensive history of use in China and South East Asia against respiratory infections and inflammation. Chi-Med’s extensive preclinical work with HMPL-004 has shown that it acts on multiple cellular targets in the inflammatory signal transduction pathways resulting in suppressed inflammation cytokine expression including TNF-alpha, IL-1 beta and IL-6. In cell based assays, HMPL-004 has demonstrated its ability to inhibit TNF-alpha and IL-1 beta production and to inhibit NF-kB activation. The novel mechanism of action of HMPL-004, compared to current conventional therapies, including mesalazine, could allow it to be used in a broader patient population with inflammatory bowel disease.