Hutchmed Regulatory News (HCM)

2 Jul 2007 07:01

Hutchison China Meditech Limited02 July 2007 Hutchison China MediTech Limited ("Chi-Med") (AIM: HCM) Chi-Med Announces Positive Phase II Proof-of-Concept Data for HMPL-004 in Ulcerative Colitis London, Monday, 2 July 2007: Chi-Med, the Hutchison Whampoa backedpharmaceutical and healthcare Group, today announces positive results for itsPhase II proof-of-concept study for HMPL-004 in mild-to-moderate UlcerativeColitis, a form of inflammatory bowel disease. The trial met its objective inthat HMPL-004 was well tolerated and showed an equivalent drop in clinicalsymptom score to the comparator drug, Mesalazine, the current first-linestandard of care in mild-to-moderate Ulcerative Colitis. The Phase II proof-of-concept study, conducted by Chi-Med's wholly-owned drug R&D subsidiary, Hutchison MediPharma Limited ("Hutchison MediPharma"), was amulti-center, randomized, double-blind, comparator study of 120 patients withmild-to-moderate Ulcerative Colitis conducted in China. The study evaluatedHMPL-004 at 400mg taken three times a day, orally, compared to Mesalazine, thecurrent first-line standard of care. The four trial endpoints were patients:clinical symptom score; overall clinical evaluation; colonoscopic score; andsafety evaluation. After treatment for eight weeks, the percentage of patient'sclinical symptom score reduction for HMPL-004 was 56% versus 59% for Mesalazinein the Intent-To-Treat population. The overall remission rate (combination ofcomplete and partial remissions) for HMPL-004 was 57% by clinical score comparedto 53% for Mesalazine in the Intent-To-Treat population and 47% for HMPL-004versus 42% for Mesalazine by colonoscopy in the Intent-To-Treat population.HMPL-004 was well tolerated in the study and the adverse event rate was halfthat of the Mesalazine group. Chi-Med's extensive preclinical work with HMPL-004 has shown that HMPL-004 actson multiple cellular targets in the inflammatory signal transduction pathwaysresulting in suppressed inflammation cytokine expression including TNF-alpha,IL-1beta and IL-6. HMPL-004 was demonstrated to inhibit TNF-alpha and IL-1betaproduction in cell-based assays and is also able to inhibit NF-kB activation.The novel mechanism of action of HMPL-004, compared to current conventionaltherapies, including Mesalazine, allows it to access a unique patientpopulation. Moreover, Mesalazine is well known to be effective in about 60% ofthe patients it is used in and patients' resistance over long-term use iscommon. The Directors believe that today's result is highly important because itshows that HMPL-004 has a similar margin of effect yet offers a differentmechanism of action and therefore provides a direct alternative to the currentbest standard of care. If ultimately approved, HMPL-004 will provide significantcommercial value to Chi-Med. HMPL-004 is an orally active, proprietary botanical product that acts onmultiple targets in the pathogenesis of inflammation. It is a compound extractedfrom a Chinese herb that has extensive history of use in China and South EastAsia against respiratory infections and inflammation. This documentation enabledChi-Med to accelerate the clinical process for HMPL-004 by by-passing Phase Itrials, based on the FDA's 2004 guidance on botanical drug products. HMPL-004 iscurrently also in Phase II trial in the US for the treatment of Crohn's Disease. Chi-Med has a further botanical candidate, HMPL-002, a radio-sensitizer for headand neck and non-small cell lung cancer, which is in Phase I/II in the US and inproof-of-concept study in China. Chi-Med's further pre-clinical drug developmentpipeline is focused on oncology and auto-immune indications. These compoundsinclude synthetic and semi-synthetic single chemical entities in addition tobotanical and natural product candidates. At the meeting of Hutchison MediPharma's Scientific Advisory Board held inShanghai, China in late-June 2007, the Board, which includes key opinion leadersin the inflammatory bowel disease area, such as Dr. William J. Sandborn,Professor of Medicine at the Mayo Clinic College of Medicine, Vice Chair of theDivision of Gastroenterology and Hepatology, and Director of the InflammatoryBowel Disease Interest Group of the Mayo Clinic and Dr. Stephan Targan, Directorof both the Inflammatory Bowel Disease Center and Division of Gastroenterologyat Cedars-Sinai Medical Center, Los Angeles expressed high enthusiasm overHMPL-004. Dr. Stephan Targan commented: "HMPL-004 has a different mechanism of action. Based on the promising resultsfrom this study, HMPL-004 is warranted for further clinical studies to fullyevaluate its efficacy and safety profile for the treatment of UlcerativeColitis." Dr. Samantha Du, Chief Scientific Officer of Chi-Med and Managing Director ofHutchison MediPharma said: "This is a significant milestone for us. We are encouraged by the positiveresults from this study, which suggest HMPL-004 can be a novel class ofanti-inflammatory drug for the treatment of Ulcerative Colitis. We believe thatHMPL-004 has significant potential to bring patients another option for thetreatment of this chronic, painful and frequently recurring disease, which maylead to abdominal surgery. We are looking forward to further clinical studies tofully evaluate the clinical benefits of HMPL-004. Today's announcement furthervalidates our new drug discovery and development capability and will alsofurther accelerate recruitment in the on-going Phase II Crohn's Disease trial inthe US." Mr. Christian Hogg, CEO of Chi-Med, said: "We are extremely pleased with the trial results, which fully meet ourexpectations. Ulcerative Colitis and Crohn's Disease are core focus areas of ourR&D programme, and we also look forward to the delivery of the Phase II resultsfor HMPL-004 in Crohn's Disease after which we would seek to out-license thisproduct, in line with our stated strategy. Today's results once more alsohighlight the potential of Traditional Chinese Medicine to provide a reservoirfor innovative new drugs for the global pharmaceutical market." Ends Enquiries Chi-Med Telephone: +852 2121 8200Christian Hogg, CEO Citigate Dewe Rogerson Telephone: +44 (0) 20 7638 9571Anthony Carlisle +44 (0) 7973 611 888Yvonne Alexander +44 (0) 7866 610 682 Notes to Editor About Intestinal Bowel Disease Ulcerative Colitis and Crohn's Disease are forms of inflammatory bowel disease,which is considered an auto-immune disorder. They are chronic diseases which,once they start, recur regularly and cannot currently be cured. UlcerativeColitis generally affects the large intestine and Crohn's Disease generallyaffects the small intestine. Ulcerative Colitis is the inflammation of the gut,which results in extensive ulceration of its inner surface with consequentialpain, loss of function and blood loss. The disease can require surgical removalof sections of the gut and, in extreme cases, it may cause death. Crohn'sDisease displays similar but more severe laceration of the lining of the smallintestine. Current first line treatments have effect on around 60% of patients. They cancause adverse events such as nausea, heartburn, diarrhea and headaches. Secondline treatments can cause more severe adverse events and can be significantlymore expensive. In 2005 in the US, Ulcerative Colitis affected approximately 347,000 patients,an increase from around 300,000 patients in 2001. Potentially a further two tothree times as many individuals may suffer from Ulcerative Colitis but arecurrently undiagnosed. Crohn's Disease is more prevalent with an estimated558,000 cases in the US in 2005. The US market for Ulcerative Colitis drugs wasestimated to be US$420 million in 2002 and is expected to reach US$500 millionby 2012, a CAGR of four percent. The US market for Crohn's Disease drugs wasestimated to be US$590 million, growing to around US$980 million by 2012. Inboth cases, the global market is estimated to be twice the size of the US.Global sales of Ulcerative Colitis drugs are estimated to reach US$1 billion by2012 and, for Crohn's Disease, the estimate is around US$2 billion. Currenttreatments include Aminosalicylates (5-ASAs) to reduce and control inflammation.In addition, Corticosteroids and Immunomodulators are prescribed for patientswho do not respond to first line treatments. About HMPL-004 HMPL-004 acts on multiple cellular targets in the inflammatory signaltransduction pathways resulting in suppressed inflammation cytokine expressionincluding TNF-alpha, IL-1beta and IL-6. HMPL-004 was demonstrated to inhibitTNF-alpha and IL-1beta production in cell-based assays. HMPL-004 is also able toinhibit NF-kB activation. NF-kB is a family of transcriptional factors thatregulate a wide spectrum of genes critically involved in host defence andinflammation. The mechanism of action of HMPL-004 was further supported ininflammatory bowel disease pre-clinical models. Treatment of inflammatory boweldisease rats with HMPL-004 caused a significant drop in plasma cytokineconcentrations, including TNF-alpha and IL-1beta. Pre-clinical trails forHMPL-004 have shown the almost total restoration of the inner lining of the gut. About Chi-Med Chi-Med is the holding company of a pharmaceutical and healthcare group basedprimarily in China and was admitted to trading on the Alternative InvestmentMarket of the London Stock Exchange in May 2006. Chi-Med is focused onresearching, developing, manufacturing, and selling pharmaceuticals, healthsupplements and other consumer health and personal care products derived fromTraditional Chinese Medicine and botanical ingredients. Hutchison MediPharma is Chi-Med's wholly-owned drug R&D subsidiary and has ateam of around 120 scientists and staff focusing on botanical drugs,semi-synthetic natural product drugs, and synthetic single chemical entitydrugs. It currently has two candidates in clinical development in both the USand China. HMPL-002, a radiosensitiser for head and neck and non-small cell lungcancer, is in Phase I/II in the US and in proof-of-concept in China. HMPL-004,an inhibitor to a group of inflammatory cytokines, has completed a Phase IIproof-of-concept study in Ulcerative Colitis and is in Phase II studies inCrohn's Disease in the US. Hutchison MediPharma also has a pipeline of singlemolecular entity discovery projects in auto-immune/inflammatory diseases andoncology therapeutic areas, which have shown activity against clinicallyvalidated targets. Chi-Med is majority owned by Hutchison Whampoa Limited, an internationalcorporation listed on the Main Board of The Stock Exchange of Hong Kong Limited. This announcement does not constitute or form part of any offer of securities,or constitute a solicitation of any offer to purchase or subscribe forsecurities. This information is provided by RNS The company news service from the London Stock Exchange