Chinese medicine bowel drug ‘positive’
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Independent, Bloomberg, MediTech release – Hutchison China MediTech, an AIM-listed drug discovery group majority owned by Hutchison, the Hong Kong-based conglomerate and Asia’s largest company, is on the verge of making its first breakthrough after successful Phase II trials of HMPL-004, its ulcerative colitis and Crohn’s disease treatment.
Hutchison set up China MediTech as a first foray into the international pharmaceutical market and the positive trial data is derived from a compound found in traditional Chinese medicine, seen as a rich source of new drugs by many in the pharmaceutical industry. As a result of its long history of use among Chinese patients, the drug was able to bypass Phase I trials and move straight into FDA-approved Phase II.
What is 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. Ulcerative colitis generally affects the large intestine and Crohn’s disease generally affects the small intestine. Ulcerative colitis is the inflammation of the gut, which results in extensive ulceration of its inner surface with consequential pain, loss of function and blood loss. The disease can require surgical removal of sections of the gut and, in extreme cases, it may cause death.
Crohn’s disease displays similar but more severe laceration of the lining of the small intestine. Current first line treatments have effect on around 60% of patients. They can cause adverse events such as nausea, heartburn, diarrhea and headaches. Second line treatments can cause more severe adverse events and can be significantly more 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 to three times as many individuals may suffer from ulcerative colitis but are currently undiagnosed. Crohn’s disease is more prevalent with an estimated 558,000 cases in the US in 2005.
Current treatments include Aminosalicylates (5-ASAs) to reduce and control inflammation. In addition, corticosteroids and immunomodulators are prescribed for patients who do not respond to first line treatments.
The Phase II proof-of-concept study was a multicentre, randomized, double-blind, comparator study of 120 patients with mild-to-moderate ulcerative colitis conducted in China. The study evaluated HMPL-004 at 400mg taken three times a day, orally, compared to Mesalazine, the current first-line standard of care. The four trial endpoints were patients: clinical symptom score; overall clinical evaluation; colonoscopic score; and safety evaluation.
After treatment for eight weeks, the percentage of patient’s clinical symptom score reduction for HMPL-004 was 56% versus 59% for Mesalazine in the Intent-To-Treat population. The overall remission rate (combination of complete and partial remissions) for HMPL-004 was 57% by clinical score compared to 53% for Mesalazine in the Intent-To-Treat population and 47% for HMPL-004 versus 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 half that of the Mesalazine group.
How does HMPL-004 work? Extensive preclinical work with HMPL-004 has shown that HMPL-004 acts on multiple cellular targets in the inflammatory signal transduction pathways resulting in suppressed inflammation cytokine expression including TNF-alpha, IL-1beta and IL-6.
HMPL-004 was demonstrated to inhibit TNF-alpha and IL-1beta production in cell-based assays and is also able to inhibit NF-kB activation. The novel mechanism of action of HMPL-004, compared to current conventional therapies, including Mesalazine, allows it to access a unique patient population.
Moreover, Mesalazine is well known to be effective in about 60% of the patients it is used in and patients’ resistance over long-term use is common.
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 has extensive history of use in China and South East Asia against respiratory infections and inflammation.
The broker Investec believes that the successful commercialisation of the drug could result in it taking at least 20% of the global market by 2012 – a market that is currently worth a combined $3b per year, and that the drug could be worth an extra 80p per share for China MediTech. Shares in the company closed 2.5p better yesterday at 155p.
The US market for ulcerative colitis drugs was estimated to be US$420m in 2002 and is expected to reach US$500m by 2012, a CAGR of four percent. The US market for Crohn’s Disease drugs was estimated to be US$590m, growing to around US$980m by 2012. In both 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$1b by 2012 and, for Crohn’s Disease, the estimate is around US$2b.