Traditional medicine modernization – still a long, bumpy road ahead

July 4, 2007  
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Interfax – As drug discovery options run dry with fewer and fewer synthetic lead compounds and structure-based medicines being discovered, multinationals are increasingly turning to traditional Chinese medicines as a new source.

TCM modernization, the identification of an active ingredient in a herbal remedy that results in the mass production and marketing of a drug with a detailed pharmacokinetic profile, is the latest buzzword in the pharmaceutical industry, both home and abroad.

However, medical researchers have told Interfax that China’s TCM modernization is still in its early stages, and that a lack of standards and technology are inhibiting the modernization of TCMs.

Bottlenecks in TCM development

“There is no standard to assess the quality and efficacy of TCMs,” said Tang Senping, a senior researcher from the Shanghai Institute of Materia Medica. “So many researchers have to explore ways for the TCM sector to modernize.”

A lack of a set of standards for the industry is just one of the obstacles standing in the way to developing China’s TCM industry.

According to a TCM researcher, surnamed Bi, from the Institute of Materia Medica of the Chinese Academy of Medical Sciences, the more chemical analyses that are made on traditional Chinese medicine materials, the fewer the number of active ingredients are being discovered. “This in turn poses a technological challenge for TCM development,” Bi said.

It is also common that different TCMs will be used to treat patients with the same disease, and that when a TCM is used in a clinical trial, it often produces different clinical effects depending on the patient, Bi said.

Capital is also a key issue in TCM development. Some Chinese drug makers have developed TCM drugs with as little as 8 m yuan (US$1.05m), compromising safety and efficacy.

Artemisinin – China’s TCM success story

“China’s TCM modernization is still in its early stages,” Bi said. To date, only one Chinese-developed drug, artemisinin, has received international acclaim for its effectiveness in treating malaria symptoms.

Artemisinin, a substance extracted from the plant Artemisia annua L (sweet wormwood), has received approval from the World Health Organization for use in combination therapy to combat multi-drug-resistant Plasmodium falciparum, a widespread form of malaria that contributes to more than 500 million severe infections and more than 1 million deaths a year around the world.

Artemisinin has been used by Chinese people for centuries to treat fever but was further developed in 1972 by Chinese scientists as a remedy for malaria.

In response to increasing resistance to anti-malarials, the WHO recommends ACTs (artemisinin-based combination therapy) as the preferred alternative in areas experiencing resistance to conventional monotherapies.

There are now four ACTs available commercially. However only one, Coartem, a combination anti-malarial developed by Novartis AG, has received WHO pre-qualification, which means it meets standards that make it acceptable for procurement by United Nation agencies. The treatment, which was first registered in 1998, contains artemether, a derivative of artemisinin, as well as lumefantrine.

Currently Chinese pharmaceutical companies such as Kunming Pharmaceutical Group Ltd. supply Novartis with the raw materials for Coartem while Shanghai Fosun Pharmaceutical has teamed up with scientists from the Chinese Academy of Sciences to develop a new anticancer drug based on artemisinin.

TCMs to treat epidemics

AIDS, bird flu, SARS. You name the epidemic and more than likely, there is a TCM to treat it.

TCM experts convening at a seminar held by China’s Ministry of Health, the WHO and China Association of Chinese Medicine, agreed to formulate China’s own approach to the prevention and treatment of human avian influenza, by combining TCMs with modern medicine, according to Chinese media in January.

A similar treatment approach was developed in 2004 during the SARS epidemic. However, officially, the WHO does not recommend any herbal treatments for use in any disease.

In such cases, TCMs are being used as complementary medicines alongside western medicines to improve the immunity of patients.

“The big issues for herbal therapies in the eyes of Western patients and physicians are safety. Certification for purity and consistency of dosing is key. Another issue is drug-drug interaction [the effects of mixing one drug with another], a fact often overlooked when people buy medicines,” chief medical officer of World Link in China, Dr. Larry Perin, said.

China has long advocated the use of TCMs to treat AIDS and the MoH has subsidized or offered free treatment to poverty-stricken AIDS patients as a substitute for more expensive western drugs. However, while TCMs may be cheaper and enable broader treatment access to AIDS patients across China, scientific evidence and efficacy still remains a large, unanswered issue. Furthermore, drug interactions further increase the uncertainty of treatment with TCMs.

TCM development by multinationals

Some multinational companies are cooperating with Chinese research institutions on the development of plant medicines.

“The Institute of Materia Medica of the Chinese Academy of Medical Sciences has already cooperated with several foreign companies on the development of TCMs over the past two or three years,” Bi said.

Those co-operations include relationships with Taisho Pharmaceutical Co. Ltd., Bayer and Servia, which has lasted for more than 20 years. The institute received $8 million from Taisho to develop China’s first anti-hepatitis drug, bicyclol.

In November, 2004, the Shanghai Institute of Materia Medica and Novartis Pharma AG extended their cooperation on the research of plant medicines.

On the same day, phase one studies at Hutchinson Whampoa Ltd.’s TCM modernization research and production base was completed with an investment of 30m yuan (US$3.94m).

The Shanghai University of Traditional Chinese Medicines established its Ferid Murad TCM Modernization Center in 2003, to explore the relationships between nitric oxide and cardiovascular diseases, nervous system diseases, endocrine system diseases and inflammatory processes, and develop new strategies for the prevention and control of those diseases.

What will modernization do to China’s TCM industry?

TCM treatment is applied when the body’s forces, the yin and yang, are out of balance. There are other theories such as the five elements, Qi, Shen and the meridian system of the body, but the key concepts focus on the body attaining homeostasis and harmony through a holistic approach to maintaining good health.

Based on Taoist philosophy and more than 2000 years of experience, the main aspects of TCM treatment include acupuncture, moxibustion (application of heat on the body) and the use of Chinese herbal medicine.

Western medicine, on the other hand, is largely based on the symptom and cure method.

However, China’s TCM market already encompasses a whole spectrum of commercialized over-the-counter symptom-based cures readily available from the country’s 260,000 drugstores.

Many of these products are purchased without the advice of a TCM practitioner and more often, a pharmacist is not involved in the sale either. According to Zhang Shufang, the secretary-in-chief of the China Licensed Pharmacists Association, there are only 120,000 licensed pharmacists in China.

Already, this mass-marketing approach signals that perhaps, there could be loopholes in TCM theory.

Furthermore, China’s turn to “modernization” will be sure to rile some fundamentalist TCM scholars. The essential aim of modernization is to detect, formulate and apply the active ingredient of a TCM herb using western scientific approaches, otherwise known as evidence-based medicine.

Such a process will probably be no more different to that used in discoveries such as digoxin, an extremely potent medication for heart arrhythmia, and the tumor-killing cancer drug, paclitaxel, which are both derived from plants.

It seems that TCMs are already being backed into a corner. The Medicines and Healthcare Products Regulatory Agency of the United Kingdom announced in January it would seek public consultation over the review of a provision in the Medicine Act 1968, which will require a professional standard for TCMs, accountability of herbal practitioners, and plant medicines to meet European Union good manufacturing production (GMP) standards.

At present, very few Chinese TCM manufacturers hold EU GMP certificates while EU countries are the top destination of China’s TCM exports.

The TCM industry achieved sales of 114.01b yuan (US$14.73b) last year, recording profits of 10.42b yuan (US$1.35b). Profit growth for the year only reached 2.89% though, much lower than that of 2005, which was 8.85%.

However, if China’s maintains its push for TCMs as a complementary medicine, or continues its TCM modernization endeavors, the further building of standards such as GMP is necessary if Chinese manufacturers are to crack the international market and expand overseas.

One thing seems clear, all roads are leading in the one direction – towards the need for tighter standards.

Chinese medicine bowel drug ‘positive’

July 2, 2007  
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Independent, Bloomberg, MediTech releaseHutchison 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.

Take a break – YouTube acupuncture

July 1, 2007  
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A Netherlands insurance commercial involving a guy getting needles placed all over his body (a Chinese healing technique). Watch to find out what happens next!

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