Chinese pharmaceutical company Hutchison MediPharma Limited in Shanghai was chosen by the panel of judges for its product HMPL-004, an extract of the Chinese and Indian herb andrographis (Andrographis paniculata, Acanthaceae) that is intended to treat inflammatory bowel diseases. With more than 30 global patents and patent applications, HMPL-004 is the company’s key product. In 2005, Hutchison applied for an Investigational New Drug (IND) for HMPL-004 from the US Food and Drug Administration (FDA). In May of 2007, it completed a Phase II proof-of-concept study on HMPL-004 for ulcerative colitis and in 2009, completed Phase II clinical trials on HMPL-004 for Crohn’s Disease and ulcerative colitis.2
Andrographis and various extracts of the herb have been shown in several recent studies to exhibit antimicrobial, hepatoprotective (ability to protect the liver), antimalarial, antioxidant, and antidiarrheal properties.3 Several systematic reviews of controlled clinical trials on andrographis preparations (as well as andrographis combined with Eleutherococcus spp., Araliaceae) also have concluded that the herb is helpful in relieving symptoms of upper respiratory tract infections.4,5,6
While Hutchison declined to answer questions from the American Botanical Council (ABC), the company’s website says the product is “derived from a botanical extract;”7 is an “orally active, proprietary botanical product that acts on multiple targets in the pathogenesis of inflammation;” and is “a compound extracted from a Chinese herb under controlled conditions.”8 A Wall Street Journal story and a published scientific article identified the botanical as andrographis,9 and a 2007 Forbes Asia article as well as Hutchison's US patent application for the product report that HMPL-004 contains andrographolide.10
The results of the Phase II trial on HMPL-004 and ulcerative colitis were positive, with HMPL-004 showing similar efficacy to mesalamine, a drug commonly prescribed to treat ulcerative colitis inflammation and other symptoms. Study participants tolerated the product well, with some experiencing rash.11 According to Hutchison’s website, additional Phase II studies on HMPL-004 and ulcerative colitis and another on Crohn’s Disease were also successful,7 though these results have not yet been published in a peer reviewed scientific journal. Hutchison is reportedly planning to begin Phase III trials soon.9
“The significance of the research for inflammatory bowel disease is unknown at this time,” said Subhuti Dharmananda, PhD,* director of the Institute for Traditional Medicine and Preventative Health Care in Portland, Oregon (e-mail, August 14-21, 2011). “Initial results look promising, but there are also other herbs which have shown promise, such as wormwood (Artemisia absinthium, Asteraceae). Further testing will reveal how well this product works. If it does have a high rate of success, that could be quite significant, because the current [conventional pharmaceutical] drug regimens are far from ideal.”
Traditional and Modern Use
According to Dr. Dharmananda, medicinal use of andrographis (chuan xin lian) was first documented in China in 1936, and has been used in Traditional Chinese Medicine (TCM) mainly to treat infections, especially those of the respiratory tract, skin, and intestines, as well as viral hepatitis. The Pharmacopoeia of the People’s Republic of China documents the use of andrographis in dry herb and tablet forms for the treatment of influenza with fever, soar throat, ulcers in the mouth or on the tongue, acute and chronic cough, colitis, dysentery, urinary infection, carbuncles, sores, and venomous snakebites.12
Andrographis also has a history of traditional use in India. “There it has been used as a household remedy—alone or with other Indian herbs such as cumin [Cuminumcyminum, Apiaceae], anise [Pimpinellaanisum, Apiaceae], and cardamom [Elettariacardamomum, Zingiberaceae], or with cinnamon [Cinnamomumverum, Lauraceae], cloves [Syzygiumaromaticum, Myrtaceae], and cardamom—applied for many disorders, but especially for treating fevers and for intestinal disorders (cramping, diarrhea, etc.),” said Dr. Dharmananda. [Editor’s Note: Questions sent to the Indian Traditional Knowledge Digital Library (TKDL) regarding the legal status of Hutchison’s patents on this product were not answered as of press time. Since 2000, the TKDL has successfully challenged approximately 56 patents and patent applications on proprietary products using traditional Indian medicinal plants, e.g., neem (Azadirachta indica, Meliaceae)and turmeric (Curcuma longa, Zingiberaceae).]
A common usage of andrographis in China consists of decoctions (tea made by boiling the herbs) of 6 to 9 grams per day and up to 15 grams per day to treat infections, including some recipes that feature additional herbs to reinforce the intended effects of andrographis, said Dr. Dharmananda. But because andrographis has a bitter taste—sometimes inducing nausea—the herb is most often prepared as an extract in capsule and tablet form, Dr. Dharmananda continued. Extract products available in Asia contain from 30% to 50% of andrographolides, with a dosage of 200 to 400 mg of andrographolides per day used to treat upper respiratory tract infections and arthritis-related inflammation. Sometimes in Asia, according to Dr. Dharmanada, preparations of up to 98% andrographolides are used in dosages from 600 to 1,200 mg per day—an amount noted as “unbelievably high” by a peer reviewer of this article.
“Commercial products commonly sold in the West, containing as little as 10-40 mg of diterpene lactones per unit, may lead to significant under-dosing,” said Dr. Dharmananda.
Additionally, Dr. Dharmananda continued, using andrographis in its various forms is unlikely to produce the same effects as HMPL-004. “When a particular fraction is isolated from an herb, the pharmacology and clinical effects of that fraction may be entirely different than that of the whole herb,” he said. “This is especially the case when an herb has numerous different types of active constituents, as is the case with andrographis.”
The Wall Street Journal noted that Hutchison is one of several Chinese pharmaceutical companies that have long manufactured generic versions of Western drugs and are now developing new drugs.9 According to De-An Guo, PhD,* a professor at Shanghai Research Center for TCM Modernization and the Shanghai Institute of Materia Medica, Chinese pharmaceutical companies are growing very fast and now have enough capital to invest more in research and development. Also, the Chinese government provides financial support for many new product development programs. The reason why many companies are interested in botanicals used in TCM, Dr. Guo said, is very simple. “TCM has a long history of treatment of diseases in China and [shown] to be effective through clinical practice.”
Considering the scope of Chinese pharmaceutical innovation, some of the statements from Hutchison’s founder—as documented in the Wall Street Journal article—are not entirely accurate. Samantha Du, PhD, was quoted as saying that HMPL-004 is “the first major development of traditional Chinese medicine into a Western oral prescription pharmaceutical,” and “the first global herbal botanical oral product treating a serious disease.”
In fact, about 438 pre-IND/IND botanical product applications have been submitted to FDA as of 2009, said Dr. Guo. “There are about 10 Chinese Pharma [companies] filing applications and are now at different stages. [Hutchison] may be walking the fastest, but it is not the only one.”
As ABC reported in October of 2010, another is Tasly Pharmaceutical Company, Ltd., in Tianjin, China, which will soon begin Phase III clinical trials on its Danshen Dripping Pill.13 This product is meant to treat angina and coronary heart diseases, and contains extracts of Chinese salvia (Salvia miltiorrhiza, Lamiaceae; known as danshen), notoginseng (Panax notoginseng, Arialaceae), synthetic borneol, ginger (Zingiber officinale, Zingiberaceae), and other spices.
While noting that it can take up to 10 years from the start of Phase III trials to drug approval—and that many drugs still fail after Phase III—ABC reported that the Danshen pill “could become the first TCM product to obtain drug approval from the FDA.” And now, with both HMPL-004 and Danshen Dripping Pill seemingly at the same point in the journey to market, it is impossible to say which—if either—will be first.
* Members of the ABC Advisory Board
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