What it’s used for: Tyrosinemia Type 1 (a rare genetic disorder that can cause liver failure in infants and young children)
Where it’s from: Red bottlebrush shrub
Sold by: Swedish Orphan International/Rare Disease Therapeutics
Can traditional Chinese medicine become a potent source of new drugs for the West? Asia’s richest man is betting on it.
by Kerry A. Dolan
Hold your nose if you take a tour of Shanghai Hutchison Pharmaceuticals’ factory on the industrial outskirts of China’s largest city. It’s where they make She Xiang Bao Xin, a pill made from synthetic deer musk, synthetic ox gallstones, an enemy-repelling toad secretion and four herbs. The odor hits you on the first floor, where masked workers shake the pills on enormous metal trays to separate the oversize ones. One floor up another large batch is brewing in a dozen 3-foot-tall metal vats. Adherents of traditional Chinese medicine cherish these pills for their heart-protecting powers. Shanghai Hutchison sold 200 million doses last year for $8.7 million, with sales up 17% from 2005.
Forty-five minutes away from the musk are the gleaming labs of Shanghai Hutchison Pharma’s sibling company, Hutchison MediPharma. This place is easier on the senses. A cadre of Chinese nationals with medical degrees and doctorates in biology and chemistry from North American universities and résumés that include Pfizer, Johnson & Johnson and Amgen, screen thousands of chemicals found inside Chinese herbs and plants on the latest high-speed machines. They’re looking for promising drug candidates to patent, like all the many labs in Shanghai’s pharma gulch. Roche is right across the street, Novartis and Eli Lilly down the block.
The two companies, Shanghai Hutchison and Hutchison MediPharma, straddle the old and new worlds of Chinese medicine, yet, amazingly, they share the same parent, Hutchison China MediTech, or Chi-Med. The Hong Kong company is going forward and backward at once. It aims to expand the market for traditional Chinese medicine while harvesting modern drugs from Asian flora. “It’s a massive objective we’ve set. We’re trying to modernize and globalize Chinese medicine,” says Chi-Med Chief Executive Christian Hogg, 42.
The name Hutchison can only mean one thing: the presence of Li Ka-shing, Asia’s richest man and chairman of the globe-girdling conglomerate Hutchison Whampoa, which has invested $72 million in Chi-Med since its inception in 2000. Chi-Med listed 28% of its outstanding shares on London’s AIM exchange last May; Hutchison owns the other 72%.
Chi-Med is a minnow compared with Hutchison Whampoa’s other concerns. The company lost $10 million last year on revenue of $58 million, up 52% over 2005, mostly from sales of the musk pill, a treatment for respiratory infection and an angina drug. But Li, 78, is so keen on the growth opportunity that he devotes some of his valuable time to signing off on Chi-Med joint ventures.
MediPharma has two drugs in mid-stage clinical trials in the U.S., one to augment radiation therapy on head and neck cancer and the other to treat Crohn’s disease, a chronic inflammation of the digestive tract. The active ingredient in the Crohn’s drug is a chemical found in an herb common in China called Indian echinacea or rice bitters. If approved, the drug would compete with J&J’s Remicade, which brought in $3 billion last year from treating Crohn’s and other diseases.
In November Procter & Gamble signed a two-year agreement with Chi-Med to screen traditional medicines for new ingredients for P&G beauty products. That same month Merck KGaA of Germany agreed to develop anticancer drugs with Chi-Med. The terms of these deals were not disclosed.
China’s approach to medicine is in transition. Many doctors trained in Western medicine scoff at traditional Chinese medicine’s lack of scientific grounding (even as they plumb its medicine cabinet for secrets). “We are not a folklore-based company,” says Samantha Du, the U.S.-trained biochemist in charge of Chi-Med’s drug development. The nation’s booming middle class readily embraces Western medicine but thinks nothing of adding a dash of ancient herbs to a meal. Chi-Med’s business development manager, Michael Leung, lives in Hong Kong with his wife, a private banker. “She takes bird-saliva nest and puts it in soup to help her skin look young,” he says.
Sales of Western pharmaceuticals in China grew 91% in five years to $13 billion in 2005, according to the Boston Consulting Group. That’s one-twentieth the size of the U.S. market but roughly equal, by some estimates, to the traditional Chinese medicine market. Some of this growth has been tainted by corruption. In 2005 Zheng Xiaoyu, the former head of China’s State Food & Drug Administration, was booted from office for taking bribes to obtain drug approvals, the Chinese media alleged. A fake version of one drug and improper production of another killed 21 people last year. Since last fall the agency has revoked 350 manufacturing licenses and vowed to tighten inspections, according to Chinese media.
A wave of herbal prospecting in China in the 1990s turned up little for several big firms such as Bayer, Eli Lilly and Pfizer. Novartis, however, scored a hit in 1998 with Coartem, an antimalarial drug that combines artemisinin, an extract from sweet wormwood, with a compound called lumefantrine. Sweet wormwood is used by Chinese herbalists to treat fever.
Last year MediGene of Germany got approval from the FDA for U.S. marketing of an ointment extracted from green tea leaves to treat genital warts. Sales in the U.S. are being handled by Bradley Pharmaceuticals. Cephalon sells a leukemia drug called Trisenox (arsenic trioxide). A similar active ingredient, arsenic stone, has long been used in China and elsewhere to treat fevers, depression and arthritis.
Chi-Med’s plant-finding took root in 1995, when Christian Hogg, an Englishman then at Procter & Gamble, was sent to introduce the Chinese to the company’s laundry detergents. While there, he got to know managers at Hutchison Whampoa, which owns 30% of P&G’s Chinese unit. In 1999 P&G transferred Hogg to Brussels, but he kept his passion for China.
Within six months he had hatched a business plan to bring Chinese medicine to the West, to be sold in fancy shops that would also offer acupuncture, massage and herbal treatments. Hutchison Managing Director Canning Fok liked that idea but also saw an opportunity to get in on sales of traditional Chinese medicine in China, a segment of the pharma business that had not yet opened to foreign investment. In 2000 Hutchison China MediTech was born. Hogg got enough money to go off and build the first few of what are now six Chinese herbal medicine shops in London, operating under the name Sen.
In 2000, when China finally opened the traditional medicine sector to foreign investment, Chi-Med was one of the first in. In 2001 it invested $35 million in joint ventures with two Chinese medicine companies, including the newly renamed Shanghai Hutchison Pharmaceuticals, and in 2005 put $17 million into a third firm.
Hogg wanted to set up an R&D arm but hadn’t the faintest idea how to run one. A recruiter found Samantha Du, a Chinese-born biochemist with a Ph.D. from the University of Cincinnati and eight years’ experience at Pfizer. Du, now 42, was being groomed for management at Pfizer but decided it might be better to run her own operation. She moved from Groton, Conn. to Hong Kong in 2001.
The next year Du set up a new research lab in Shanghai, which has a good supply of disciplined scientists and is cosmopolitan enough to lure back Chinese scientists from U.S. drug firms. Chi-Med promised her a $27 million startup budget. Du recruited from companies such as Amgen, Pfizer and J&J.
Plant-derived drugs, called botanicals, are devilishly hard to develop because herbs and flowers contain so many chemical entities that it’s hard to pinpoint their biological targets at a molecular level. Still, pharmacy shelves are chockablock with drugs that are either derived from plants (morphine, from poppies) or inspired by herbal remedies (aspirin, from an ancient willow-bark extract). The best-understood Chinese herbs have already been well covered, but in the past few years Du and her staff have screened 10,000 traditional Chinese medicines looking for ones that influence cancers and the immune system and have come up with a handful of new prospects.
In 2004 the FDA streamlined the development of botanical drugs by allowing drugmakers to skip early-stage safety trials if a drug candidate comes from an herbal remedy that is safe and legally marketed already. Chi-Med took its Crohn’s disease drug into midstage trials two years earlier than it would have otherwise. Results are expected later this year. Chi-Med’s second compound, which sensitizes head and neck cancer cells to radiation, is approved for use in China. U.S. trials are under way.
Funds to fuel Chi-Med’s research will come from the brisk sales of deer-musk pills and Hutchison Whampoa’s deep purse. In a few years China’s economy will develop enough to support lucrative Western-style drug reimbursements. Says Hogg: “We’ll see 10% to 20% growth for the next 10 to 20 years.”
Mouse Baldness Treatment – Hope For Humans
Scientists at the U. of Penn School of Medicine have found that hair 1) ___ in adult mice regenerate by re-awakening genes once active only in developing embryos. These findings provide unequivocal evidence that, like other animals such as newts and salamanders, mammals have the power to 2) ___. A better understanding of this process could lead to novel treatments for hair loss, other skin and hair disorders, and wounds. It was shown, that 3) ___ healing triggered an embryonic state in the skin which made it receptive to receiving instructions from wnt proteins, which are a network of proteins implicated in hair-follicle development. It was previously believed that adult mammal 4) ___ could not regenerate hair follicles, and that, mammals had no true regenerative qualities. However, researchers found that wound healing in a mouse model created an “embryonic window” of opportunity. Dormant 5) ___ molecular pathways were awakened, sending stem cells to the area of injury. Unexpectedly, the regenerated hair follicles originated from non-hair-follicle 6) ___ cells. Scientists, now, can influence wound healing with wnts or other 7) ___ that allow the skin to heal in a way that has less scarring and includes all the normal structures of the skin, rather than just a scar. By introducing more wnt proteins to the wound, the researchers found that they could take advantage of the embryonic 8) ___ to promote hair-follicle growth, thus making skin regenerate instead of just repair. Conversely by 9) ___ wnt proteins, they also found that they could stop the production of hair follicles in healed skin. In fact, increased wnt signaling 10) ___ the number of new hair follicles. This suggests that the embryonic window created by the wound-healing process can be used to manipulate hair-follicle regeneration, leading to novel ways to treat hair loss and hair overgrowth. (Source: Nature 17 May 2007).
ANSWERS: 1) follicles; 2) regenerate; 3) wound; 4) skin; 5) embryonic; 6) stem; 7) proteins; 8) genes; 9) blocking; 10) doubled