Once a week, Hashmukh Patel, a 62-year-old retired semiconductor engineer from Silicon Valley, travels with his wife, Bena, from their Beijing hotel to Beijing-Haidian Hospital. They ride the crowded elevator to the ninth floor, enter a pleasant, sun-filled ward with private rooms, and Patel gets an injection that he hopes will save his life. Suffering from late-stage cancer of the esophagus, he has come to Beijing for a Chinese gene-therapy drug called Gendicine that's supposed to kill tumor cells.
Patel tried just about everything before coming to China. He did three months of traditional chemotherapy, flew to the Bahamas for treatment at an alternative healing center, and tried to find clinical trials of experimental drugs. Nothing panned out. By late 2005, his doctors said that additional surgery or chemo could bring him only a few more months.
That wasn't good enough. "I'm not interested in buying time," says Patel, sitting on a couch at Haidian and holding his wife's hand. He had heard about Shenzhen SiBiono GeneTech Co., the producer of Gendicine, which in 2003 became the world's first commercially available gene-therapy drug. But the treatment, which is approved and available only in China, costs $20,000 per two-month course and isn't covered by U.S. health insurance.
SETBACKS IN THE U.S.
Patel is one of 70 foreign patients from 22 countries who have sought gene-therapy treatment at Haidian from Dr. Li Dinggang in the past year and a half. Li, the 50-year-old director of the Gene Therapy Center, is an oncologist who spent five years as a research fellow at Johns Hopkins University in the 1990s. Since 1997, he has worked closely with Dr. Peng Zhaohui, the chairman and chief executive of SiBiono, seeking to make China a leader in the field of gene therapy.
In the West, this experimental branch of biomedicine suffered major setbacks following the death of one patient in a clinical trial in 1999. Other patients later came down with cancer as a result of their added genes, and the U.S. Food & Drug Administration halted a number of trials.
That created an opportunity for Chinese researchers. Without the same regulatory obstacles, they were able to take ideas that originated in the U.S. but stagnated there. SiBiono's Gendicine, for instance, is similar to a gene therapy treatment that was pioneered by Introgen Therapeutics Inc. (INGN ) in Austin, Tex., but has yet to win approval from the FDA. As safety concerns forced the U.S. and Europe to apply the brakes, "China speeded up," Li says.
The Chinese are determined to keep the momentum going, and believe they can avoid the pitfalls that beset South Korea in stem cells. On Feb. 9, China's State Council announced a big boost in research and development spending to 2.5% of gross domestic product, from 1.3% now; biotech is a top priority. Li estimates that two dozen Chinese companies are developing gene-therapy drugs. "The Chinese are being very aggressive on this," says Dr. Jack A. Roth, chair of thoracic and cardiovascular surgery at the University of Texas M.D. Anderson Cancer Center in Houston. "They see a window of opportunity."
As a result, China has attracted not just American patients but also American researchers. James S. Norris, chair of microbiology and immunology at the Medical University of South Carolina, is president of the International Society for Cell & Gene Therapy of Cancer, which last December had a conference in Shenzhen, China. "If I were making a long-term investment in biotech, and particularly in gene therapy, I would be making it in China, not here," Norris says. "They have figured out how to get [gene therapy] approved." Norris is now trying to get funding to test his own promising gene therapy approach in China.
The father of gene therapy in China is SiBiono's Peng. Born in 1952 in the northern Chinese province of Shanxi, Peng has a joint PhD from a university in Xian and from Japan's Chiba University. Like Haidian's Li, he's a returnee from America, having worked at the medical school at the University of California at Los Angeles and at a biotech startup in San Diego in the mid-1990s. He launched SiBiono in 1998 with $300,000 in seed money from the Shenzhen government. Since then, SiBiono has received $5 million from private investors and more than $6 million in government grants.
Gendicine itself combines a gene named p53, which suppresses tumor formation, with a modified common virus. When the product is injected into a tumor, the virus carries the gene into cancer cells. The gene then prompts the tumor cells to commit suicide.
This basic approach was first developed by Introgen. The U.S. company's CEO and president, David G. Nance, believes that his patents cover SiBiono's treatment -- a view Peng disputes. Both companies have gotten similar results in clinical trials. Used with radiation or other treatments, the added gene causes more tumor shrinkage than the older treatments used alone. It remains to be proven that the treatment extends life, however, even though some patients have lived longer than expected. Another problem: While the gene can be directly injected into tumors that doctors can see, more clever delivery methods are needed to get it into metastasized cancer cells.
Despite questions about the technology's ownership and effectiveness, Peng has big plans for the privately held SiBiono. Construction is under way on a $20 million facility on the outskirts of Shenzhen that will be able to produce 1.5 million doses of Gendicine a year, compared with just 180,000 now. Peng says the company is talking with foreigners about potential partnerships. China is a logical place to work because more than 2 million Chinese get cancer every year. Clinical trials are inexpensive, at about one-tenth the cost in the U.S. And the regulatory climate is favorable. "The Chinese government is more open to innovation and new ideas, compared to the foreign counterparts such as the FDA in America," says Peng.
"WE ARE ALL ANXIOUS"
Some people wonder if Chinese regulators should have required longer trials before approving Gendicine. "Maybe they went into this prematurely," says Dr. Bauer E. Sumpio, chief of vascular surgery at Yale University School of Medicine. "It is hard to believe this would pass muster through our own FDA." Adds Takeo Ohnishi, a professor at Japan's Nara Medical University: "After the [problems] linked to gene therapy in the U.S, nobody wants to have anything to do with such treatments here."
Even in China, not everyone is sanguine. Cheng Jing, 42, is CEO of CapitalBio Corp., a state-backed biotech company in Beijing that is developing gene therapy. He fears that if Gendicine turns out to be ineffective, people will lose faith in all gene therapy. He says that he would feel more confident if there were test results from independent doctors treating patients in the years since the commercial launch. "We are all anxious," says Cheng.
Doctors close to SiBiono insist that China's first gene therapy drug is both safe and effective. Haidian's Li admits there are risks, but argues that's true for all other cancer treatments. "Surgery is risky," he says. "Chemotherapy is risky. Radiotherapy is risky." Gene therapy, he says, "can be used effectively to treat patients."
And thousands of patients, like Hashmukh Patel, are willing to take the chance. His decision to travel to China was not hard, he says. "I didn't think there was an alternative.'
By Bruce Einhorn, with John Carey in Washington and Kenji Hall in Tokyo