To China For a U.S. Cancer Drug?

washingtonpost.com

07-05-07

BEIJING -- Every few days, Houston businessman Richard Weissenborn receives injections of a radical new cancer drug at a hospital here.

The treatment aims to check his head and neck cancers by replacing mutant genes with good copies. The treatment is still experimental in the United States, but in China, it was approved for marketing after a few years of testing.

The Chinese scientists behind the drug, Gendicine, see it as a milestone in the country's efforts to catch up with the West, proof that China can develop some of the world's most advanced medicine.

But a company in the United States says the Chinese drug is basically stolen property, rushed to market with inadequate testing and in violation of patent rights.

The dispute is the latest clash between the two countries in the broad field known as intellectual property. China in recent decades has prospered largely because of a talent for copying. The country duplicates goods others created but figures out how to make them more cheaply.

For years, that tactic focused on items like watches, purses and DVDs. But increasingly, China is moving up the value chain, copying such high-value goods and services as architectural techniques, cars and drugs.

The dispute over the gene-therapy drug is especially revealing in that scientific innovation is a pillar of American business. If other countries can learn to beat the United States to market with drugs and other technologically advanced goods, that could spell economic trouble in America.

According to Peng Zhaohui, founder of SiBiono GeneTech, which created the gene-therapy cancer drug and put it on the market in the breakneck span of seven years, the treatment is the latest accomplishment of Chinese genetic engineering, built on information publicly available in medical literature.

American scientists tell a different story.

David Nance, chief executive of Introgen Therapeutics of Austin, said SiBiono's drug is the same one that he and an American colleague developed 15 years ago. He said that while Introgen's drug was making its way past U.S. research hurdles, SiBiono stole the technology and rushed it to market, thereby infringing on Introgen's patents.

Introgen says it holds 258 worldwide patents, four of them in China. No lawsuit has been filed. Nance declined to comment about specific patents or to describe the company's Chinese patent position in detail, citing possible future litigation.

Peng, a former University of California at Los Angeles medical researcher, denies that his company is infringing on any patents held by Nance's company.

"In the West, there are still people who are suspicious about this first gene-therapy product and have doubts about its origins and clinical practices. But after 50 years of fighting cancer, humans haven't had any obvious advancement in treatment other than this," Peng said.

"It is absolutely untrue that our drugs are the same," Peng added. "There's a huge difference -- the only thing that is the same is the name" of the cancer-related gene the two companies target with their therapies.

Meanwhile, the drug is beginning to transform the way cancer patients are treated in China, offering an alternative to traditional treatments with harsh side effects, such as surgery and chemotherapy. As of last month, more than 5,000 patients had been treated with the drug.

Weissenborn, 64, has traveled to Beijing three times to receive the Chinese gene-therapy treatment. He's a believer in the drug and is angry it is not available in the United States.

"If I died today, I have already prolonged my life and have a quality of life that I could not have with any other cancer treatment," he said.

Outside China, gene therapy is considered a provocative and important theory, but efforts to develop treatments using it have been troubled.

Many diseases, cancer included, arise when genes develop mutations that warp their normal function. Perhaps half of all cancers include abnormal copies of a crucial gene known as p53, the body's "guardian gene." It plays a central role in detecting abnormal growth and ordering cells undergoing it to commit suicide. When p53 itself becomes disabled by mutations, though, cells can more easily turn cancerous.

Various approaches are being developed to exploit this knowledge to battle cancer. One is to use gene therapy to insert normal copies of the p53 gene into cancer cells.

But it has turned out to be difficult, in practice, to get functioning genes into cells from outside the body. Research in the United States slowed down temporarily in 1999 when a teenage patient at the University of Pennsylvania died in a poorly run gene-therapy trial and then again when three children in France were stricken with a leukemia-like condition after receiving experimental treatments.

Jack A. Roth, head of thoracic and cardiovascular surgery at the M.D. Anderson Cancer Center at the University of Texas at Houston, helped pioneer the technology that both Introgen and SiBiono use. He said the Food and Drug Administration has been reviewing this type of gene therapy for more than seven years.

"The approval process is a frustrating business. It's not only very slow but unpredictable," said Roth, who helped found Introgen.

Introgen's Nance said the company may apply for FDA approval to market a gene-therapy cancer treatment as early as the end of this year. Like Peng, he cautioned against too much optimism about the drug.

"We don't promise a cure," Nance said. "It's different in every patient -- some respond and get rid of their cancer, and some respond to a degree. Some patients just don't respond at all."

Even as Western researchers proceeded slowly because of problems in gene-therapy trials, SiBiono plowed ahead in China. The company's studies, most of them published only in Chinese medical literature, showed significant benefits, if not cures, from the p53 treatment. But skeptics said it was unclear whether initial results, such as tumor shrinkage, would lead to longer life for patients. Other researchers have said the initial trials had too few patients, fewer than 200.

Savio Woo, chairman of gene and cell medicine at the Mount Sinai School of Medicine in New York, has visited SiBiono's scientists in the southern city of Shenzhen. He said the company's work superficially "looks spic and span; on paper it looks fine." But Woo said he remains concerned because raw data for the trial had not been shared. "No one knows how clinical trials are done in China," he said. "Do they have quality control?"

Indeed, a broad scandal regarding food and drug safety has been unfolding in China in recent years, and the former head of China's drug-regulatory agency -- the same agency that approved Gendicine for marketing -- was sentenced to death recently for taking bribes.

By the time most patients arrive at the Beijing-Haidian Hospital Gene Therapy Center, the only one that accepts foreigners, they've exhausted other treatments.

Weissenborn had been told the only way to get rid of the cancer in his throat was radical surgery that would carve off part of his face. Arve Johnsen, 34, a fisherman from Oslo with brain cancer, was told he had a 3 percent chance of surviving the next five years. Deborah Weatherby-Falk, a nurse from Vancouver, had a recurrent tumor between her left eye and nose, a tricky place to operate.

Weatherby-Falk, an intensive-care nurse, read every medical journal article about the treatment she could get her hands on before she got on the plane.

"I understand the criticisms," Weatherby-Falk said. "I came despite them."

A handful of foreign patients, fewer than 100, get the injections shipped via courier to their homes. Most seek treatment from the Haidian clinic's director, Li Dinggang, a former Johns Hopkins University School of Medicine researcher. So far, more than 310 foreigners and 550 Chinese nationals have been treated with the gene-therapy drug here.

Li combines gene therapy with traditional treatments like surgery, chemotherapy and radiation along with Chinese herbal remedies. He estimates that about 70 percent of his patients obtain positive results but warns that no one knows why some patients benefit and others don't.

"I have to tell patients the truth," Li said. "Their cancer condition is very late. In this condition, they can come to China, but no one can guarantee anything."

Since the treatment is still considered experimental in most places, insurance won't cover it. Patients must wire a $10,000 cash deposit, to be applied against the $20,000 cost of a two-month course of treatment, before they set foot in the clinic.

Weissenborn first arrived last fall, when his cancer had spread from his tongue to his throat and lymph nodes. He had trouble swallowing and was losing weight. He considered suicide and alternative treatments from Mexico. "I would believe a witch doctor if he said he could help me at that time," Weissenborn said.

A broker that specializes in matching cancer patients with experimental treatments led him to Li's clinic. Doctors reading medical scans told him that after two courses of treatment, his cancer had disappeared.

He came back in March for a checkup, though, and the doctors told him his cancer had returned.

Researcher Richard Drezen in New York contributed to this report.