Discovered In Asia, Tested In The U.S.

It may not be long before the pill you take is a brand-name product from an Indian or Chinese drugmaker. At the end of August, China’s Hengrui gained U.S. Food & Drug Administration approval to begin testing a new drug to treat diabetes. Hengrui’s compound, retagliptin, will become the first small-molecule drug discovered in China to be tested on U.S. patients.

No drug invented and developed in India or China has yet gained FDA’s approval for market launch. But pharmaceutical R&D in China and India has come far in recent years, and numerous drug candidates from those countries are coming close to gaining the U.S. regulator’s nod.

A handful of Chinese firms are already conducting human clinical trials of their drug candidates in Australia and Canada. Further along than their Chinese counterparts, Indian companies have initiated clinical trials on a few dozen drug candidates in multiple countries.

Roughly 60 compounds from Indian companies are in various stages of human testing throughout the world, according to Swati A. Piramal, director of strategic alliances and communications at Piramal Healthcare, one of India’s leading pharmaceutical companies.

The number is not large. According to the trade group Pharmaceutical Research & Manufacturers of America, about 2,900 compounds are currently in clinical trials in the U.S. or are awaiting review by FDA. Most drug candidates fail to perform as expected during clinical trials, and FDA, after review of the clinical trial data, rarely approves more than 20 drugs for commercial launch in a single year. Nonetheless, Piramal expects that about six of the Indian molecules being tested will eventually be approved for U.S. market launch.

From 2012 onward, Piramal predicts, drugs developed in India will be regularly hitting the market. “They will be new-to-the-world drugs, unlike any other drugs seen before,” she says. Piramal Healthcare operates a modern drug discovery lab in Mumbai; it has four compounds in various stages of human trials in the U.S., Canada, India, and Europe. One compound in Phase II trials in the U.S. is for treating mantle cell lymphoma, a form of cancer that has so far been incurable. Phase II trials are conducted on 100 to 300 patients to determine the safety and effectiveness of a drug.

China’s drug discovery and development efforts have generally been hampered by a lack of experienced people, Greg B. Scott says. He is the founder and chief executive officer of ChinaBio, a Shanghai-based company that organizes conferences and provides intelligence on China’s biotech industry. There is not a shortage of scientists in China, he says, but rather a shortage of people with experience in managing the entire drug discovery and development process.

The chair of Hengrui, Piaoyang Sun, concurs. India is clearly ahead of China when it comes to drug research and development, he tells C&EN. “Indian firms started doing this earlier than Chinese ones,” he says. “They have a better understanding of regulations in the international drug market than we do; we’re lagging in that respect.”

Hengrui’s retagliptin is similar to Merck & Co.’s Januvia (sitagliptin), but the Chinese firm hopes it will prove more effective. Hengrui’s drug discovery strategy consists of patenting new compounds that improve on treatments already on the market. ChinaBio’s Scott nicknames such molecules “me-better” drugs.

Initially, Hengrui planned to develop new treatments for sale primarily in China, but the plan has changed slightly. According to Sun, Hengrui is still interested in China, but a global launch of its diabetes drug makes more sense. “We’ve come up with a drug that’s better than another drug already on the market, so we feel we need to go to the world market,” Sun says. At present, China represents at most 5% of the world’s drug market in terms of value, compared with about 47% for the U.S., he adds.

The team that developed retagliptin consisted of about 30 Chinese scientists, one-fourth of whom lived abroad for several years before returning to China, Sun points out. One of the main reasons Hengrui selected the U.S. for clinical trials, he says, is that most of the returnees at the company have U.S. drug R&D experience. “Our people with key knowledge of the global drug industry used to live in the U.S.,” he says.

In contrast, Jimmy Wei, head of business development at Shanghai-based Hutchison MediPharma, argues that speed should be the main reason for choosing a clinical trial locale. Hutchison has a plant-derived pharmaceutical treatment for ulcerative colitis and Crohn’s disease undergoing Phase II trials in the U.S. and four compounds about to begin Phase I trials in China and elsewhere.

The time to complete clinical trials, Wei says, depends partly on how long it takes for regulators to approve the trials and partly on how efficiently hospitals enroll patients. Beyond that, an important consideration is the commercialization strategy for the new drug. It makes sense to conduct clinical trials in a key country where a company plans to sell a drug, Wei says, because regulatory approval may be eased.

Before any compound from a Chinese or Indian firm can be commercialized in the U.S., it will have to complete the expensive Phase III clinical trials. These trials cost a lot more because they involve far more patients than do Phase I or II trials. Smaller companies typically cannot conduct Phase III trials on their own and usually seek a big drugmaker as a licensing partner after their compounds have successfully completed Phase II trials.

Some Indian firms, surprisingly, will conduct Phase III trials without the support of a larger partner, Piramal says. “Most of the Indian companies are midsized in the global context,” she says. “But we will conduct the Phase III trials for our cancer drugs on our own.” Phase III trials for cancer drugs, especially a relatively rare disease like mantle cell lymphoma, aren’t that costly because they do not require enrollment of a huge number of patients, she explains. For diabetes, however, “you need to enroll thousands of patients in Phase III, so we will need a partner,” she adds.

Among Chinese firms, Hengrui may be the only one so far that can afford conducting Phase III trials without a partner. As one of China’s largest generic drug manufacturers, Hengrui has sufficiently solid financial resources to underwrite the cost of testing a diabetes drug on thousands of patients, Sun maintains. A partner would have to bring something beyond mere capital to the table. “We might collaborate with others depending what they have to offer,” he says. More important, he adds, “we will first have to see how good our drug really is.”