Pharmaceutical Industry Scrambles to Fast-Track Drugs

From Nature magazine

The experimental cancer drug ibrutinib has wowed in clinical trials, beating deadly blood cancers without the painful side effects of currently approved therapies. And it has raced through development and regulatory hurdles, in part thanks to a US program to accelerate the development of particularly promising drugs, says its developer Pharmacyclics, based in Sunnyvale, California.

The US Food and Drug Administration (FDA) launched the ‘breakthrough therapy’ designation in 2012, and the label has been eagerly embraced by the pharmaceutical industry. Recent months have seen a steady stream of drugs being submitted for review. For some firms — particularly young ones — the designation can bring an extra boost of cash by raising investor confidence.

But for all the fanfare, the industry is also watching closely to see exactly what benefits can be gained by having a drug reviewed through this route. “It’s like winning a beauty pageant,” says Timothy Coté, a former director of the FDA’s Office of Orphan Products Development who now runs a consultancy called Coté Orphan Consulting in Silver Spring, Maryland. “It doesn’t have specific tangible outcomes, but it does appear to have enlivened the community.”

The breakthrough therapy designation was created by the FDA Safety and Innovation Act, a law that requires the agency to fast-track promising drugs for serious or life-threatening conditions. The FDA aims to do this by meeting early and often with developers, as well as working with them to design clinical trials that deliver the needed data quickly and efficiently.

The industry leapt on the opportunity, so far submitting 99 applications for the designation. But the flurry of applications may partly be a product of confusion, says Coté: the FDA has avoided laying out detailed descriptions of what constitutes a breakthrough, and some companies are unsure of the criteria. “Most biotech chief executives with something in the clinic think that they’re already there,” Coté says — but 47 of the applications submitted in the past year have been denied. In most cases the denials are due to insufficient clinical data, the FDA says.

Although the lack of clear guidelines could be deemed confusing, the FDA’s avoidance of hard-and-fast criteria can actually be an advantage for some drugs, says Keith Flaherty, an oncologist at Massachusetts General Hospital in Boston. He was pleased, for example, to see the FDA bestow breakthrough status on a melanoma therapy called lambrolizumab. The drug, which is made by Merck (based in Whitehouse Station, New Jersey), is one of several in development that stimulate the immune system to fight cancer by blocking a protein called PD1. Lambrolizumab works in only about 38% of patients, which is well below the response rate for some other cancer drugs in development. However, doctors champion it because it has tolerable side effects and can yield unusually long-lasting responses. “Having it get that designation really put a spring in the step of many people in our community,” says Flaherty. “It showed us that the FDA really gets the importance of these drugs.”

There are lingering concerns that other aspects of the drug-development process might delay the ultimate impact of the breakthrough-designated compounds. Jeff Allen, executive director of the patient-advocacy group Friends of Cancer Research in Washington DC, notes that drugs are increasingly developed alongside medical tests that will select the patients who are most likely to benefit from them. The new law does not address the development of such tests, but unless their evaluation and approval is accelerated, a breakthrough drug — even if approved — may not achieve its full potential in the clinic, he says.

U.S. drug industry upset with Indian policies on patents

Category: Latest

Washington, September 30, 2013: 
The burgeoning Indian economy, which once appeared to be a potential key U.S. trade partner for decades to come, now has become a battleground over everything from brand-name drugs to big-budget Hollywood movies.

India’s handling of intellectual property rights and patents has raised the ire of lawmakers on Capitol Hill, governors from across the nation, business leaders and pharmaceutical giants — and if that path continues, analysts say, the economic relationship between the two nations may come to a grinding halt.

“A wide swath of U.S. businesses have been targeted by these [Indian] policies. It really seems to be a basic industrial policy of the Indian government right now to build up its own domestic industries, whether it be pharmaceuticals or the technology area or elsewhere. Hopefully, President Obama will be raising these issues and we can reach a solution here,” said Jay Taylor, vice president of international affairs at Pharmaceutical Research and Manufacturers of America (PhRMA).

India has revoked, or denied in one form or another, multiple U.S. drug patents, which lets Indian companies produce cheaper, generic versions for sale in the South Asian nation. While many of these brand-name drugs would be too expensive to sell in big numbers in a developing country such as India, pharmaceutical companies and U.S. officials say they never could have been developed without American investment and research.

The U.S.-Indian trade rift, bubbling for years, has reached the surface in recent months. It is expected to be a top topic when Mr. Obama meets with Indian Prime Minister Manmohan Singh on Friday in Washington.

This summer, more than 200 members of Congress wrote to Mr. Obama urging him to raise the issue “at the highest levels of the Indian government.”

This week, governors from 14 states — including Maryland Gov. Martin O'Malley, a Democrat, and Ohio Gov. John Kasich, a Republican — wrote a similar letter blasting India’s economic approach.

“Given India’s role as an economic leader among emerging countries, there is concern that India’s policies may have a spillover effect to other countries,” the governors said.

Those policies, analysts say, affect a wide range of sectors of the U.S. economy.

India has taken steps to allow only domestically manufactured products in the energy and technology sectors. The nation is one of the worst offenders when it comes to bootlegged copies of American films, analysts say, and has blocked imports of many other foreign products.

But the pharmaceutical industry perhaps has been hit the hardest.

More than a half-dozen drugs have had their patents revoked in favor of Indian production or have had “compulsory licenses” issued against them. Such licenses allow Indian companies to produce generic versions of the drug, even though it still is — or, in theory, should be — protected by patents.

In March 2012, the Indian government issued a compulsory license to a national firm to make cheaper versions of the drug Nexavar, co-produced and co-marketed by Onyx Pharmaceuticals Inc. of the U.S. and German giant Bayer Corp. The drug is used to treat kidney disease.

In April, an Indian court issued a ruling that denied a patent for the drug Glivec, used to treat leukemia and other illnesses. The product is manufactured and patented by U.S. firm Novartis AG.

According to PhRMA, the Indian court cited a rule requiring that the drug be proved to have “enhanced efficacy,” meaning it showed invention with health benefits not seen in previous drugs. Even though the drug is patented in 40 other countries, India has refused to patent it.