Faster FDA Spurs Breakthroughs As New Drug Approvals Surge

Life Sciences Law & Industry Report connects the dots among the many disciplines that make up the burgeoning life sciences industry, with biweekly updates on current regulatory, legislative,...

By Robert Langreth and Oliver Staley

March 24 — More new drugs are getting the green light in the U.S. as drugmakers take advantage of a speedier metabolism at the Food and Drug Administration.

Through March 19, the FDA has approved 10 new drugs, on pace to match last year’s total of 41, which was an 18-year high.

The agency is moving faster partly because of 2012 mandates from Congress, analysts and industry executives say. That is spreading investor and drugmaker optimism by boosting innovative drugs that promise the biggest benefit.

This year’s approvals include the first medicine in years for initial treatment of a common form of advanced breast cancer. On March 15, researchers published data showing two medications that could hit the market this summer may cut heart attacks and other cardiac events in half for patients with high cholesterol.

It’s “a boom period,” said Fred Hassan, a managing director at Warburg Pincus who ran two big drug companies. “Things are happening all over the place.”

While there are warning signs that the party is getting overheated, including payer resistance to annual price tags topping $100,000 for some drugs, full pipelines at many companies mean a strong approval rate through at least 2017, said Kurt Kessler, a Zurich-based consultant at ZS Associates.

Catalytic Conversion 

“It has been a cultural change at the FDA,” said Bernard Munos, a former Eli Lilly & Co. executive who founded InnoThink Center for Research in Biomedical Innovation, an Indianapolis consulting firm. “They see themselves as a catalyst for innovation.”

When a trial showed that Opdivo, a skin-cancer drug from Bristol-Myers Squibb Co., could extend survival in a hard-to-treat type of lung malignancy, the FDA’s top official for cancer drugs, Richard Pazdur, was alerted by statisticians on Dec. 19, weeks before company executives knew about the data. Impressed FDA reviewers started strategizing, resulting in approval for the lung-cancer use on March 4, more than three months ahead of the FDA’s deadline to act.

Of last year’s 41 new approvals, nine had the agency’s breakthrough designation for innovative drugs. Eighteen more benefited from other mechanisms for speedier reviews.

“We have applied an all-hands-on-deck mentality” when a treatment gains the breakthrough tag, said the FDA’s John Jenkins, director of the office of new drugs.

Renaissance Building 

Drug development for cancer and rare diseases have benefited from both the new FDA policies and advances in gene scanning that allow researchers to target drugs to patients most likely to benefit.

Much of the foundational research was sponsored by the government, which tripled funding of the National Institutes of Health to $30 billion in the 15 years through 2008, and has kept it at about that level since. The money provided “the building blocks to this renaissance,” according to Gregory Daniel, a fellow at the Brookings Institution.

Between 2010 and 2014, the FDA approved 37 cancer drugs, compared to just 19 between 2005 and 2009. This year it has approved four more.

Pfizer Inc.’s Ibrance was designated as a breakthrough by the FDA in April 2013, after a small trial showed the drug could slow the spread of advanced breast cancer. Over the next year, the company met nine times with the agency to discuss moving the drug forward, Pfizer said.

Speed’s Downside 

Approval came on Feb. 3—more than two months ahead of schedule—based on final data from the 165-patient trial showing that it stopped metastatic tumors from growing for 20 months, twice as long as standard treatment alone. In the past, approval could have taken years longer, because the FDA might have insisted on additional trials first, Pfizer R&D head Mikael Dolsten said.

One potential innovation threat is the concentration of cancer medicine in development, Kessler said. That could lead to too many drugs on the market offering only incremental benefits, payers refusing to cover them, and less investment in research and development, he said. More than 170 drugs will be approved in the next four years in the U.S., 30 percent of them for cancer, according to GlobalData, a London-based research firm.

Another danger: Drugs approved quickly based on sparse data may later be found to have side effects that cancel out their benefits, said Pierre Chirac, section editor for Prescrire, a nonprofit journal in Paris that reviews drug treatments.

New Incentives 

Some drugs being approved now “are so poorly assessed and have such a poor benefit-risk balance, it probably would be better if patients don’t take them,” he said.

Within the drug industry, laboratories have returned to the best scientific leads and abandoned a failed effort to reward scientists simply for the volume of new compounds they discovered, according to Mene Pangalos, who heads small-molecule drug discovery for AstraZeneca Plc.

The pressure for numbers caused “a disastrous collapse” in productivity, said Munos, the consultant. U.S. drug approvals, which peaked in 1996 at 53, dropped to just 17 by 2002. In trying to churn out a steady stream of products, scientists focused on the needs of marketers, not the most promising science, he said.

Dengue Breakthrough 

Now companies have created incentives for higher quality. At AstraZeneca, scientists are expected to publish research papers and are rewarded based on the quality of the journals and how influential their work becomes, Pangalos said.

Sanofi, the Paris-based drugmaker, changed the way it allocates spending to stimulate bolder thinking, according to Elias Zerhouni, head of R&D. Today, he said, 20 percent of the R&D budget goes toward “breakthrough innovation” for diseases with few treatments, 40 percent is aimed at new cures in established therapy areas, while the balance goes to extending the life of existing products.

One of Sanofi’s breakthroughs is the first vaccine for dengue, Zerhouni said. The vaccine, aimed at a mosquito-borne disease that kills about 20,000 people a year, could gain approval and reach the market this year in Asia, he said.

In cancer, drug companies are using genetic tests to identify patients that are most likely to benefit from their drugs in “a golden era of drug development,” said Patrick Mahaffy, chief executive of Clovis Oncology Inc.

Clovis is testing a treatment that works against lung tumors that have a mutation that makes them resistant to an older drug, Tarceva, from Roche Holding AG. Both Clovis’s drug and a rival product from AstraZeneca have FDA breakthrough status. The companies plan to apply for approval this year.

To contact the reporters on this story: Robert Langreth in New York at rlangreth@bloomberg.net; Oliver Staley in London at ostaley@bloomberg.net

To contact the editors responsible for this story: Gary Putka at gputka@bloomberg.net, Chitra Somayaji, Stephen West

 ©2015 Bloomberg L.P. All rights reserved. Used with permission.