FDA Approves 30 Drugs in 2011

Despite pharmaceutical industry talk about stricter regulations and slower processes, the US Food and Drug Administration (FDA) approved 30 drugs in 2011, the highest total since 2004 and 9 more than in 2010. So far this year, the agency has already approved several more new products.

Still, it is unclear if the recent uptick in approvals is a trend or an aberration. There remains fervent discussion and sentiment for the FDA to improve its approval process and provide more transparency. The worry is that companies are not as willing to invest as much money on drug development without a clear understanding of how the system works.

The continuing weak economic conditions and the inherent riskiness involved in clinical trials have led to some major pharmaceutical companies scrutinizing their research and development (R&D) spending, making it difficult to predict if the FDA’s approvals will continue to increase.

Last February, Pfizer announced it would cut R&D by 30%, partly because top-selling drug Lipitor^® (atorvastatin) was set to lose its patent in a few months. Mikael Dolsten, MD, PhD, president of worldwide R&D at Pfizer, said there used to be a “disconnect” between R&D and financial considerations.

Now, rather than relying on big blockbuster products, Dr. Dolsten wants Pfizer to be a “sustainable engine for innovation” and always keep in mind its return on investment for research projects. Pfizer is placing more emphasis on aligning science, business, and financial interests when determining how it will spend its research funding.

“To me, that’s the right way to do it,” Dr. Dolsten said at the Biotechnology Industry Organization’s (BIO) CEO & Investor conference in New York in February.

Pfizer has created “biomedical hubs” in major regions where it can attract top researchers, according to Dr. Dolsten. For instance, its pain and sensory disorder practice is in the United Kingdom, cardiometabolic and neuromuscular initiatives are in Boston, biotechnology is in San Francisco, and oncology is in New York. Pfizer also has established innovation centers near top colleges in which academics and company researchers collaborate on developing drugs.

“I think that’s an intriguing way to look at the future,” Dr. Dolsten said.

As for emerging markets, Pfizer is taking a more cautious approach. Although there are potentially lucrative opportunities in some countries, Dr. Dolsten said Pfizer must maintain its quality control standards and ensure trials and drugs are safe and effective.

Moncef Slaoui, PhD, chairman of GlaxoSmithKline’s R&D, is also dealing with reduced budgets, but he does not consider the situation a negative in terms of drug development. For too long, Dr. Slaoui said, his R&D colleagues were “arrogant” and did not understand why companies would cut research spending. Last year, he noticed a change in attitude. People began realizing the huge budgets of years past will likely not return in the coming years and the amount of spending does not always correlate with successful drug approvals.

“Reality has set in,” Dr. Slaoui said.

Dr. Slaoui said pharmaceutical companies have a “major need for restructuring” and predicted that in the next 5 years, “the industry will look different, particularly in size.” He is currently “100% focused” on re-engineering R&D at GlaxoSmithKline, which no longer sets its R&D budget as a fixed percentage of sales. Two years ago, the company began publicly disclosing its rate of return on R&D spending. The rate increased from 11% to 12% last year, and Dr. Slaoui said he foresees a 14% return in the future. However, he would not reveal how GlaxoSmithKline calculates the rate.

James Greenwood, BIO’s president and chief executive officer and a former member of the US House of Representatives, moderated a panel at the BIO conference that included pharmaceutical executives as well as Stephen P. Spielberg, MD, PhD, the FDA’s deputy commissioner for medical products and tobacco.

Jonathan Leff, managing director of healthcare at private equity firm Warburg Pincus, said that in the past decade, the cost and time needed to develop a drug has increased significantly mainly due to FDA requirements concerning safety and the certainty that drugs are effective in treating patients.

“It takes too long and costs too much to develop drugs in many categories,” Mr. Leff said.

Still, according to data from the FDA’s Center for Drug Evaluation and Research, the number of drug applications has remained fairly consistent (between 34 and 39) in the past 5 years with the exception of 2010, when there were only 23 applications filed. Yet Dr. Spielberg acknowledged the process is sometimes long and difficult to understand because the industry is “going through a huge change in our understanding of biology.”

“This is an enormous change,” Dr. Spielberg said. “The complexity now is really overwhelming us.”

Dr. Spielberg explained that another reason for the FDA’s delay on making decisions is that the agency is sometimes overwhelmed with information that is either incomplete or conflicting.

“All processes in medicine are trade-offs,” he said. “You’ll never have all the data you need or want, but you have to act.”

Richard Pops, chairman and chief executive officer of Alkermes, mentioned that the industry also suffers from a poor reputation and said there is a “corrosive effect” on the public’s trust because the companies pay the FDA to approve its drugs.

Under the Prescription Drug User Fee Act (PDUFA), the FDA collects fees from drug manufacturers to aid in the approval process. The program began in 1992 to expedite approvals and has been renewed every 5 years. The current PDUFA expires in September, but it is expected to be renewed soon through 2017.

Mr. Pops, who testified in February in front of the House Energy and Commerce Subcommittee on Health during a PDUFA hearing, believes drug approvals should be science-based, transparent, and predictable.

Mr. Leff said the FDA should focus not only on a drug’s safety and efficacy, but also on innovative products. He called the FDA’s accelerated approval process a “terrific success.”

Accelerated approval began in 1992 for drugs that treat serious diseases such as cancer and fill an unmet need based on a surrogate end point. The FDA then requires postmarketing studies that confirm the product’s clinical benefit. Since 1996, there have been 68 cancer therapies approved under the accelerated system.

Still, the process has come under scrutiny. In February 2011, the FDA’s oncologic drugs advisory committee noted that more than half of accelerated approvals for oncology drugs were based on a single-arm study with no control group. The committee agreed that 2 randomized controlled trials should be the standard for approval and that single-arm trials should only be used for drugs intended to treat rare diseases and have a pronounced treatment effect.

The debate over the FDA’s timing and requirements in approving new drugs will continue for a long time, according to Dr. Spielberg. There is no perfect solution, he suggested, but it is important the agency and the pharmaceutical industry work together to find the best possible process.

“This is a team sport,” Dr. Spielberg said. “It requires collaboration. No one has a lock on wisdom.”