Drug Approvals Fall in 2010

Shortly after the US Food and Drug Administration (FDA) announced that the number of new drug approvals fell last year, a report indicated that the success rate of drugs going through clinical trials recently was lower than previously thought. The FDA approved 21 drugs in 2010, down from 26 in 2009 and 24 in 2008. Last year’s total included 15 new molecular entities and 6 biologics. Between late 2003 and the end of 2010, only 9% of drugs that entered phase 1 trials were approved by the FDA, according to an analysis released in February from the Biotechnology Industry Organization (BIO) and BioMedTracker, an institutional research service that examines clinical trial data. Drugs that were intended for lead indications had a 14.5% success rate compared with a 3.2% success rate for drugs intended for secondary indications. The authors said the study identified 4275 drugs and 7300 indications in any phase and included all privately and publicly owned pharmaceutical and biotechnology companies.

A previous study published in Clinical Pharmacology & Therapeutics [2010;87(3):272-277] examined the development histories of drugs from the 50 largest pharmaceutical companies (measured by sales) that entered clinical testing between 1993 and 2004. The authors found that the overall clinical approval success rate was 19%, which included licensed-in and licensed-out drugs and drugs originating from pharmaceutical companies. The approval rate for drugs originating from the pharmaceutical companies was 16% from 1993 through 1998 as well as from 1999 through 2004. The study only included drugs intended for lead indications. “We know that it’s not getting any easier to do drug development,” John Craighead, PhD, BIO’s managing director of investor relations and business development, said in an interview with First Report Managed Care. “Many people would argue the safety hurdles to get a drug approved are much higher than they used to be. In many cases, much of the low-hanging fruit in the industry is gone, so to be able to develop drugs has become more difficult, and it costs more money to develop drugs. “The bars for approval have increased, especially in the area of safety. In the risk:benefit ratio, there’s been a lot more focus on risk and a lot less focus on benefit. I certainly see that trend is unlikely to reverse itself in the near term without some changes in the regulatory process.”

According to a December 31 article in the Wall Street Journal, an FDA spokeswoman said there is “no systemic change in how the FDA is approaching drug approvals.” However, several drugs in 2010 had their approvals delayed for safety and other concerns. For instance, the FDA asked AstraZeneca for more information from a trial involving its application for Brilinta (ticagrelor), an oral antiplatelet treatment for acute coronary syndromes. The company provided the additional analyses in January, and the FDA set a new Prescription Drug User Fee Act date of July 20, 2011. The BIO study found that drugs making it to phase 2 trials had a 15% success rate of eventually getting approved, whereas those making it to phase 3 trials had a 44% success rate. Drugs that were submitted for approval after going through phase 3 trials had an 80% success rate. Drugs intended to treat cancer had the most difficult time getting approved once they reached phase 3, according to the researchers. Oncology drugs were approved 34% of the time compared with 46% for cardiovascular drugs, 55% for neurology drugs, 55% for infectious diseases drugs, 60% for endocrinology drugs, 61% for respiratory drugs, and 63% for autoimmune drugs. According to Dr. Craighead, oncology drugs are the least successful in gaining approval, likely because end points in earlier stage trials are not predictive of success in later stages.

In many cases, the FDA requires several large, outcomes-based studies in later stages that usually must include survival data, which are not found in earlier stages of development. The BIO study found a significant discrepancy in success rates in drugs intended for lead and secondary indications. Of the new molecular entities that entered phase 1 trials, 14% were successful for lead indications compared with 3% for secondary indications. Of the biologics that entered phase 1 trials, 26% were successful for lead indications compared with 7% for secondary indications. Dr. Craighead hypothesized that if compounds fail in a trial for a lead indication, pharmaceutical companies may stop development of the secondary indications. For instance, he explained that if a drug was found to lead to liver toxicity, all trials would be stopped. He also mentioned that companies might take more risks in secondary indications, which could lead to lower approval rates. Federal legislation may also play a role in coming years in regard to drug approvals. In February, President Barack Obama announced his budget proposal for 2012 that contained 2 provisions that could save $11 billion over 10 years, according to a Reuters article. The first would give drug makers a 7-year exclusivity period to market branded biologics compared with the current 12-year window. The second would provide the Federal Trade Commission with the power to block brand and generic companies from exchanging money to settle patent disputes, which is commonly referred to as “pay for delay.” By reducing the exclusivity window to 7 years, BIO said that biotech firms would have difficulty recouping their investment, according to the Reuters article.

The Pharmaceutical Research and Manufacturers of America released a statement to Reuters saying that the measures would decrease the amount that companies spend on research and development and may reduce innovation. “All companies are very concerned about the regulatory environment and the increasing costs and difficulty of getting a drug approved,” Dr. Craighead said. “We felt it was important to take a look at a larger and more recent data set of clinical success rates. “We support much more transparency in the regulatory process and other initiatives that help companies better communicate with the FDA to design better clinical studies. We need clear and direct, two-way communications between the agency and companies. We need clear, informative guidance about end points and what the barriers are to getting a drug approved in terms of safety and efficacy.”