Is the FDA raising the safety bar and approving fewer drugs to avoid a repeat of the Vioxx (rofecoxib) and Avandia (rosiglitazone) safety scares? Does the relative lack of approvals this year reflect the pharma sector’s failure to devise innovative new products? Or are both to blame?

Certainly, getting an innovative drug to market is tough. Take, for example, cancer, one of the most important areas of unmet clinical need. Research from the Tufts Center for the Study of Drug Development in Boston released in September found that “Although the number of new cancer drugs entering clinical development more than doubled between the early 1990s and mid-2000s, only eight percent of candidates with known fates won marketing approval in the United States”.

According to a report from DowJones posted on this week, the FDA approved 15 new molecular entities from the beginning of 2007 until October 31, excluding vaccines and new indications. “If that pace continues, the full-year tally would be about 18new drugs approved,” the report says. “The FDA still has two months to act on pending drug applications before the final tally for 2007 is known. But it might be tough to match the 22 new drugs approved in 2006 or the 20 approved in 2005.”

Nevertheless, some recently approved drugs are clinically important. Tasigna (nilotinib), approved last month for Philadelphia chromosome positive chronic myeloid leukaemia, offers a treatment for adults whose disease has progressed on or who cannot tolerate other therapies. Another drug approved in October, Ixempra (ixabepilone), treats metastatic or locally advanced breast cancer that has not responded to certain other cancer drugs, such as anthracycline and taxanes.

These examples illustrate that the FDA still seems willing to accept a degree of risk and act quickly if the benefits are sufficiently marked. The FDA issued a black box warning about potentially life-threatening cardiac toxicity with Tasigna and approved Ixempra in just six months.

Political pressure

Nevertheless, the Dow Jones report says that the FDA is under pressure from congress and consumer watchdogs to increase their vigilance about drug safety. This week’s report cites industry insiders who note, when there is an alternative drug on the market, the FDA makes increasing stringent demands. Also this week, the FDA issued a “not approvable letter” for GlaxoSmithKline’s antidepressant gepirone ER. The FDA also recently took a tougher line non-inferiority studies for demonstrating the effectiveness of antibacterial drugs.

According to the Dow Jones report the FDA says there have been no systematic changes approval standards for new drug applications and disputes that the pattern of approvals has changed since the early 1990s. As the report notes, the number of annual new-drug approvals varied from 17 in 2002 to 36 in 2004.

The new report also notes that some critics suggest that the sector’s poor record of innovation is to blame for the slow down. Dow Jones quotes Jerry Avorn, a professor at Harvard Medical School who studies drug evaluation, who says: "This continuing poor track record of innovation, even in the face of huge revenue inflows, seems to indicate that many of them [pharmaceutical companies] are far better at creative marketing than they are at creating useful new drugs."