Why the huge costs and lengthy development times that exceed even those for conventional drugs? Regulatory excesses, for the most part. Regulators are inflexible and inconsistent and keep raising the bar for approval, especially for innovative, high-tech products.
Several highly publicized events have heightened public and congressional concern about drug safety during the past few years: inadequate warnings on the labels of antidepressants and the discovery of previously unknown adverse reactions to NSAIDs and the multiple sclerosis drug Tysabri.
However, contrary to perceptions that regulatory oversight might have become lax, drug regulation in the U.S. in recent years has actually become progressively more risk averse, as the FDA has steadily made it more difficult to initiate and perform clinical testing of new drugs.
Recent criticism from Congress, the media, and others regarding drug safety has caused an already risk-averse agency to become even more conservative and defensive in its decision making. The FDA has been requiring ever larger numbers of patients in clinical trials. Its demands for postmarketing clinical trials have proliferated wildly. Also, risk-management plans for newly approved drugs have been inconsistently applied, punitive, and often more appropriate for weapons-grade plutonium than prescription drugs.
Regulators moving the goalposts in the middle of the game is particularly vexing for drug developers. In September 2006, Genentech announced that approval of its colon cancer drug, Avastin, for breast cancer would be delayed at least one year because of requests from the FDA for additional data. The company said that regulators appeared to be increasing the stringency of requirements for certain types of clinical trials and had arbitrarily demanded that its trials be “audited and summarized” in a way different from that agreed upon earlier with regulators.
Another recent and particularly problematic example involves Somaxon Pharmaceuticals’ testing of an already-approved drug, doxepin, for a new indication. The drug, approved for the treatment of depression since 1969, is being tested in very low doses for use as a sleeping pill. FDA initially assured the company that it could begin clinical trials without first doing animal tests because of doxepin’s long history of use in people and because Somaxon was using a dose less than one-tenth of that used to treat depression.
In May 2006, however, after having completed several clinical trials, while the company was meeting with the FDA to discuss the submission of an NDA, regulators unexpectedly asked for a full battery of testing in animals.