Drug approvals are bogging down

Related articles

Patients and doctors cheered in 2008, when the Food and Drug Administration approved Genentech s Avastin for treating women with advanced breast cancer. Scientists had found that in many cases, the drug could prolong life, and today doctors prescribe it to some 17,500 women a year as their last, best hope.

In July, though, the FDA s advisory board recommended revoking Avastin s approval, which would be a nearly unprecedented step. A final decision will likely come Friday, but the agency usually follows the board s recommendations.

Unfortunately for cancer sufferers, this isn t the only case of the FDA standing between patients and cutting-edge treatments. In August, the agency rejected Immunogen s approval request for its drug T-DM1, which has also shown encouraging results against late-stage breast cancer unresponsive to multiple other treatments.

Because of their great promise in early trials, both Avastin and T-DM1 were eligible to be considered under the FDA s accelerated approval process. Normally the agency requires a series of smaller trials before approving a larger-scale Phase III study whose aim is to prove a clinical benefit. This accelerated process was inaugurated in 1992 to speed to market specialized medicines for deadly diseases such as AIDS and cancer for such important drugs, companies can ask for quicker decisions. If one is approved, the drug maker can then sell the medicine to a narrow group of patients in dire need, as long as it agrees to conduct follow-up studies. Without the faster approach, a promising drug can wend its way through the system for years.

Now, the FDA seems to be undermining its own accelerated approval policy. A trial of T-DM1 showed meaningful tumor shrinkage in a third of patients, while Avastin showed improvement in progression-free survival (PFS), a measure that counts patients who live for a period of time without deterioration. In the former case, the FDA claimed that patients had other options, and in the latter it cited studies that were less encouraging than initial results.

The FDA s excessive restraint in granting accelerated approval gives companies more reason to simply go forward with Phase III trials, and wait for regular approval. While the process takes longer, the drug will come to market with stronger scientific backing and reach more patients.

When it comes to drugs that show great promise, though, large, time-consuming, controlled trials seem cruel. Such studies randomly divide patients into an experimental group that gets the treatment under consideration and a control group that gets a placebo. This method has long been considered the gold standard for proving therapeutic benefit, because it allows researchers to compare the two groups.

The problem is that for patients with, say, metastatic breast cancer, or the deadly skin cancer known as melanoma, time is extremely short. Being assigned to the experimental group instead of the control group can mean the difference between life and death.

Whether drug companies seek early, difficult-to-get approval for a select few, or proceed with rigorous but lengthy final studies, patients wait and suffer. There s some hope if a drug is already approved for diseases besides one s own, since a doctor could prescribe it anyway, off-label. Avastin is used to treat lung, brain, kidney and colon cancers, and those approvals aren t under threat. But Medicare, Medicaid, and private insurers often refuse to cover off-label uses, which would leave patients facing prohibitive costs. An Avastin breast cancer treatment runs as much as $88,000 a year, a price tag that reflects the astronomical cost of research and development.

As pharmacogenomics and personalized treatments become commonplace, the pace of drug development is going to accelerate in coming years. But that means we re going to be confronted by more and more questions like those surrounding Avastin. The FDA has traditionally been highly risk-averse, preferring excess of precaution to being accused of laxity in its oversight. But the agency needs to recognize that when it comes to terminal diseases, its main focus should be expediting the approval process, so that patients can have the maximum number of options as soon as possible. As medicine races ahead, it would be a tragedy for bureaucracy to hold it back.

Dr. Gilbert Ross is the medical director of the American Council on Science and Health, a public health consumer-education consortium of scientists and physicians.