Health - New cystic fibrosis drug highlights approval dilemma

It is a landmark moment: 22 years after the cystic fibrosis gene was discovered, some patients are about to receive a drug called Kalydeco to treat the defect that causes their lungs to clog up with sticky mucus.

But will approving the drug pave the way for all manner of pharmaceuticals to treat rare genetic disorders? Before that can happen regulators may have to let patients take risks that many say they are happy to accept.

If the only obstacles were scientific, it would be all systems go. In recent years, fast and cheap DNA sequencing has transformed geneticists' ability to find mutations that cause disease. Methods for screening thousands of molecules for promising biological effects have also speeded up drug discovery. "We're at a point where we can take a disorder long considered intractable and change the course," says Ed McCabe, who heads the Linda Crnic Institute for Down Syndrome in Aurora, Colorado.

Fast screening – coupled with $75 million from the Cystic Fibrosis Foundation – allowed Vertex of Cambridge, Massachusetts, to develop Kalydeco and two other drugs being tested. Although Kalydeco has so far been approved only for 4 per cent of cystic fibrosis patients, who carry a specific mutation, the three drugs together could treat more than 90 per cent of people with the disease.

Before Kalydeco reached the market the US Food and Drug Administration had to accept that the limited numbers of patients meant it wasn't feasible to run "phase III" trials. Drugs are normally given to more than 1000 to test effectiveness and safety. Instead, the FDA allowed Vertex to run studies with just a few hundred, and accepted exhalation strength as a "surrogate" measure of effectiveness – rather than waiting to confirm that patients lived longer, with a better quality of life.

Emil Kakkis of the EveryLife Foundation for Rare Diseases in California says other drugs may not be able to take that route. The FDA tends to accept a surrogate measure if results from others with the disease show that it is an indicator of improvement. Such studies don't exist for rare diseases. EveryLife is backing the Ultra Act, being considered by the US House of Representatives, which would encourage the FDA to accept other evidence – from animal studies, for instance.

FDA spokeswoman Sandy Walsh says that the agency will apply "regulatory flexibility and scientific judgement" where there is strong evidence that a drug is effective and safe. But here's the rub: how to balance the consequences if anything were to go wrong against demands for a bolder approach from patients with no other options.

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