By David Pittman, Washington Correspondent, MedPage Today
Published: May 22, 2013
WASHINGTON -- The FDA will need to "turn the clinical trial paradigm on its head" in order to allow more specifically targeted, personalized drug therapies to get on the market faster, a top agency official said Tuesday.
"We are going to have to change the way drugs are developed. Period," said Janet Woodcock, MD, head of the FDA's Center for Drug Evaluation and Research.
Answering every question needed from regulators about targeted therapies -- such as who should receive the drug, at what dose, and with what expected side effects -- won't be possible in a traditional clinical trial, she explained at a luncheon hosted by the Personalized Medicine Coalition, a group of insurers, drugmakers and patient communities here whose goal is to "promote the understanding and adoption of personalized medicine concepts, services and products to benefit patients and the health system," according to its website.
Instead of embarking on traditional clinical trials, drugmakers and clinical investigators need to work in different ways to select patients for what will inevitably be smaller trials, she said.
"Ever smaller subsets of patients are being identified, and we're really going to have to put our heads together and figure out how do you study these small subsets of diseases," Woodcock said in a 45-minute speech on the FDA's efforts to advance the field. "What types of trials and development programs do you do? And when does a subset get so small that you're not going to be able to do a randomized trial?"
Advances in genomics has allowed drugmakers to develop not just a new breast cancer treatment, for example, but one that targets a specific genotype of that cancer like HER2, as was done with trastuzumab (Herceptin).
Anywhere from an eighth to half of companies' drug pipelines are targeted therapies, Woodcock said. About a third of new entities approved by the FDA last year had some type of genotyped biomarker in its marketing application.
Developments in cancer drugs, infectious diseases, and genetic disorders have led the way on such personalized therapies.
But in order to develop trials to test these drugs, the FDA and drug developers need a "new definition of clinical trials" that recognizes therapies will be targeted at subsets of conventionally defined diseases, Woodcock said.
Rather than doing a single trial in all patients with a particular disease, developers need to stratify patients into needed subsets based on certain biomarkers, she continued. Only then will trials be able to test the safety and effectiveness of their drug candidates.
The way trials were developed in the past should not influence or govern the way things are done in the future, Woodcock said.
For decades, the agency has requested two randomized, controlled, non-inferiority trials. But those may not be possible with the small number of patients possible in trials.
In order to identify these subset of patients -- which may be very few in number -- drugmakers may have to work together or work with third parties like patient advocacy groups to identify them, the FDA drug center head said.
"We haven't seen a lot of this so far," Woodcock said. "We're hoping that independent groups set up these trial networks and standing trials, so that then companies are comfortable coming together through a third party to do development of their drugs."
The personalized cystic fibrosis drug ivacaftor (Kalydeco), which treats the disease arising from the G551D-CFTR mutation, was developed through such a patient group network, Woodcock said.
But there are other challenges the agency and developers must tackle too.
Such targeted therapies have had difficulty receiving insurance coverage, in part because of their price. Woodcock noted this trend has slowed development of diagnostics that accompany such products.
Therefore, targeted therapies need to slow or stop chronic diseases and not just show a positive short-term benefit to silence critics. "If we can cure Hepatitis C, there's not going to be a peep from anybody because the cost effectiveness of that will be absolutely clear," she said. "Same with cancer."
The FDA is also thinking about how to translate prescribing information to providers, who want simple, easy-to-understand instructions.
"They want directions. They don't want education. They don't want to be taught genetics," Woodcock said. "They want [to know] 'what do I do. please tell me.' "
Therefore, diagnostics that accompany drugs and information in labeling needs to be detailed and accurate but also easily understood.
That path ahead won't be easy and will require a grand change in the way clinical trials are thought about by drug regulators and developers. "We're going into uncharted waters here," Woodcock said. "I think it's going to be a big challenge for everyone."