Before a new drug can get to patients, it goes through years of research and development followed by a series of preclinical and clinical trials and then is subject to what’s often a drawn-out federal approval process.
That whole cycle – which can take an average of 10 to 15 years and cost more than $1 billion – is designed to collect enough safety and efficacy data to protect patients. That’s a lot of money and a long time to wait for a life-saving drug for patients, many of whom die before a new drug comes to market.
Now there’s a new way – called the breakthrough therapy designation – for drugs to get approved through the U.S. Food and Drug Administration and to market in a much quicker way.
To be granted breakthrough potential, an investigational drug must be for life-threatening or serious illness, and early clinical evidence must suggest it will offer substantial improvement over existing therapies. Those drugs that are granted the new status will get special attention from FDA regulators and make it to market without much of the red tape reserved for most pharmaceutical drugs.
“This still maintains the high quality of scientific rigor of the data, but shaves years off the potential development,” said Jeff Allen, executive director of Friends of Cancer Research, a Washington, D.C., patient advocacy group that spearheaded the effort for the new designation.
The group along with drug companies and other supporters pushed for a new designation because they said other approval paths did not take into account the changing nature of science. Scientists now know much more about the molecular biology of diseases and are able to create less toxic and more effective treatments, so researchers and patient groups said the FDA needed to reflect that and offer more flexibility in its approval process.
The new status was included in the FDA Safety and Innovative Act of 2012, a law which was created 20 years ago and is updated every five years. Drugs started receiving the designation in January.
None of those drugs has been approved yet, so it’s unclear how much time will be shaved off the process. But supporters estimate it will shorten the process by months or even years. The first drugs through this pipeline are expected to hit the market before the end of the year.
Drug companies are clearly interested in the new option. As of mid-July, the FDA had granted breakthrough status to 24 of the 67 experimental therapies that applied for the designation. The agency rejected 18 others and is considering the rest.
The 24 drugs with breakthrough status would treat a range of illnesses, including cancer, hepatitis, cystic fibrosis and muscular dystrophy. Genentech received breakthrough status in May for an investigational medicine to treat leukemia. The drug may be among the first to get approved under the new designation.
The FDA in recent years has already been stepping up its approval of novel therapies, or the type of new drugs that could be considered candidates for breakthrough status. Without the new designation, the FDA had approved 18 such drugs in 2007, 22 in 2008, 26 in 2009, 21 in 2010, 30 in 2011 and 39 last year.
“Having 24 approvals in the midway of the calendar year is showing there’s a lot of interest among the companies and there’s willingness on the part of the FDA (to speed up the process), so it’s pretty exciting,” said Allen of Friends of Cancer Research.
Drug companies and patient groups said the new status may compress the timeline but doesn’t put patients at risk because the same standards for safety and effectiveness apply. “This still maintains the high quality of scientific rigor of the data, but shaves years off the potential development,” Allen said.
Breakthrough status isn’t the only way a drug company can get its candidate through the FDA bureaucracy with less hassle.
Back in 1992, the FDA initiated its Priority Review program, which shortened the review of the final-stage application before the drug goes to market by four months – from the standard 10 months to six months.
Other paths – Fast Track and Accelerated Approval – followed, all designed to reduce the time it takes for new medications to get to patients who don’t have many options.
So why the need for yet another category? Breakthrough proponents say a new status was needed because scientific advancements have changed the way drugs are developed, creating the need for more flexibility in the regulatory process.
Many of the newer treatments for cancer and other conditions, for example, can home in on specific disease “targets” – mutations or other anomalies – and advanced testing can predict which patients are more likely to benefit from the drug than others.
That newer, more personalized approach may reduce the need for the standard, lengthy clinical trial process that traditionally starts with a very small research trial that tests the drug’s toxicity and then gradually moves into larger trials involving more patients.
“The science has advanced so we have better understanding of how to target different mechanisms and select patients, so the effect is we’re seeing are sooner and larger results,” said Allen, of Friends of Cancer Research. “That allows us to alter the approval process.”
Breakthrough status gives the FDA and the drug’s sponsor more leeway in designing trials – such as folding the first two phases of the trials into just one – and allows the drug’s researchers and FDA scientists to communicate with each other throughout the process, rather than just at the end.
Researchers point to new drugs like Genentech’s Zelboraf for melanoma, the most deadly form of skin cancer, and Pfizer’s lung cancer drug Xalkori and the type of treatments that helped drive the need for a new approval process.
Had both of those drugs not been approved before breakthrough status’ creation, health experts say those therapies could have been prime candidates for the new designation. They showed strong results early in the trial process and went after specific targets so it was clear which patients were most likely to benefit.
Recalls AIDS response
Michelle Rohrer, vice president of U.S. regulatory affairs for Genentech, likens the need for the quicker timelines to the AIDS crisis of the 1980s when public outrage spurred the development of new treatments. The promising results of the drugs prompted manufacturers and regulators to work together and get them to the public with unprecedented speed.
“With the AIDS epidemic, there was this all-hands-on-deck kind of feeling,” she said. “If we did it for AIDS, shouldn’t we be doing it for all conditions where there’s an urgent need?”
Officials from the California Healthcare Institute, a research and advocacy organization for the state’s biomedical industry, fear the forced federal spending cuts known as sequestration will hold back drug development, even with this new status.
Drug companies agreed to pay higher fees under last year’s FDA Safety and Innovation Act, the law that included the breakthrough designation. But a portion of those funds – estimated at $85 million – is being held back under sequestration.
Todd Gillenwater, the group’s senior vice president of public policy, said the effects haven’t been felt yet, but they will be.
Gillenwater said it’s frustrating because faster drug development could save money by staving off or possibly curing complicated, progressive diseases like Alzheimer’s that use tremendous amounts of medical resources.
“If we are able to bring safe and effective treatments to patients who need them quicker, not only will patients be affected,” he said. “It also, frankly, helps address some of these big picture, big dollar challenges our health care system is facing.”
New ‘breakthrough’ drugs
What is the new breakthrough therapy designation? It’s a way for drugs that treat serious, life-threatening illnesses to get approved through the U.S. Food & Drug Administration. Preliminary clinical evidence must suggest these so-called breakthrough therapies provide a substantial improvement over existing treatments.
Are there other expedited FDA review tracks? Yes. The FDA already has “priority review,” “accelerated approval” and “fast track” designations, all designed to provide a speedier path over standard FDA reviews. But “breakthrough” combines some of the features of those faster designations while offering additional flexibility early in the drug development process.
How much faster will breakthrough get drugs to the public? That remains to be seen because no new drugs have been approved under the new law, which was passed last year. The FDA started designating drugs under the new status in January.
For more information, go to http://1.usa.gov/nRrB1.