FDA 'Breakthrough' Drug Program

The U.S. Food and Drug Administration (FDA) has long been criticized by pharmaceutical companies and patient advocates for taking too long to approve new drugs. But the agency had something to brag about this July as it announced the approval of the fifth and sixth drugs to come through a new process for so-called "breakthrough therapies," first introduced in 2012.

Experts and drug company representatives described the breakthrough drugs program as similar to previous FDA efforts to expedite approval “on steroids.”

The FDA faces a constant tug-of-war between taking too long to approve new drugs and vetting them too quickly, leaving the door open for troublesome risks or side effects when a wider population begins taking the medications.

Most complaints about how long it takes to release a new nasal spray or erectile dysfunction medication come from pharmaceutical companies. However, the slow approval of drugs that could extend the lives of terminally ill patients can also set public anger simmering.

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New Program for Potentially Life-Saving Drugs

The breakthrough therapy designation creates a way for drugs that treat serious and life-threatening diseases to get through the FDA’s approval process faster. One of the recently OK'd drugs flew through its paces for one of two approved uses in less than four months, which is light speed for a regulatory agency like the FDA.

A drug candidate can be designated a breakthrough therapy if it treats a serious or life threatening disease and appears, in early clinical studies, to offer a major improvement over current treatments.

Three of the drugs that have come to market through the breakthrough program treat chronic lymphocytic lymphoma. One treats lung cancer; one, cystic fibrosis; and one is the new hepatitis C treatment sofosbuvir (Sovaldi).

The designation comes with more informal guidance for drug makers, including an FDA case manager to help guide the company through any snags along the way.

“You have to think about drug approval as a very complicated project that has many dimensions,” said Urte Gayko, the senior vice president of global regulatory affairs at Pharmacyclics, a California company that has produced two FDA breakthrough drugs.

“Measures like breakthrough therapies are beneficial because they help FDA focus its resources on the drugs that are most needed; the ones for serious and life-threatening conditions and that are going to be better than what’s on the market,” —Patricia Zettler

Being labeled a "breakthrough" may also allow drugs to enter the FDA’s accelerated approval pipeline, created in 1992. The accelerated approval process lets drugs go to market based on a clinical data point, such as tumor growth rate or blood cell count, likely to result in longer survival or improved health, rather than on a direct measure of those outcomes. The FDA reserves the right to revoke the approval if further testing doesn’t confirm the drug's benefits.  

Three of the six approved breakthrough drugs have also taken advantage of accelerated approval. But it’s the individual attention that seems to do most to speed up the process, Gayko said.

“We don’t want drugs to be either held up or completely not approved because of a simple lack of communication or a technical issue with the application," said Mark Fleury, a principal in policy development and emerging science at the American Cancer Society’s lobbying arm, the Cancer Action Network. “You want these drugs to be judged on their merits, their scientific evidence. I think that the breakthrough therapy designation ensures that we’re really focusing on the science and the data.”

Patient advocates say speedier drug approval processes help ensure that good drugs get through the FDA’s process quickly.

“Measures like breakthrough therapies are beneficial because they help FDA focus its resources on the drugs that are most needed; the ones for serious and life-threatening conditions and that are going to be better than what’s on the market,” former regulator Patricia Zettler, now a fellow at Stanford’s Center for Law and the Biosciences, told Healthline.

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Speed Brings Risks, Too

But there are risks to faster approval and less strict requirements about what clinical studies must prove. Doctors and regulators are all too aware of these risks, but public sentiment — driven by patients desperate to do something, anything to combat life-threatening illnesses — can sometimes override these fears.

“There’s a lot of discussion out there about getting new drugs approved quicker and getting new drugs approved more efficiently, but I don’t think there is a lot of discussion about what some of the real risks of those kinds of inclinations are,” said Dr. Aaron Kesselheim, an expert on drug development at Harvard Medical School.

In 2011, the FDA pulled its tentative accelerated approval of bevacizumab (Avastin) for use in breast cancer patients after concluding that the drug didn’t improve survival rates.

But when patients showed up to a hearing on the decision, they didn’t object to the risks they’d faced. Instead, they pleaded with regulators not to pull the drug because they believed it had helped them.

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In the two decades since the FDA rolled out accelerated approval, it has pulled just a handful of other drugs. That suggests that the program doesn’t grease the tracks beyond what’s prudent. But could the new breakthrough therapy program?

Representatives of one of the drug companies behind a new breakthrough drug jokingly complained that the process was so fast they had to rush their own research to keep up with the FDA, Fleury said.

“You want to get rid of the fat in the process, but you cannot cut the bone of good scientific evidentiary review,” he said.

How Will the FDA Assign 'Breakthrough' Label?

It’s too early to tell for sure if the FDA has finally found the right way to evaluate potentially game-changing drugs for very sick patients.

The biggest test, according to Kesselheim, will be which drugs earn the time-saving designation as time goes on.

“If it’s applied in very limited, judicious fashion to true breakthroughs, then patients benefit and that’s the most important thing," he said. "If it is applied in a fashion where anything is considered a breakthrough or a fashion where invalidated and risky endpoints are used in studies then it will harm patients. It’s a very case-specific assessment that needs to be made."

The FDA, which is largely funded by user fees paid by pharmaceutical companies, faces incentives to help the companies start selling their products sooner. 

But with the first handful of breakthrough drugs approved to treat blood cancer, hepatitis C, and cystic fibrosis, all sides say the program shows early signs of success.

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