FDA's Breakthrough Therapy Designation Aims to Speed Drug Approvals

A new Food and Drug Administration (FDA) method for speeding drug development holds promise primarily for therapies that carry early and striking benefits for patients whose diseases lack adequate treatments or have none at all, investigators say.

“It‘s really for drugs that appear to be lifesaving,” says Wyndham Wilson, head of the National Cancer Institute’s lymphoma therapeutics section, referring to the “breakthrough therapy“ designation. The designation was signed into law as part of the Food and Drug Administration Safety and Innovation Act in July 2012.

As the name implies, this act reflects the federal agency’s recognition that some treatments offer such obvious benefits to patients early in development that there might be no need for traditional, large-scale clinical trials. As scientists continue unraveling the molecular underpinnings of disease, drugs can also be approved in advance, pending the results from larger trials. Key to the new designation, however, is frequent, “hands-on” interaction between the FDA and drug developers to ensure patient safety as a drug moves closer to possible approval.

Such intense guidance during the drug approval process distinguishes breakthrough therapy status from other FDA avenues for streamlining approval of important drugs, according to Wilson. “Breakthrough therapy designation has more to do with how the FDA engages a company rather than different mechanisms,” he says, with the agency helping, for example, to design smaller, more efficient studies to validate—or not—a dramatic, early finding.

Other mechanisms include fast-track designation, accelerated approval and priority review—all designed to shorten the standard drug review process. The fast-track designation also speeds drug development for serious or life-threatening diseases while the accelerated approval process allows drugs to gain approval based on preliminary data, pending completion of confirmatory studies. Priority review can shorten review time from 10 months to six.

Wilson predicts limited use of this newest designation, however. So far, the FDA has granted breakthrough therapy designation to 31 novel agents out of 92 requests made by the industry, with two approvals so far. (See Pipeline items about Gazyva [obinutuzumab] and Imbruvica [ibrutinib].) Sometimes the FDA requires follow-up confirmation trials.

Otis W. Brawley, chief medical officer of the American Cancer Society, predicts the breakthrough therapy designation will be reserved primarily for drugs that exhibit a “Lazarus effect.” That’s when seriously ill patients who’ve exhausted treatment options “suddenly get out of bed” after receiving a new drug.

The rapid emergence of molecular markers is credited, in part, with driving creation of the breakthrough therapy designation. But, another important factor, Brawley says, is the difficulty in accruing sufficient numbers of patients with rare diseases or uncommon genetic markers for large clinical trials.

“With targeted therapies, we are seeing unprecedented effects very early in development,” says Jeff Allen, a molecular biologist and executive director of Friends of Cancer Research, an advocacy group in Washington, D.C., that pushed for the breakthrough therapy designation. “But how much time might be shaved off (the development process) must be looked at on a case-by-case basis.”

Similarly, the magnitude of an effect seen early on will vary by disease type with no “set bar” at this point, Allen says.

“What we’re hoping for with this designation is there will be early collaboration with FDA, not just for clinical trials but all facets of drug development,” he says. “The designation is to start that conversation.”