Patients Benefit From Faster FDA Drug Approval Process

Get Permission

Ellen Sigal, PhD

Sandra Horning, MD

Urte Gayko, PhD

Janet Woodcock, MD

There has been remarkable unanimity among FDA reviewers about the appropriateness of breakthrough therapy designation. They almost never disagree about which drugs should make it into the program.

—Janet Woodcock, MD

In an increasing spirit of cooperation, U.S. Food and Drug Administration (FDA) and several pharmaceutical companies are bringing to fruition the newest in a series of ways to expedite drug development and review.

Breakthrough therapy is the designation instituted in 2012 by the FDA Safety and Innovation Act. It is intended for a drug, alone or in combination, to treat a serious or life-threatening disease and for which preliminary clinical evidence indicates substantial improvement over existing therapies on one or more clinically significant endpoints—for example, treatment effects observed early in clinical development. If a sponsor applies for breakthrough designation, FDA will expedite its review and will grant or reject the designation within 60 days.

In early May, the Friends of Cancer Research (FOCR) held a briefing in the Hart Senate Office Building in Washington, DC, to mark the successful launch of the breakthrough designation.1 It was sponsored by Sens. ­Michael ­Bennett (D-CO), Orrin Hatch (R-UT), and Richard Burr (R-NC), who were also the primary sponsors of the original breakthrough legislation, along with Rep. Diana DeGette (D‑CO) and Fmr. Rep. Brian Bilbray (R-CA) in the House.

Progress to Date

In the past 2 years, there have been 184 requests for breakthrough therapy designation. A total of 48 of those requests were granted, and 6 such drugs have been approved:

  • obinutuzumab (Gazyva) from Genentech to treat chronic lympocytic leukemia (CLL)
  • ibrutinib (Imbruvica) from Pharmacyclics/Johnson & Johnson to treat mantle cell lymphoma
  • sofosbuvir (Sovaldi) from Gilead to treat hepatitis C
  • ivacaftor (Kalydeco) from Vertex to treat cystic fibrosis
  • ofatumumab (Arzerra) from Genmab/GlaxoSmithKline to treat chronic lymphocytic leukemia
  • ceritinib (Zykadia) from Novartis to treat non–small cell lung cancer (NSCLC)

In her opening remarks at the briefing, Ellen Sigal, PhD, Chair and Founder of FOCR, said, “The idea for this new designation came from FDA, and there has been a lot of support from that agency and also from manufacturers, Congress, and advocacy groups. Everyone thinks it’s a good thing.”

Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development, Genentech—and former ASCO President, agreed. “We had the first drug approved through this program, for CLL, an incurable and difficult-to-treat cancer that usually occurs in patients aged 70 and over. These patients tend to have other medical conditions that make treatment especially difficult, and many are not candidates for standard combination therapy. Obinutuzumab combined with mild chemotherapy is an important new option for these patients.”

She added that working with FDA in such a speeded-up and intense environment requires a certain mindset, a “can-do” attitude.

Urte Gayko, PhD, Senior Vice President of Global Regulatory Affairs, Pharmacyclics, sponsor of ibrutinib, the second drug approved through the program, added positive feelings about working with FDA in a highly charged and concentrated atmosphere. “Mantle cell lymphoma is a true orphan disease, associated with a life expectancy of only a year or two. Patients are in desperate need of a drug that works, and they need it quickly. The breakthrough program provided that, and FDA was very supportive of our efforts.”

It Can Get Confusing

There are three other ways to expedite drug development, review, and approval, each of which contains subtle differences, which can be confusing.

Fast track is intended to expedite review of drugs that treat serious conditions and fill an unmet medical need. Designation is granted on the basis of preclinical data. The sponsor will have more frequent contact with FDA reviewers than usual and can submit portions of a marketing application before submitting the complete one, known as “rolling review.”

Accelerated approval speeds development of a drug that can provide meaningful therapeutic benefit over available therapies and allows approval based on a surrogate endpoint. Accelerated approval is useful when the course of a disease is long, and it takes an extended amount of time to demonstrate and measure clinical benefit. For these reasons, sponsors are usually required to conduct postmarket studies after approval.

Priority review shortens the review time to 6 months from the standard 10 months. Any drug can be granted priority review.

How Breakthrough Works

If FDA grants a designation of breakthrough therapy, it will provide advantages to the sponsor by:

  • holding frequent meetings with drug reviewers
  • providing advice about the drug’s efficacy as demonstrated by clinical and nonclinical data
  • ensuring that the clinical trial design is practical and appropriate, especially in minimizing the number of patients
  • involving senior agency managers and staff in the collaboration

Since the inception of the program, said Janet Woodcock, MD, Director, FDA Center for Drug Evaluation and Research, “There has been remarkable unanimity among FDA reviewers about the appropriateness of breakthrough therapy designation. They almost never disagree about which drugs should make it into the program.” A bit more problematic has been the need for sponsors to “get their act together” regarding drug manufacture. “They’re used to the approval process taking about 7 years, so the speed with which we’re working surprises them, and they’re having trouble making the drug available.”

What This Means for Patients

Breakthrough therapy can bring drugs to market fast. It has the potential to save lives.

Bayard “Chip” Kennett, advocate and former Congressional staffer, is glad of that. He was diagnosed with stage IV NSCLC at age 31 and had had initial success with standard chemotherapy, which then stopped working.

“My oncologist at Hopkins told me about the trial of [ceritinib] that Novartis was conducting in Philadelphia, and since I was driving to Baltimore from my home in Virginia, it didn’t seem like much more of an effort to go north a few more hours—especially since I was out of options,” he said.

He responded almost immediately and now feels well and believes that the breakthrough drug is keeping him alive.

Dr. Sigal said there are a number of patients who feel the same. “This program is wildly popular, especially in view of the all-hands-on-deck philosophy [significantly more work in a good deal less time] to which both FDA and pharmaceutical companies are committed. However, it is also wildly expensive, and FDA needs a big new chunk of money to support it. There are very sick patients out there waiting for help.”

Nevertheless, she added, the issue is more about curative treatment and improved quality of life than it is about money. “Of course, price is important to patients, but efficacy is at the forefront.”

Dr. Woodcock was equally enthusiastic. “Getting effective drugs to patients is the reason why people work at FDA, and this program has been very inspiring—a serious commitment. We need all the drug development avenues we can think of and are willing to expend as much effort as necessary. Some of the products may not last over the long haul, but it’s worth the work.” ■

Disclosure: Drs. Sigal and Woodcock reported no potential conflicts of interest.  Dr. Horning is an employee of Genentech/Roche and has stock in Roche.


1. Science and Progress at the FDA: A Friends of Cancer Research Congressional Briefing on the Progress of the FDA’s Breakthrough Therapy Program. Washington, DC, May 6, 2014.