One exciting component of the Food and Drug Administration Safety and Innovation Act was the creation of the breakthrough therapy designation. It allows an all-hands-on-deck approach at the FDA to determine the best path forward when the early clinical promise of a drug is so significant and meaningful beyond existing therapies — or lack of other meaningful therapies — for serious or life-threatening illnesses. Although the validity of the breakthrough designation was questioned recently in a tone-deaf article in the New England Journal of Medicine, this designation has provided patients with tremendous benefit since it was passed into law in 2012.
First, drugs that receive the breakthrough therapy designation are developed significantly faster than those that don’t. A 2016 analysis by my organization, Friends of Cancer Research, found that breakthrough-designated drugs were developed more than two years faster than non-designated drugs. This difference in development time is substantial and increases access to new therapies among patients with serious or life-threatening diseases.
The designation has also resulted in a more streamlined drug-review process. Collaboration between the FDA and the product developer takes place earlier and with fewer delays. In the past, extremely promising drugs were often held up in what was then a more protracted process.
The breakthrough therapy designation also addresses the unmet needs of millions patients with serious illnesses. The designation has been granted to drugs for many conditions that have few, if any, effective treatment options. These include a spectrum of rare inherited disorders, pediatric cancers, adult cancers in highly refractory populations, and infectious diseases. Every day counts for patients with these conditions who are waiting for the chance to try a new treatment — the median three months saved during FDA review and the previously noted improvement in development time are not inconsequential for them.
As described in the law authorizing the designation, it “takes steps to minimize” patient exposure to less-effective treatments. When a drug shows very strong improvement over existing treatment options, it may at times be unethical to conduct a randomized trial in which patients are assigned to a treatment arm with an unambiguously inferior treatment option. The breakthrough designation solves this problem by allowing the product developer to discuss its data early in clinical development with the FDA and collaboratively determine the best trial design for patients.
One breakthrough drug, for example, had effects that were so clear and dramatic that doctors demanded that a clinical trial of it remain open so as many of their patients as possible could continue to receive the treatment. This led to the development of an expanded drug trial design and patients receiving earlier access to treatment.
The NEJM article by Jonathan J. Darrow and his colleagues at Harvard Medical School was numb to both the actual patient experience and how patients may define a significant advance over an existing therapy. They argued that the FDA’s definition of all existing therapies allows drugs to be granted approval without showing benefit over appropriate comparators. If the FDA were to change how it views existing therapies, as Darrow and colleagues suggest, many drugs would be blocked from receiving the breakthrough designation, creating a bottleneck and limiting the benefits of the program to fewer drugs and, more importantly, to fewer patients.
An argument some have made against the breakthrough therapy designation is that many drugs granted it have shown limited complete response rates— meaning no detectable sign of cancer remains — despite encouraging overall response rates. Although complete response is an audacious endpoint, a drug can still have a meaningful clinical benefit, including significantly extended survival, without completely obliterating all signs of cancer. It’s unrealistic to use that as the sole indicator of a good drug.
All programs benefit from being evaluated from time to time. The breakthrough therapy designation is no different. The FDA and stakeholders have continued to evaluate the program. The agency has streamlined the application process, found ways in which the designation can promote more efficient clinical trials, and has fully acknowledged the resource-intensive nature of the program, which was subsequently bolstered with an increased allocation to the program by Congress during the last Prescription Drug User Fee Act reauthorization.
The breakthrough therapy designation is an essential FDA program intended to speed access to lifesaving drugs for the patients who need them most. It has already had a profound impact on expediting the delivery of many highly effective new drugs, allowing patients to access them sooner than previously possible. We must not lose sight of the benefits and the positive impact this program has already brought to a multitude of patients and will continue to do so.