21st Century Cures: Making Breakthrough Therapy designations more effective
On April 30, 2014, Rep. Fred Upton (R-MI), chair of the House Energy & Commerce Committee, along with Rep. Diana DeGette (D-CO), launched a multi-pronged, multi-year program known as the 21st Century Cures Initiative.
This collaborative initiative involves many different participants and stakeholders, including the National Institutes of Health (NIH), the FDA, other federal agencies, researchers, academic and at the very center—patients. The broad goal of the initiative is to accelerate the pace of drug and medical device approval in the U.S.
The 21st Century Cures Initiative has many working parts; however, one core focus is “streamlining the drug and device development process” and reforming the regulatory framework that underscores that process.
According to DeGette, “Health research is growing quickly, but the federal drug and device approval apparatus is in many ways the relic of another era. We have dedicated scientists and bold leaders at agencies like the NIH and the FDA, but when our laws don’t keep pace with innovation, we all lose.”
The scope of proposed reforms is extensive, but concrete. Over the coming months, BioPharma Dive will be focusing on various aspects of the 21st Century Cures Initiative, starting with Section 1041—proposed changes to the Breakthrough Therapy Designation.
Amping up the Breakthrough Therapy designation
In 2012, the FDA introduced a new category called “Breakthrough Therapy” designation. This designation was established under the FDA Safety and Innovation Act, with the goal of accelerating the approval process for drugs that are intended to address a serious medical need. In order to be eligible for Breakthrough Therapy designation, a drug must demonstrate evidence of substantial improvement on at least one clinically significant endpoint over other available therapies.
For biopharma companies, obtaining Breakthrough Therapy designation translates into several important benefits, including more intensive guidance from the FDA in the form of greater access to key personnel at the FDA, specific guidance and face-to-face contact. In addition, Breakthrough Therapy designation makes a company eligible for rolling review. Between July 2012 and April 2014, 44 drugs received Breakthrough Therapy designation, and six were approved under this designation.
The 21st Century Cures Initiative team has proposed FDA approval of Breakthrough Therapy-designated drugs even faster—based on sufficiently compelling early-stage clinical safety and effectiveness data. The net effect of this approach would mean bringing drugs to market for patients who may not have the time to wait.
Positive response from industry
The industry’s response to the Section 1041 proposal has been very positive. A spokesperson for the Pharmaceutical Researchers and Manufacturers of America (PhRMA) told BioPharma Dive: “PhRMA has long supported the FDA’s appropriate use of innovative approaches and regulatory flexibility to establish the safety and efficacy of innovative medicines to address unmet medical needs. We strongly supported the passage of the Food and Drug Administration Safety and Innovation Act, which enhanced the authority of FDA to consider appropriate scientific data, methods, and tools, and to expedite development and access to novel treatments for patients with a broad range of serious or life-threatening diseases or conditions.”
Yes, it’s true that the original iteration of the Breakthrough Therapy designation is innovative—and the Cures Initiative is trying to maximize its utility as a mechanism for getting more drugs approved, more quickly—while still providing the necessary oversight to ensure safe, long-term outcomes and maintain the integrity of the drug-approval process. Breakthrough Therapy designation requires that even if a company receives approval before all clinical trial data is collected, trials must continue, including agreed-upon postmarketing surveillance studies. This policy would not change under the Section 1041 proposal.
How a Breakthrough Designation affects women with breast cancer
What does the Breakthrough Therapy approval process look like and why does it matter so much? One example: In mid-August 2014, Pfizer was granted Breakthrough Therapy designation for Ibrance (palbociclib, a drug designed to treat HER2-negative advanced breast cancer. This designation was based on compelling clinical data in which women treated with Ibrance and letrazole had a median progression-free survival (PFS) period of 20.2 months, compared with 10.2 months for patients treated only with letrazole. On February 3, 2015, Ibrance was approved by the FDA—less than six months after receiving Breakthrough Designation status and more than two months ahead of its April 13 PDUFA date.
There is an entire armamentarium of treatments for breast cancer, yet last year, 40,000 women died—while more than 230,000 were diagnosed with breast cancer. A serious unmet medical need? Definitely. By demonstrating to the FDA that Ibrance doubled PFS, Pfizer made the case for its new drug as a breakthrough—something that can ostensibly extend life, providing a specific population of advanced breast cancer patients a much-needed treatment option.
The intention of the architects of the 21st Century Cure Initiative is to contract the time-to-approval for game-changing drugs, such as Ibrance—and to make sure that the patients who could benefit from these drugs, have a chance to benefit before it’s too late.
- Medium How the United States Can Remain the World Leader in Medical Innovation
- The Robert Wood Johnson Foundation Health Policy Brief: Breakthrough Therapy Designation