Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's "breakthrough therapy" designation is not intended to imply that a drug is actually a "breakthrough" or that there is high-quality evidence of treatment efficacy for a particular condition; rather, it allows the FDA to grant priority review to drug candidates if preliminary clinical trials indicate that the therapy may offer substantial treatment advantages over existing options for patients with serious or life-threatening diseases. The FDA has other mechanisms for expediting the review and approval process for promising drugs, including fast track designation, accelerated approval, and priority review.
A breakthrough therapy designation can be assigned to a drug if "it is a drug which is intended alone or in combination with one or more other drugs to treat a serious or life threatening disease or condition" and if the preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development."
Requests are reviewed by the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER). CDER receives approximately 100 requests per year for breakthrough designation. Historically, about one third were approved. CBER receives 15–30 requests per year. Sponsors must apply for breakthrough status separately for each indication they intend to label the drug for.
Drugs that have been granted breakthrough status are given priority review. The FDA works with the sponsor of the drug application to expedite the approval process. This expedited process can include rolling reviews, smaller clinical trials, and alternative trial designs.
Critics have said that the name is misleading and provides companies that obtain a breakthrough designation for a drug candidate with a marketing advantage that may be undeserved.  The FDA acknowledges that the name "breakthrough therapy" may be misleading. It was never meant to imply that these drugs are actually “breakthroughs,” and it does not ensure that they will provide clinical benefit, but still critics complain that they are based on preliminary evidence, including changes in surrogate markers such as laboratory measurements, that often don't reflect "meaningful clinical benefit." The FDA guidance states: "Not all products designated as breakthrough therapies ultimately will be shown to have the substantial improvement over available therapies suggested by the preliminary clinical evidence at the time of designation. If the designation is no longer supported by subsequent data, FDA may rescind the designation."
- List of drugs granted breakthrough therapy designation
- FDA Fast Track Development Program
- Priority review (FDA)
- Orphan drug
- Darrow, JJ; Avorn, J; Kesselheim, AS (27 March 2014). "New FDA breakthrough-drug category—implications for patients". The New England Journal of Medicine. 370 (13): 1252–8. doi:10.1056/nejmhle1311493. PMID 24670173.
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- Kepplinger EE (February 2015). "FDA's Expedited Approval Mechanisms for New Drug Products". Biotechnol Law Rep. 34 (1): 15–37. doi:10.1089/blr.2015.9999. PMC 4326266. PMID 25713472.
The fourth expedited approval mechanism—the Breakthrough Therapy designation—applies to a new drug product if it "is intended, alone or in combination with 1 or more other drugs, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on 1 or more clinically significant endpoints."172 In its Final Guidance, FDA has interpreted "preliminary clinical evidence" to mean evidence "sufficient to indicate that the drug may demonstrate substantial improvement in effectiveness or safety over available therapies, but in most cases is not sufficient to establish safety and effectiveness for purposes of approval."173 This generally will require more than data from in vitro studies or animal models.174 FDA expects preliminary clinical evidence to come from Phase 1 or 2 clinical trials.175
- "Fact Sheet: Breakthrough Therapies". United States Food and Drug Administration. 10 December 2014. Archived from the original on 9 October 2017. Retrieved 9 October 2017.
A breakthrough therapy is a drug:
• intended alone or in combination with one or more other drugs to treat a serious or life threatening disease or condition and
• preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.
- "Archived copy". Archived from the original on 21 January 2017. Retrieved 3 January 2017.CS1 maint: archived copy as title (link)
- Food and Drug Administration Safety and Innovation Act (FDASIA), Silver Spring, MD: Food and Drug Administration, 29 January 2015, archived from the original on 18 July 2015, retrieved 20 July 2015
- Research, Center for Drug Evaluation and. "IND Activity Reports - Breakthrough Therapy Designation Requests". www.fda.gov.
- Research, Center for Drug Evaluation and (10 April 2019). "Expedited Programs for Serious Conditions––Drugs and Biologics". U.S. Food and Drug Administration.
- Joseph S. Ross; Rita F. Redberg (21 September 2015). "Editor's Note: Would a Breakthrough Therapy by Any Other Name Be as Promising?". JAMA Intern. Med. 175 (11): 1858–9. doi:10.1001/jamainternmed.2015.5311. PMID 26390064.
- Jonathan J. Darrow; Jerry Avorn; Aaron S. Kesselheim (12 April 2018). "The FDA Breakthrough Drug Designation: Four Years of Experience". New England Journal of Medicine. 378 (15): 1444–53. doi:10.1056/NEJMhpr1713338. PMID 29641970.
- "Guidance for Industry Expedited Programs for Serious Conditions – Drugs and Biologics" (PDF). FDA. May 2014. p. 10.