Breakthrough therapy

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.^[1]^[2] 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;^[3]^[4] 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.^[4]^[5] The FDA has other mechanisms for expediting the review and approval process for promising drugs, including fast track designation, accelerated approval, and priority review.^[4]^[6]

^ 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.
^ Yandell, Kate (1 January 2016). "Picking Up the Pace". The Scientist.
^ Schwitzer G (13 May 2016). "CBS proclaims 'cancer breakthrough' – doesn't explain what FDA means by that term". Health News Review. Archived from the original on 8 December 2020. Retrieved 9 October 2017.
^ ^a ^b ^c 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.
^ "Frequently Asked Questions: Breakthrough Therapies". Food and Drug Administration. Archived from the original on 21 January 2017. Retrieved 3 January 2017.

[1] 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.

[2] Yandell, Kate (1 January 2016). "Picking Up the Pace". The Scientist.

[healthnews-3] Schwitzer G (13 May 2016). "CBS proclaims 'cancer breakthrough' – doesn't explain what FDA means by that term". Health News Review. Archived from the original on 8 December 2020. Retrieved 9 October 2017.

[pmid25713472-4] 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

[FDA_2012-5] "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.

[6] "Frequently Asked Questions: Breakthrough Therapies". Food and Drug Administration. Archived from the original on 21 January 2017. Retrieved 3 January 2017.

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