Regulatory characteristics and pivotal study design of US Food and Drug Administration approval of drugs for major vs. minor cancer
- 71 Downloads
We aimed to investigate the regulatory approval of drugs for cancers by the US Food and Drug Administration based on the cancer type (major vs. minor), including the use of expedited development programs and duration from Investigational New Drug application (IND) to marketing approval.
From publicly available records and through a Freedom of Information Act request, we gathered data to evaluate regulatory characteristics and pivotal study design for 115 anticancer drug approvals between 2012 and 2017 and the data were analyzed based on cancer incidence (major vs. minor cancers) and how expedited programs, orphan drug designation, and pivotal study design contribute to expedited approval was studied.
Drugs targeting minor cancers more frequently (67%; P = 0.0155) utilized breakthrough therapy designation and/or accelerated approval, both of which significantly contributed to expedited drug approval (median time from IND to approval, 6.4 years; P = 0.0008, 6.2 years; P < 0.0001). Drug approvals for pivotal study design without a comparator arm took significantly less time from IND to approval (median time from IND to approval, 6.2 years; P < 0.0001).
Drugs targeting minor cancers have frequently utilized the expedited development programs; thus, efficiently shortening time to approval. As many of such drugs are approved based on non-comparative pivotal studies, meticulous evaluation and follow-up should be performed for such drugs after their approval.
KeywordsDrug approval Investigational new drug application Cancer U.S. Food and Drug Administration Expedited development programs
Compliance with ethical standards
Conflict of interest
Kenji Yamashita is an employee of MSD K.K. (a subsidiary of Merck & Co., Inc., Kenilworth, N.J., USA). Masayuki Kaneko declares that he has no conflict of interest. Mamoru Narukawa declares that he has no conflict of interest.
This article does not contain any studies with human participants or animals.
For this study, a formal consent is not required.
- 1.US Food and Drug Administration. Guidance for industry. Expedited programs for serious conditions - drugs and biologics. https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf. Accessed 13 October 2018
- 3.Pub. L. 97–414 (1983) codified as amended at 21 U.S.C. §§ 360aa - 360eeGoogle Scholar
- 5.Surveillance Research Program, National Cancer Institute, SEER*Stat software version 8.3.5 (http://seer.cancer.gov/resources/)
- 6.Surveillance, Epidemiology, and End Results (SEER) Program (http://www.seer.cancer.gov) SEER*Stat Database. Incidence - SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2016 Sub (2000–2014) <Katrina/Rita Population Adjustment> − Linked To County Attributes - Total U.S., 1969–2015 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, released April 2017, based on the November 2016 submission
- 7.Goldenberg G, Karagiannis T, Palmer JB, Lotya J, O’Neill C, Kisa R, Herrera V, Siegel DM (2016) Incidence and prevalence of basal cell carcinoma (BCC) and locally advanced BCC (LABCC) in a large commercially insured population in the United States: a retrospective cohort study. J Am Acad Dermatol 75(5):957–966CrossRefGoogle Scholar
- 9.Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA, AURA3 Investigators (2017) Osimertinib or platinum–pemetrexed in EGFR T790M–positive lung cancer. N Engl J Med 376(7):629–640CrossRefGoogle Scholar
- 11.Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB (2016) Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387(10027):1540–1550CrossRefGoogle Scholar
- 18.National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: acute lymphoblastic leukemia, version 1.2018. [Online]. Available: http://www.nccn.org. Accessed 30 September 2018
- 19.National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: pancreatic adenocarcinoma, version 2.2018. Available: http://www.nccn.org. Accessed 14 October 2018
- 20.National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: acute myeloid leukemia, version 2.2018. http://www.nccn.org. Accessed 30 September 2018