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European Journal of Clinical Pharmacology

, Volume 75, Issue 9, pp 1193–1200 | Cite as

Regulatory characteristics and pivotal study design of US Food and Drug Administration approval of drugs for major vs. minor cancer

  • Kenji YamashitaEmail author
  • Masayuki Kaneko
  • Mamoru Narukawa
Clinical Trial
  • 74 Downloads

Abstract

Purpose

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.

Methods

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.

Results

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).

Conclusions

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.

Keywords

Drug approval Investigational new drug application Cancer U.S. Food and Drug Administration Expedited development programs 

Notes

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.

Ethical approval

This article does not contain any studies with human participants or animals.

Informed consent

For this study, a formal consent is not required.

References

  1. 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
  2. 2.
    Hwang TJ, Franklin JM, Chen CT, Lauffenburger JC, Gyawali B, Kesselheim AS, Darrow JJ (2018) Efficacy, safety, and regulatory approval of Food and Drug Administration–designated breakthrough and nonbreakthrough cancer medicines. J Clin Oncol 36(18):1805–1812CrossRefGoogle Scholar
  3. 3.
    Pub. L. 97–414 (1983) codified as amended at 21 U.S.C. §§ 360aa - 360eeGoogle Scholar
  4. 4.
    Kesselheim AS, Myers JA, Avorn J (2011) Characteristics of clinical trials to support approval of orphan vs nonorphan drugs for cancer. JAMA 305(22):2320–2326CrossRefGoogle Scholar
  5. 5.
    Surveillance Research Program, National Cancer Institute, SEER*Stat software version 8.3.5 (http://seer.cancer.gov/resources/)
  6. 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. 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
  8. 8.
    Sequist LV, Joshi VA, Jänne PA et al (2007) Response to treatment and survival of patients with non-small cell lung cancer undergoing somatic EGFR mutation testing. Oncologist 12(1):90–98CrossRefGoogle Scholar
  9. 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
  10. 10.
    Fan L, Feng Y, Wan H, Shi G, Niu W (2014) Clinicopathological and demographical characteristics of non-small cell lung cancer patients with ALK rearrangements: a systematic review and meta-analysis. PLoS One 9(6):e100866CrossRefGoogle Scholar
  11. 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
  12. 12.
    Bergethon K, Shaw AT, Ou SH et al (2012) ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol 30(8):863–870CrossRefGoogle Scholar
  13. 13.
    Liu W, Kelly JW, Trivett M, Murray WK, Dowling JP, Wolfe R, Mason G, Magee J, Angel C, Dobrovic A, McArthur GA (2007) Distinct clinical and pathological features are associated with the BRAF(T1799A(V600E)) mutation in primary melanoma. J Invest Dermatol 127(4):900–905CrossRefGoogle Scholar
  14. 14.
    Risch HA, McLaughlin JR, Cole DE et al (2001) Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet 68(3):700–710CrossRefGoogle Scholar
  15. 15.
    Cortes-Ciriano I, Lee S, Park WY, Kim TM, Park PJ (2017) A molecular portrait of microsatellite instability across multiple cancers. Nat Commun 8:15180.  https://doi.org/10.1038/ncomms15180 CrossRefGoogle Scholar
  16. 16.
    Levis M (2013) FLT3 mutations in acute myeloid leukemia: what is the best approach in 2013? Hematology Am Soc Hematol Educ Program 2013:220–226CrossRefGoogle Scholar
  17. 17.
    Zenz T, Benner A, Döhner H, Stilgenbauer S (2008) Chronic lymphocytic leukemia and treatment resistance in cancer: the role of the p53 pathway. Cell Cycle 7(24):3810–3814CrossRefGoogle Scholar
  18. 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. 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. 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

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Clinical Medicine (Pharmaceutical Medicine), Graduate School of Pharmaceutical SciencesKitasato UniversityMinato-kuJapan

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