[Skip to Content]
[Skip to Content Landing]

A 25-Year Experience of US Food and Drug Administration Accelerated Approval of Malignant Hematology and Oncology Drugs and BiologicsA Review

Educational Objective
To learn the outcome of the US Food and Drug Administration Accelerated Approval program for Malignant Hematology Oncology Drugs and Biologics.
1 Credit CME
Abstract

Importance  Accelerated approval (AA) is a US Food and Drug Administration (FDA) expedited program intended to speed the approval of drugs and biologics that may demonstrate a meaningful advantage over available therapies for diseases that are serious or life-threatening.

Observations  This review describes all malignant hematology and oncology AAs from inception of the program on December 11, 1992, to May 31, 2017. During this period, the FDA granted AA to 64 malignant hematology and oncology products for 93 new indications. Of these AAs, 53 were for new molecular entities. Overall, the end point of response rate, including hematologic response rates, accounted for most AAs (81 [87%]), followed by time-to-event end points of progression-free survival or time to progression (8 [9%]) and disease-free survival or recurrence-free survival (4 [4%]). Single-arm trial designs provided the data for 67 (72%) of the initial AA indications. Of the 93 AAs, 51 (55%) have fulfilled their postmarketing requirement and verified benefit in a median of 3.4 years after their initial AA. Thirty-seven (40%) indications have not yet completed confirmatory trial(s) or verified benefit, and 5 indications receiving AA (5%) have been withdrawn from the market.

Conclusions and Relevance  The use of the AA program during the past 25 years has increased over time, and only a small portion of indications under the AA program fail to verify clinical benefit. For patients with serious or life-threatening oncologic diseases, AA brings products to the market years before confirmatory trials are typically completed.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

Article Information

Accepted for Publication: November 28, 2017.

Corresponding Author: Julia A. Beaver, MD, Office of Hematology and Oncology Products, US Food and Drug Administration, 10903 New Hampshire Ave, Building 22, Room 2100, Silver Spring, MD 20993 (julia.beaver@fda.hhs.gov).

Published Online: March 1, 2018. doi:10.1001/jamaoncol.2017.5618

Author Contributions: Drs Beaver, Howie, and Pelosof contributed equally to this work. Drs Beaver and Kluetz had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Beaver, Kim, Blumenthal, Pazdur, Kluetz.

Acquisition, analysis, or interpretation of data: Beaver, Howie, Pelosof, Kim, Liu, Goldberg, Sridhara, Blumenthal, Farrell, Keegan, Kluetz.

Drafting of the manuscript: Beaver, Howie, Pelosof, Liu, Blumenthal, Farrell, Pazdur, Kluetz.

Critical revision of the manuscript for important intellectual content: Beaver, Howie, Pelosof, Kim, Goldberg, Sridhara, Blumenthal, Farrell, Keegan, Kluetz.

Statistical analysis: Howie, Liu.

Administrative, technical, or material support: Beaver, Howie, Kim, Goldberg, Sridhara, Keegan, Pazdur.

Study supervision: Beaver, Kim, Blumenthal, Farrell, Pazdur, Kluetz.

Conflict of Interest Disclosures: The authors conducted all work on the manuscript during their work at the US Food and Drug Administration. No additional funds were used for this activity.

References
1.
Code of Federal Regulations. §21-314.126. https://www.ecfr.gov/cgi-bin/text-idx?SID=8eea61dec0ef9b17f1fa0d0d3a7736c6&mc=true&node=se21.5.314_1126&rgn=div8. March 4, 2002. Accessed September 13, 2017.
2.
Code of Federal Regulations. §314.510. https://www.ecfr.gov/cgi-bin/text-idx?SID=7e3afa31ba9326a86c1c08ca7cb22f4c&mc=true&node=se21.5.314_1510&rgn=div8. December 11, 1992. Accessed September 13, 2017.
3.
Code of Federal Regulations. §601.41. https://www.ecfr.gov/cgi-bin/text-idx?SID=c03234aa22abbed0380923a4cc6ab001&mc=true&node=se21.7.601_141&rgn=div8. December 11, 1992. Accessed September 13, 2017.
4.
Food and Drug Administration Safety and Innovation Act, 21 USC §301. https://www.gpo.gov/fdsys/pkg/PLAW-112publ144/pdf/PLAW-112publ144.pdf. July 9, 2012. Accessed September 13, 2017.
5.
US Food and Drug Administration. Guidance for Industry: Expedited Programs for Serious Conditions–Drugs and Biologics. May 2014. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf. Accessed September 13, 2017.
6.
US Food and Drug Administration. Center for Drug Evaluation and Research, Oncologic Drugs Advisory Committee (ODAC) [meeting transcript]. February 8, 2011. https://wayback.archive-it.org/7993/20170404153747/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM245644.pdf. Accessed September 13, 2017.
7.
Dagher  R, Johnson  J, Williams  G, Keegan  P, Pazdur  R.  Accelerated approval of oncology products: a decade of experience.  J Natl Cancer Inst. 2004;96(20):1500-1509.PubMedGoogle ScholarCrossref
8.
Johnson  JR, Ning  YM, Farrell  A, Justice  R, Keegan  P, Pazdur  R.  Accelerated approval of oncology products: the Food and Drug Administration experience.  J Natl Cancer Inst. 2011;103(8):636-644.PubMedGoogle ScholarCrossref
9.
US Food and Drug Administration. Drugs@FDA: FDA approved drug products. http://www.accessdata.fda.gov/scripts/cder/daf/. Accessed March 15, 2017.
10.
Johnson  JR, Williams  G, Pazdur  R.  End points and United States Food and Drug Administration approval of oncology drugs.  J Clin Oncol. 2003;21(7):1404-1411.PubMedGoogle ScholarCrossref
11.
Naci  H, Smalley  KR, Kesselheim  AS.  Characteristics of preapproval and postapproval studies for drugs granted accelerated approval by the US Food and Drug Administration.  JAMA. 2017;318(7):626-636.PubMedGoogle ScholarCrossref
12.
Kesselheim  AS, Woloshin  S, Eddings  W, Franklin  JM, Ross  KM, Schwartz  LM.  Physicians’ knowledge about FDA approval standards and perceptions of the “breakthrough therapy” designation.  JAMA. 2016;315(14):1516-1518.PubMedGoogle ScholarCrossref
13.
Schwartz  LM, Woloshin  S.  Communicating uncertainties about prescription drugs to the public: a national randomized trial.  Arch Intern Med. 2011;171(16):1463-1468.PubMedGoogle ScholarCrossref
14.
US Food and Drug Administration. Guidance for Industry: Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics. May 2007. https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm071590.pdf. Accessed September 13, 2017.
15.
Blumenthal  GM, Kluetz  PG, Schneider  J, Goldberg  KB, McKee  AE, Pazdur  R.  Oncology drug approvals: evaluating endpoints and evidence in an era of breakthrough therapies.  Oncologist. 2017;22(7):762-767.PubMedGoogle ScholarCrossref
16.
Blumenthal  GM, Pazdur  R.  Response rate as an approval end point in oncology: back to the future.  JAMA Oncol. 2016;2(6):780-781.PubMedGoogle ScholarCrossref
17.
Califf  RM.  Balancing the need for access with the imperative for empirical evidence of benefit and risk.  JAMA. 2017;318(7):614-616.PubMedGoogle ScholarCrossref
18.
Kazandjian  D, Blumenthal  GM, Chen  HY,  et al.  FDA approval summary: crizotinib for the treatment of metastatic non-small cell lung cancer with anaplastic lymphoma kinase rearrangements.  Oncologist. 2014;19(10):e5-e11.PubMedGoogle ScholarCrossref
19.
Kluetz  PG, Chingos  DT, Basch  EM, Mitchell  SA.  Patient-reported outcomes in cancer clinical trials: measuring symptomatic adverse events with the National Cancer Institute’s patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).  Am Soc Clin Oncol Educ Book. 2016;35:67-73.PubMedGoogle ScholarCrossref
20.
Kluetz  PG, Papadopoulos  EJ, Johnson  LL,  et al.  Focusing on core patient-reported outcomes in cancer clinical trials: response.  Clin Cancer Res. 2016;22(22):5618.PubMedGoogle ScholarCrossref
21.
FDA approves Mylotarg for treatment of acute myeloid leukemia [press release]. Silver Spring, MD: US Food and Drug Administration; September 1, 2017. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574507.htm. Accessed September 25, 2017.
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_LoginSubscribe_Purchase
Close
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_LoginSubscribe_Purchase
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
Close
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
jn-learning_Modal_SaveSearch_NoAccess_Purchase
Close

Lookup An Activity

or

Close

My Saved Searches

You currently have no searches saved.

Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close