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Characteristics of trials and regulatory pathways leading to US approval of innovative vs. non-innovative oncology drugs.


Vokinger, Kerstin Noëlle; Kesselheim, Aaron S (2019). Characteristics of trials and regulatory pathways leading to US approval of innovative vs. non-innovative oncology drugs. Health Policy, 123(8):721-727.

Abstract

BACKGROUND
Successful first-generation drugs can be converted with small alterations to "second-generation drugs," which are cheaper to develop and may pose less financial risk for manufacturers due to already validated action mechanism and a well-defined consumer market.
METHODS
We found four classes of cancer drugs for first- and second generation products approved in the US: BCR-ABL tyrosine kinase inhibitors (TKI) for treatment of CML, ALK + TKI for NSCLC, CD20 monoclonal antibodies for CLL, and HER2 monoclonal antibodies for breast cancer. We analyzed the characteristics of the clinical trials and the approval pathways for these 14 drugs.
RESULTS
First-generation and 4 out of 5 s-generation BCR-ABL TKI drugs were granted expedited approval, while all drugs were approved based on single-arm trials. Both ALK + TKI drugs were based on single-arm trials and expedited approval. The first-generation CD20 monoclonal antibody drug was approved based on single-arm trials, and one of the second-generation drugs had pivotal trials that were randomized. All benefited from expedited approval. All HER2 monoclonal antibodies in the sample were based on randomized trials and expedited pathways.
CONCLUSION
Second-generation TKI and monoclonal antibodies were often approved through expedited regulatory pathways and studied in single-arm trials. This helps to facilitate the approval for earlier use by patients, but is also associated with greater risk of post-approval safety-related labeling changes or unanticipated adverse events.

Abstract

BACKGROUND
Successful first-generation drugs can be converted with small alterations to "second-generation drugs," which are cheaper to develop and may pose less financial risk for manufacturers due to already validated action mechanism and a well-defined consumer market.
METHODS
We found four classes of cancer drugs for first- and second generation products approved in the US: BCR-ABL tyrosine kinase inhibitors (TKI) for treatment of CML, ALK + TKI for NSCLC, CD20 monoclonal antibodies for CLL, and HER2 monoclonal antibodies for breast cancer. We analyzed the characteristics of the clinical trials and the approval pathways for these 14 drugs.
RESULTS
First-generation and 4 out of 5 s-generation BCR-ABL TKI drugs were granted expedited approval, while all drugs were approved based on single-arm trials. Both ALK + TKI drugs were based on single-arm trials and expedited approval. The first-generation CD20 monoclonal antibody drug was approved based on single-arm trials, and one of the second-generation drugs had pivotal trials that were randomized. All benefited from expedited approval. All HER2 monoclonal antibodies in the sample were based on randomized trials and expedited pathways.
CONCLUSION
Second-generation TKI and monoclonal antibodies were often approved through expedited regulatory pathways and studied in single-arm trials. This helps to facilitate the approval for earlier use by patients, but is also associated with greater risk of post-approval safety-related labeling changes or unanticipated adverse events.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of General Practice
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Health Policy
Language:English
Date:August 2019
Deposited On:05 Sep 2019 13:14
Last Modified:29 Jul 2020 11:15
Publisher:Elsevier
ISSN:0168-8510
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.healthpol.2019.06.002
PubMed ID:31229275

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