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Initial and supplementary indication approval of new targeted cancer drugs by the FDA, EMA, Health Canada, and TGA.
Invest New Drugs. 2022 08; 40(4):798-809.IN

Abstract

BACKGROUND

Previous research focused on the clinical evidence supporting new cancer drugs' initial US Food and Drug Administration (FDA) approval. However, targeted drugs are increasingly approved for supplementary indications of unknown evidence and benefit.

OBJECTIVES

To examine the clinical trial evidence supporting new targeted cancer drugs' initial and supplementary indication approval in the US, EU, Canada, and Australia.

DATA AND METHODS

25 cancer drugs across 100 indications were identified with FDA approval between 2009-2019. Data on regulatory approval and clinical trials were extracted from the FDA, European Medicines Agency (EMA), Health Canada (HC), Australian Therapeutic Goods Administration (TGA), and clinicaltrials.gov. Regional variations were compared with χ2-tests. Multivariate logistic regressions compared characteristics of initial and supplementary indication approvals, reporting adjusted odds ratios (AOR) with 95% confidence intervals (CI).

RESULTS

Out of 100 considered cancer indications, the FDA approved 96, the EMA 92, HC 86, and the TGA 83 (83%, p < 0.05). The FDA more frequently granted priority review, conditional approval, and orphan designations than other agencies. Initial approvals were more likely to receive conditional / accelerated approval (AOR: 2.69, 95%CI [1.07-6.77], p < 0.05), an orphan designation (AOR: 3.32, 95%CI [1.38-8.00], p < 0.01), be under priority review (AOR: 2.60, 95%CI [1.17-5.78], p < 0.05), and be monotherapies (AOR: 5.91, 95%CI [1.14-30.65], p < 0.05) than supplementary indications. Initial indications' pivotal trials tended to be shorter (AOR per month: 0.96, 95%CI [0.93-0.99], p < 0.05), of lower phase design (AOR per clinical phase: 0.28, 95%CI [0.09-0.85], p < 0.05), and enroll more patients (AOR per 100 patients: 1.19, 95%CI [1.01-1.39], p < 0.05).

CONCLUSIONS

Targeted cancer drugs are increasingly approved for multiple indications of varying clinical benefit. Drugs are first approved as monotherapies in rare diseases with a high unmet need. Whilst expedited regulatory review incentivizes this prioritization, indication-specific safety, efficacy, and pricing policies are necessary to reflect each indication's differential clinical and economic value.

Authors+Show Affiliations

Fifth Department of Medicine, University Hospital Mannheim, Heidelberg University, Mannheim, Germany. danielmichaeli@yahoo.com. Department of Personalized Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, Germany. danielmichaeli@yahoo.com. Department of Health Policy and Medical Technology Research Group - LSE Health, London School of Economics and Political Science, London, UK. danielmichaeli@yahoo.com.Department of Health Policy and Medical Technology Research Group - LSE Health, London School of Economics and Political Science, London, UK.Fifth Department of Medicine, University Hospital Mannheim, Heidelberg University, Mannheim, Germany. Department of Personalized Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, Germany. Division of Personalized Medical Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.Department of Health Policy and Medical Technology Research Group - LSE Health, London School of Economics and Political Science, London, UK.Department of Health Policy and Medical Technology Research Group - LSE Health, London School of Economics and Political Science, London, UK.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

35389145

Citation

Michaeli, Daniel Tobias, et al. "Initial and Supplementary Indication Approval of New Targeted Cancer Drugs By the FDA, EMA, Health Canada, and TGA." Investigational New Drugs, vol. 40, no. 4, 2022, pp. 798-809.
Michaeli DT, Mills M, Michaeli T, et al. Initial and supplementary indication approval of new targeted cancer drugs by the FDA, EMA, Health Canada, and TGA. Invest New Drugs. 2022;40(4):798-809.
Michaeli, D. T., Mills, M., Michaeli, T., Miracolo, A., & Kanavos, P. (2022). Initial and supplementary indication approval of new targeted cancer drugs by the FDA, EMA, Health Canada, and TGA. Investigational New Drugs, 40(4), 798-809. https://doi.org/10.1007/s10637-022-01227-5
Michaeli DT, et al. Initial and Supplementary Indication Approval of New Targeted Cancer Drugs By the FDA, EMA, Health Canada, and TGA. Invest New Drugs. 2022;40(4):798-809. PubMed PMID: 35389145.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Initial and supplementary indication approval of new targeted cancer drugs by the FDA, EMA, Health Canada, and TGA. AU - Michaeli,Daniel Tobias, AU - Mills,Mackenzie, AU - Michaeli,Thomas, AU - Miracolo,Aurelio, AU - Kanavos,Panos, Y1 - 2022/04/07/ PY - 2022/01/25/received PY - 2022/02/25/accepted PY - 2022/4/8/pubmed PY - 2022/7/20/medline PY - 2022/4/7/entrez KW - Accelerated approval KW - Cancer drugs KW - Clinical trial KW - Drug development KW - Drug pricing KW - Indication-specific pricing KW - Orphan KW - Pharmaceutical policy KW - Targeted therapy SP - 798 EP - 809 JF - Investigational new drugs JO - Invest New Drugs VL - 40 IS - 4 N2 - BACKGROUND: Previous research focused on the clinical evidence supporting new cancer drugs' initial US Food and Drug Administration (FDA) approval. However, targeted drugs are increasingly approved for supplementary indications of unknown evidence and benefit. OBJECTIVES: To examine the clinical trial evidence supporting new targeted cancer drugs' initial and supplementary indication approval in the US, EU, Canada, and Australia. DATA AND METHODS: 25 cancer drugs across 100 indications were identified with FDA approval between 2009-2019. Data on regulatory approval and clinical trials were extracted from the FDA, European Medicines Agency (EMA), Health Canada (HC), Australian Therapeutic Goods Administration (TGA), and clinicaltrials.gov. Regional variations were compared with χ2-tests. Multivariate logistic regressions compared characteristics of initial and supplementary indication approvals, reporting adjusted odds ratios (AOR) with 95% confidence intervals (CI). RESULTS: Out of 100 considered cancer indications, the FDA approved 96, the EMA 92, HC 86, and the TGA 83 (83%, p < 0.05). The FDA more frequently granted priority review, conditional approval, and orphan designations than other agencies. Initial approvals were more likely to receive conditional / accelerated approval (AOR: 2.69, 95%CI [1.07-6.77], p < 0.05), an orphan designation (AOR: 3.32, 95%CI [1.38-8.00], p < 0.01), be under priority review (AOR: 2.60, 95%CI [1.17-5.78], p < 0.05), and be monotherapies (AOR: 5.91, 95%CI [1.14-30.65], p < 0.05) than supplementary indications. Initial indications' pivotal trials tended to be shorter (AOR per month: 0.96, 95%CI [0.93-0.99], p < 0.05), of lower phase design (AOR per clinical phase: 0.28, 95%CI [0.09-0.85], p < 0.05), and enroll more patients (AOR per 100 patients: 1.19, 95%CI [1.01-1.39], p < 0.05). CONCLUSIONS: Targeted cancer drugs are increasingly approved for multiple indications of varying clinical benefit. Drugs are first approved as monotherapies in rare diseases with a high unmet need. Whilst expedited regulatory review incentivizes this prioritization, indication-specific safety, efficacy, and pricing policies are necessary to reflect each indication's differential clinical and economic value. SN - 1573-0646 UR - https://neuro.unboundmedicine.com/medline/citation/35389145/Initial_and_supplementary_indication_approval_of_new_targeted_cancer_drugs_by_the_FDA_EMA_Health_Canada_and_TGA_ DB - PRIME DP - Unbound Medicine ER -