Abstract
Clinical evidence and benefit of special FDA designations in anti-cancer drugs.
Author
person
Daniel Tobias Michaeli
DKFZ-Hector Cancer Institute and Department of Personalized Oncology, University Medical Center Mannheim; Division of Personalized Medical Oncology, German Cancer Research Center (DKFZ); German Center for Lung Research (DZL), Mannheim, Germany
info_outline
Daniel Tobias Michaeli, Julia Caroline Michaeli, Sebastian Albers, Tobias Boch, Boris Winterhoff, Thomas Michaeli
Full text
Authors
person
Daniel Tobias Michaeli
DKFZ-Hector Cancer Institute and Department of Personalized Oncology, University Medical Center Mannheim; Division of Personalized Medical Oncology, German Cancer Research Center (DKFZ); German Center for Lung Research (DZL), Mannheim, Germany
info_outline
Daniel Tobias Michaeli, Julia Caroline Michaeli, Sebastian Albers, Tobias Boch, Boris Winterhoff, Thomas Michaeli
Organizations
DKFZ-Hector Cancer Institute and Department of Personalized Oncology, University Medical Center Mannheim; Division of Personalized Medical Oncology, German Cancer Research Center (DKFZ); German Center for Lung Research (DZL), Mannheim, Germany, University of Minnesota, Division of Gynecologic Oncology, Minneapolis, MN
Abstract Disclosures
Research Funding
No funding received
None.
Background:
Over the past decades, US congress enabled the US Food and Drug Administration (FDA) to facilitate and expedite drug development for serious conditions filling unmet medical needs with five special designations: orphan, fast track, accelerated approval, priority review, and breakthrough therapy. It remains unclear whether multiple designations per indication are redundant. This study analyzes cancer drugs with multiple special designations regarding their FDA approval timelines, evidence, benefit, epidemiology and price.
Methods:
All anti-cancer drugs and their supplemental indication approvals were identified in the Drugs@FDA database from 2000 to 2022. For each indication, clinical trial characteristics, epidemiologic, and price data were collected from FDA labels, the Global Burden of Disease Study, and Medicare & Medicaid Part B and D, respectively. The association between overall survival (OS) and progression-free survival (PFS) hazard ratios (HR) and drug indications’ number of special designations were compared in meta-analyses and meta-regressions.
Results:
We identified 170 anti-cancer drugs with FDA approval in 455 indications. The median time to first FDA approval was 13.8 years for drugs with zero, 7.3 years with one, 7.1 years with two, 7.8 with three, 5.8 with four, and 5.3 with five special designations (HR per additional designation: 1.27, 95%CI: 1.09-1.48, p=.002). Drug indications with more special designations were more frequently granted to rare diseases with fewer treatment options supported by smaller and shorter open-label phase 1/2 trials. OS HRs were 0.79 for indications with zero, 0.74 with one, 0.73 with two, 0.69 with three, 0.59 with four, and 0.52 with five special designations (p=.024). On average, each additional special designation was associated with lower HRs for OS (ß=-0.03, p=.002) and PFS (ß=-0.07, p<.001). Each additional special designation was associated with a 19.05% (95%CI: 4.56-35.55, p=.013) higher drug price.
Conclusions:
The FDA’s special designations are non-redundant. Multiple special designations are associated with faster approval times and a greater efficacy for patients with high unmet needs, while multiple special designations are associated with less robust trial evidence and higher drug prices. This study supports the strategy of special FDA designations for unmet clinical needs.
7 organizations
1 drug
12 targets
Organization
University Medical Center MannheimOrganization
Division of Personalized Medical OncologyOrganization
German Cancer Research Center (DKFZ)Organization
German Center for Lung Research (DZL)Target
MNK1Target
MannheimTarget
GermanyTarget
University of MinnesotaTarget
Minneapolis