Differential times of submission and approval of CFTR modulators for the treatment of Cystic Fibrosis in the United States and the European Union.

Background: The objective of this study was to assess the differential times of submission and approval of CFTR modulators in the United States (US) and the European Union (EU).
Methods: By collecting publicly available data from the websites of the Food and Drug Administration and the European Medicines Agency, we quantified differential times in submission, review duration, and approvals of initial marketing authorization and variation of indications of CFTR modulators in the US and the EU by December 31, 2023.
Results: Applications regarding marketing of 4 CFTR modulators were submitted 103 (SD ±143) days later in the EU than in the US: 31 (SD ±39) days later for initial approval, and 124 (SD ±155) days for supplemental indications. The regulatory review process was completed in 181 days [IQR, 179 - 182] in the US and 325 days [IQR, 276 - 382] in the EU: 167 days [IQR, 102 - 232] in the US and 346 days [IQR, 302 - 400] in the EU for first approvals, 181 days [IQR, 181 - 182] in the US and 324 days [IQR, 264 - 382] in the EU for supplemental indication approvals. CFTR modulators were approved 267 (SD 143) days later in the EU than in the US: 220 (SD ±76) days for initial approval and 280 (SD ±157) days for supplemental indications.
Conclusion: We found significant differences in times of submission and for approval of CFTR modulators between the US and EU, whereby initial approvals and subsequent indication approvals were always first granted in the US.
Competing Interests: Declaration of competing interest Enrico Costa - Member of the Committee for Orphan Medicinal Products (COMP) at the EMA. The views expressed in this article are personal views and may not be understood or quoted as being made on behalf of or reflecting the position of the EMA. Silvia Girotti - None. Clément Mathieu - None. Carlo Castellani – Dr. Castellani has received payment or honoraria for lectures, presentations, speakers or educational events from Vertex Pharmaaceuticals and Chiesi, and he has participated on a Data Safety Monitoring Board or Advisory Board of Vertex Pharmaaceuticals and Chiesi. Joseph S. Ross - Dr. Ross currently receives research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing, from the Food and Drug Administration for the Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation (CERSI) program (U01FD005938), from the Agency for Healthcare Research and Quality (R01HS022882), and from Arnold Ventures; formerly received research support from the Medical Device Innovation Consortium as part of the National Evaluation System for Health Technology (NEST) and from the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH) (R01HS025164, R01HL144644); and in addition, Dr. Ross was an expert witness at the request of Relator's attorneys, the Greene Law Firm, in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen Inc. that was settled September 2022. Jennifer L. Taylor-Cousar - In the last 36 months, unrelated to this work, she has received grants to her institution from the Cystic Fibrosis Foundation, the National Institutes of Health, Vertex Pharmaceuticals Incorporated, Eloxx, and 4DMT; has received fees from Vertex Pharmaceuticals Incorporated related to consultation on clinical research design and participation on advisory boards; and has provided clinical trial design consultation for 4DMT. She served on a DMC for AbbVie. She serves as the adult patient care representative to the CFF Board of Trustees, and on the CF Foundation's Clinical Research Executive Committee, Clinical Research Advisory Board, and as immediate past chair of the CF TDN's Sexual Health, Reproduction and Gender Research Working Group, on the scientific advisory board for Emily's Entourage, and on the ATS Respiratory Health Awards Committee and is the ICC Chair-elect and served previously on the ATS Scientific Grant Review and Clinical Problems Assembly Programming Committees. She is also a member of the International Advisory Board for Lancet Respiratory Medicine and the Editorial Board for the Journal of Cystic Fibrosis. Hubert G. M. Leufkens - None.
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