Background: The high prices of CFTR modulators present barriers to access for people with cystic fibrosis (pwCF), especially those in low- and middle-income countries. Costs of research and development (R&D) are often cited as key drivers of drug pricing. In the case of CFTR modulators, circumstances allow for a meaningful comparison of pre-marketing R&D spending and post-approval product revenues.

Methods: Data on R&D expenditure and CFTR modulator revenues from Q3 2001 (the initial acquisition of CFTR modulator research) until 2024 were extracted from the originator company’s Securities and Exchange Commission filings. All values were inflation-adjusted to 2024. Cost of capital was incorporated at a discount rate of 10.5%, with rates of 7% and 14% modelled for sensitivity analysis.

Results: Total out-of-pocket R&D expenditure prior to the successful marketing of elexacaftor/tezacaftor/ivacaftor in Q3 2019 was $18.5 billion. Cost of capital was estimated at $24.8 [13.2-41.6] billion. Actual costs associated with CFTR modulators are likely significantly lower than total R&D spending. Cumulative CFTR modulator revenues from 2012-24 were $63.8 billion, surpassing R&D expenditure in Q2 2020. At over $10.2 billion annually, elexacaftor/tezacaftor/ivacaftor represents one of the highest revenue pharmaceutical products currently on the market.

Conclusion: High revenues mean that R&D costs associated with CFTR modulators have been recouped early in their commercial lifespan. However, their pricing threatens global health equity for pwCF and the financial sustainability of health systems. In the eve of genetic therapies in CF and other rare diseases, sustainable solutions balancing equitable access and financial reward are urgently required.