OBJECTIVES: To track the orphan drug status, marketing authorization and market access of drug products in cystic fibrosis (CF), a rare, inherited, and life-threatening disorder that requires treatment to improve patients’ quality of life.

METHODS: Data on the orphan drug status and regulatory drug approvals for nine drugs were collected from 1994 to May 2019 from the Food and Drug Administration (FDA), European Medicines Agency (EMA), Health Canada (HC), and Therapeutic Goods Administration (TGA) websites. Health technology assessments (HTAs) for six drugs from CADTH (Canada), G-BA and IQWiG (Germany), HAS (France), NICE (UK), PBAC (Australia), SMC (Scotland), and TLV (Sweden) were evaluated.

RESULTS:

Regulatory Approval: The first drug to treat CF was approved in 1994. It improved lung function and reduced the risk of respiratory infections but did not treat the underlying disease. The first disease-modifying drug, ivacaftor, was approved in 2012 whereas lumacaftor-ivacaftor, tezacaftor-ivacaftor, and tezacaftor-ivacaftor + ivacaftor were approved in the next several years.

Market Access: The base-case incremental cost-effectiveness ratio (ICER) of £310,879 (lumacaftor-ivacaftor), £473,071 (ivacaftor), or > $200,000 (aztreonam) per quality-adjusted life year (QALY) resulted in Do not recommend decisions. Current market access shows that G-BA (n = 2/2), HAS (n = 4/5), and TLV (n = 4/4) recommend more drugs without restrictions for the treatment of CF than CADTH (n = 0/6), NICE (n = 0/2), PBAC (n = 0/5), and SMC (n = 1/5). CADTH, NICE, PBAC, and SMC tend to apply restrictions or give Do not recommend decisions mainly due to uncertain efficacy/effectiveness or uncertain/low cost-effectiveness.

CONCLUSIONS: High base-case ICER, high cost, uncertain or lower cost-effectiveness, and/or uncertain efficacy/effectiveness are obstacles in the path to gaining market access for CF therapies, even when the drugs treat the underlying disease.