Cystic fibrosis (CF) is the most common genetic disease among individuals of European descent. The introduction of CF transmembrane conductance regulator (CFTR) modulators to the market yielded a shift in research and development (R&D) towards therapies that target the disease’s underlying cause. While Vertex has a monopoly on the CFTR modulator market, its Trikafta/Kaftrio (elexacaftor + tezacaftor + ivacaftor and ivacaftor) has greatly expanded the number of CF-related mutations eligible for CFTR modulator treatment across age groups. In November last year, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended the expanded approval of Kaftrio for children aged 6–11 years with CF. Following that recommendation, the drug was approved for this age group on 11 January this year.

Trikafta/Kaftrio is a next-generation, triple-combination therapy consisting of a CFTR potentiator and two CFTR correctors, namely tezacaftor and elexacaftor. In the US, Trikafta was first approved for patients aged 12 years and older in October 2019. Last June, the drug received approval for patients aged 6–11 years who have two copies of the CFTR gene, at least one F508del mutation in the CFTR gene, or a mutation in the CFTR gene that is responsive to Trikafta based on in vitro data. In Europe and Canada, Trikafta/Kaftrio was first approved in August 2020 and last June respectively for CF patients aged 12 years and older. Canada lags behind other markets, however, in terms of CFTR modulator approval and reimbursement. In October last year, Vertex’s Supplement to a New Drug Submission (SANDS) for Trikafta in patients aged 6–11 years was accepted for Priority Review by Health Canada. If successful, a Health Canada approval will mark the availability of Trikafta/Kaftrio for CF patients aged six years and older across the seven major pharmaceutical markets (7MM), namely the US, France, Italy, Germany, Spain, the UK and Canada.

Following its launch, Trikafta/Kaftrio was reported to reduce the use of symptomatic drug classes such as antibiotics, mucolytics and anti-inflammatory drugs due to overall improvements to patient lung health. As a result, children with CF born today have a more optimistic prognosis than those born more than 30 years ago. The overall survival of CF patients has increased remarkably over the past few decades, and the majority of CF patients in the US and UK are now expected to live beyond their late 40s due to Trikafta/Kaftrio’s impacts on improving lung health. According to the Cystic Fibrosis Foundation (CFF) and Cystic Fibrosis Trust (CFT), most CF patients reach adulthood with currently available treatments. Key opinion leaders interviewed by GlobalData asserted that for patients born in the past decade, the median survival is more than 50 years of age.

At present, Trikafta/Kaftrio is the world’s first triple-combination CF therapy, with around 90% of the CF population likely to be eligible for it. In addition, Vertex Pharmaceuticals is investigating Trikafta/Kaftrio in Phase III (NCT04537793) for CF patients aged two to five years to expand the label for its game-changer drug in the 7MM. If successful, Trikafta/Kaftrio will be available for the majority of CF-related mutations across all age groups. GlobalData estimated that Trikafta’s global peak sales will reach $7.2bn in 2024, after which sales will decline due to competition from other CFTR modulators.

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