Vertex to replace Trikafta as gold standard treatment for cystic fibrosis but other CTFR therapies welcome, says GlobalData

Of the five late-stage pipeline products expected to be licensed in the 7MM* for cystic fibrosis (CF) between 2020 and 2030, four will be CF transmembrane conductance regulator (CFTR) modulators, according to GlobalData. The leading data and analytics company notes that Vertex’s next-generation triple combination, VX-121 + tezacaftor + VX-561 (deutivacaftor), is expected to replace Trikafta/Kaftrio as gold standard treatment for CF.

Mandana Emamzadeh, PhD, Healthcare Analyst at GlobalData, comments: “KOLs noted that superior efficacy and less-frequent dosing of Vertex’s VX-121 + tezacaftor + VX-561 (deutivacaftor) will result in rapid uptake, with many patients shifting from Trikafta/Kaftrio, current standard of care. Furthermore, they supported development of more CFTR modulators for patients who develop intolerances or allergies – or indeed experience adverse events in response to established products. Additionally, further competition could help to drive down drug prices, to the benefit of the consumers.”

GlobalData’s latest report, Cystic Fibrosis – Global Drug Forecast and Market Analysis to 2030 has analyzed the upcoming pipeline for CF and identified that there will be five late-stage Phase II products, including two CF transmembrane conductance regulator (CFTR) modulator regimens from Vertex Pharmaceuticals, VX-561 (deutivacaftor) alone and in a triple combination with VX-121 and tezacaftor; two CFTR modulator regimens from AbbVie, ABBV-3067 alone and in combination with galicaftor (ABBV-2222); as well as an anti-inflammatory agent in development by Laurent Pharmaceuticals, LAU-7b (fenretinide).

Emamzadeh takes a closer look at some of these offerings below.


Vertex has completed one Phase II study (NCT03912233) of its next-generation triple combination therapy, VX-121 + tezacaftor + VX-561 (deutivacaftor), in CF patients ages 18 and older that have either one F508del mutation and one minimal function CFTR mutation or two F508del mutations.

The regimen was reported to be well tolerated and achieved the primary goal of improved lung function and the secondary goal of reducing sweat chloride, of which high levels are a hallmark of CF.

Emamzadeh notes: “The VX-121 + tezacaftor + VX-561 program was granted FDA fast track and orphan drug designations, which will facilitate clinical development and expedite regulatory approval. Data from the Phase II dose-ranging study of VX-561 (deutivacaftor) alone are due to report in the near future.”

Two Phase III trials are now being planned to evaluate VX-121 + tezacaftor + VX-561 in CF patients ages 12 years and older. The first study will recruit patients with one F508del mutation and one minimal function mutation, while the second study will recruit patients that carry either two F508del mutations or one F508del mutation and a second mutation responsive to the given CFTR modulators.


AbbVie’s CFTR potentiator ABBV-3067 – administered alone and in combination with CFTR corrector ABBV-2222 – is being studied to target CF patients that are homozygous for the F508del mutation.

Emamzadeh comments: “Since these pipeline agents are not expected to treat new mutations – or greatly improve efficacy and safety – GlobalData believes these me-too drugs will mainly serve as alternatives to currently marketed CFTR modulator drugs. Although AbbVie is a global biopharmaceutical company and can support the development and potential commercialization of these pipeline drugs across the 7MM, GlobalData expects ABBV-3067 and ABBV-3067 + ABBV-2222 will face strong competition from Vertex’s well-established repertoire of marketed CFTR modulators.”

Laurent Pharmaceuticals

Laurent Pharmaceuticals’ LAU-7b (fenretinide), if successful,  is expected to be the first approved anti-inflammatory agent for CF. The ongoing late-stage Phase II APPLAUD trial (NCT03265288) is evaluating the safety and efficacy of LAU-7b for the treatment of CF patients ages 18 years and older.

Emamzadeh comments: “KOLs believed that the treatment paradigm is certainly missing a CF-specific anti-inflammatory drug. However, prospects for this drug remain uncertain. Firstly, LAU-7b’s manufacturer is a private company with limited experience in product development and commercialization. In addition, the drug would need to compete with other anti-inflammatory drugs recommended by guidelines including azithromycin, ibuprofen, and prednisolone, all with a well-established reputation, commercially and clinically and lower cost. Finally, no data regarding LAU-7b’s efficacy and safety have yet been made available, although Phase II completion is expected in Q3 2021.”

*7MM = US, France, Germany, Italy, Spain, UK, and Canada

More Media