Next-in-class combination treatment shows potential in cystic fibrosis

Vertex Pharmaceuticals’ once-daily small molecule vanzacaftor/tezacaftor/deutivacaftor (vanza triple) for cystic fibrosis (CF) has gleaned positive results in Phase III trials.

The Phase III trials

The clinical programme for the once daily vanza triple was comprised of two Phase III trials: SKYLINE 102 and SKYLINE 103, evaluating the efficacy of vanzacaftor (20 mg)/tezacaftor (100 mg)/deutivacaftor (250 mg) in cystic fibrosis patients 12 years and older with at least one F508del mutation or a mutation responsive to triple combination CFTR modulators (CFTRm), compared to TRIKAFTA^® (elexacaftor/tezacaftor/ivacaftor and ivacaftor).

A third Phase III study was also part of the programme. RIDGELINE 105, evaluated the safety and efficacy of the vanza triple in children with cystic fibrosis between six and 11 years old with at least one mutation responsive to triple combination CFTRm.

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Efficacy of the vanzacaftor/tezacaftor/deutivacaftor (vanza triple)

Vertex also shared that in the SKYLINE 102 and SKYLINE 103, head-to-head against TRIKAFTA, for first key secondary endpoint, the vanza triple was found to be superior in reducing sweat chloride (SwCl) levels.

In the Phase III RIDGELINE 105 study, following treatment with the vanza triple, 95 percent of children were observed to have a SwCl level below 60 mmol/L through 24 weeks. Additionally, 53 percent of children had a SwCl level below 30 mmol/L.

“These results were particularly striking in the paediatric study where 95 percent of children achieved a SwCl level below 60 mmol/L, the diagnostic cut-off for a positive test for cystic fibrosis, and more than 50 percent of children achieved a SwCl level below carrier levels where they may see no symptoms of disease at all,” commented Dr Bonnie Ramsey, Professor Emerita of Pediatrics, University of Washington School of Medicine, Senior Consultant to the CF Foundation Therapeutics Development Network and Co-Chair of Vertex’s CFTR Modulator Steering Committee.

Overall, the results demonstrate that “vanza triple is non-inferior to TRIKAFTA in improving lung function and superior to TRIKAFTA in lowering levels of sweat chloride in people living with cystic fibrosis, setting a new standard for the level of CFTR protein function achievable, and raising the very high bar set by TRIKAFTA,” stated Dr Carmen Bozic, Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex Pharmaceuticals.

Treatment with the vanza triple was well tolerated in all three studies.

Regulatory plans for the cystic fibrosis medicine

By mid-2024, Vertex declared that it plans to submit a New Drug Application (NDA) to the US Food and Drug Administration and a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA) in patients with cystic fibrosis aged six years and older.

Vertex confirmed that full data set from these studies will be presented at medical meetings later in 2024.