Vertex Pharmaceuticals will be using its priority review voucher with the US Food and Drug Administration (FDA) with hopes of securing a fast-track approval of its once-daily vanza triple therapy following a successful Phase III programme in cystic fibrosis (CF).

The company has announced that three pivotal trials of the vanza triple met their primary and key secondary endpoints, with plans to submit for regulatory approval globally by mid-2024.

Vanzacaftor / tezacaftor / deutivacaftor is a triple CF transmembrane conductance regulator (CFTR) modulator comprising two correctors and one potentiator which has been investigated in CF patients with one f508del mutation.

The Phase III programme included two randomised, double-blind, active-controlled, 52-week trials, SKYLINE 102 and SKYLINE 103, evaluating the efficacy of vanzacaftor (20mg) / tezacaftor (100mg) / deutivacaftor (250mg) once daily in people with CF aged 12 years and older compared to Trikafta (elexacaftor / tezacaftor / ivacaftor and ivacaftor).

A third Phase III single-arm, 24‑week, open-label study, RIDGELINE 105, evaluated the safety and efficacy of the vanza triple in children with CF aged six to 11 years.

Superior to Trikafta in sweat chloride

Vertex reports that in both SKYLINE 102 and SKYLINE 103, the primary endpoint of absolute change from baseline in per cent predicted forced expiratory volume in one second (ppFEV1) through week 24 was met and showed that treatment with vanza triple was non-inferior to treatment with TRIKAFTA.

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By GlobalData

On the first key secondary endpoint, the vanza triple was superior in reducing sweat chloride (SwCl) levels. In SKYLINE 102, SwCl levels decreased by 7.5 millimoles per litre (mmol/l) for the vanza triple, compared to an increase of 0.9mmol/L for Trikafta. In SKYLINE 103, SwCl levels decreased by 5.1mmol/l for the vanza triple, compared to a reduction of 2.3mmol/l for Trikafta.

The RIDGELINE 105 study met its primary endpoint of safety. On the secondary endpoint of absolute change in SwCl levels, the vanza triple reduced SwCl by -8.6mmol/l with 95% of children achieving SwCl levels below 60mmol/L and the majority of children treated achieving normal levels of CFTR function with SwCl levels below 30mmol/l.

The safety profile remains consistent with Trkafta and was well tolerated in all three studies.

Cystic fibrosis landscape

Vertex has a large grasp on the CF market, with sales of its flagship CFTR modulator Trikafta reaching $8.9bn in 2023.

GlobalData predicts that sales of the new triple will hit $4.1bn in 2029, however, in the same year Trikafta sales are predicted to hit $10.8bn.

GlobalData is the parent company of the Clinical Trials Arena.

CFTR modulators only benefit around 85% of CF patients, leaving a big gap in the market for treatments addressing the remaining 15%. Vertex aims to get a grasp on this and develop an mRNA therapy alongside Moderna for this patient group, although other companies are also trialling similar candidates.

There are also ongoing trials of gene therapies for CF that would provide long-lasting or potentially permanent treatment.