Vertex's triple combination therapy Trikafta garners FDA approval for cystic fibrosis five months early

The FDA announced Monday that it has approved Vertex Pharmaceuticals' filing for Trikafta, which combines its next-generation CFTR corrector elexacaftor with the company's Symdeko (ivacaftor/tezacaftor), for cystic fibrosis patients 12 years and older who have at least one F508del mutation in the CFTR gene. The FDA stated that its decision, which was originally expected to come March 19 of next year, marks the first triple combination therapy available for patients with the most common mutation, affecting an estimated 90% of the cystic fibrosis population.

FDA Commissioner Ned Sharpless said the approval makes the treatment "available to most cystic fibrosis patients, including adolescents, who previously had no options." He added that the agency " used all available programmes, including priority review, fast track, breakthrough therapy and orphan drug designations, to help advance today's approval in the most efficient manner possible, while also adhering to our high standards."

The efficacy of Trikafta was demonstrated in two randomised Phase III studies. The first was a 24-week trial involving 403 patients who had an F508del mutation, as well as a mutation on the second allele that results in either no CFTR protein or a CFTR protein that is not responsive to Vertex's other cystic fibrosis drugs, Kalydeco (ivacaftor) or Symdeko alone. The second study lasted four weeks and included 107 patients who had two identical F508del mutations. The primary analysis for each assessed lung disease progression by looking at percent predicted forced expiratory volume in one second (ppFEV1).

Results from the first trial showed that Trikafta increased mean ppFEV1 by 13.8% from baseline versus placebo, and by 10% from baseline compared to Symdeko. The FDA noted that in the first trial, Trikafta also led to improvements in sweat chloride, number of pulmonary exacerbations and body mass index compared to placebo. The drug's safety profile, based on data from the 510 patients enrolled in the two trials, was "generally similar across all subgroups of patients," the agency added.

CEO Jeffrey Leiden remarked that "for approximately 6000 people with cystic fibrosis in the US, Trikafta is the first medicine that can treat the underlying cause of their disease." Vertex has also submitted a marketing application for the triple combination therapy with regulators in the EU. Meanwhile, the treatment is currently in Phase III testing for use in patients ages 6 through 11 years who have one F508del mutation and one minimal function mutation, as well as those with two F508del mutations. The company indicated that it also plans to evaluate the therapy in children under the age of six as part of planned future studies.

For related analysis, see ViewPoints: Vertex settles on a dynastic successor.

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