The U.S. Food and Drug Administration (FDA) has approved Symdeko (tezacaftor/ivacaftor and ivacaftor) tablets for the treatment of children, ages 6 to 11 years, with cystic fibrosis (CF) who have certain mutations that respond to treatment, its developer, Vertex Pharmaceuticals, has announced.
In order to be eligible for the treatment, children must carry either two copies of the F508 deletion — the most common genetic mutation associated with CF — or have at least one mutation in the CFTR gene that responds to treatment with Symdeko.
Symdeko, known as Symkevi in Europe, contains a combination of tezacaftor (VX-661) and ivacaftor (sold by Vertex under the brand name Kalydeco). The combo therapy is meant to restore the activity of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which is impaired in CF patients carrying different genetic mutations in the CFTR gene.
Last year, the FDA approved Symdeko for the treatment of children with CF who are 12 or older and carry certain genetic mutations. In the meantime, the medication has also been approved for the same indication in the E.U., Canada, and Australia.
Now, besides approving the expansion of Symdeko’s original indication to include younger children, the FDA has approved the commercialization of higher dosage Symdeko tablets (tezacaftor 50 mg/ivacaftor 75 mg and ivacaftor 75 mg).
“Today’s expanded approval of Symdeko in children ages 6 through 11 is an important step in our efforts to continue to bring treatment options to the youngest patients possible and importantly brings us closer to our goal of developing medicines for all people living with CF,” Reshma Kewalramani, MD, executive vice president and chief medical officer at Vertex, said in a press release.
The aproval “also provides more context on the safety and dosing specific to this population,” added Banu Karimi-Shah, MD, acting deputy director of the division of pulmonary, allergy, and rheumatology products in the FDA’s Center for Drug Evaluation and Research, in another press release.
The FDA’s decision was largely based on data from a 24-week multicenter, open-label, Phase 3 trial (NCT02953314) that assessed the safety, tolerability, and chemical properties of Symdeko in a group of 70 CF children from 6 to 11 years old in the U.S. and Canada.
The trial’s findings showed that the safety and tolerability profile of Symdeko among the children was similar to that reported in previous Phase 3 trials assessing the effects of Symdeko in children with CF who were 12 or older. The company is planning to publish the full data from the trial later this year.
The efficacy of Symdeko among younger children was mostly extrapolated from findings obtained in children, 12 or older, who participated in three Phase 3, double blind, placebo-controlled trials — EVOLVE (NCT02347657), EXPAND (NCT02392234), and EXTEND (NCT02565914) — with additional support from data obtained in patients between 6 and 12 years old.
In general, treatment with Symdeko led to significant improvements in lung function and to reductions in the frequency of CF exacerbations (episodes in which the symptoms of the disease worsen significantly and require medical treatment).
“We’ve seen the clinical impact of Symdeko in people with CF aged 12 years and above, and this approval marks a crucial milestone for patients ages 6 through 11 years who may benefit from CFTR modulation, enabling us to treat the basic defect in CF at an earlier stage of disease,” said Seth Walker, MD, at University Hospitals of Cleveland, Cleveland Medical Center, Rainbow Babies and Children’s Hospital. “Symdeko is an important treatment option for eligible people with CF who either never started or have discontinued another CFTR modulator.”
Vertex is now planning to submit an application to the European Medicines Agency later this year seeking the extension of Symdeko’s indication to also include children from 6 and 11 years.