It included patients with a single copy of the most common genetic mutation for the disease.
Results of the international phase 3 clinical trial led the U.S. Food and Drug Administration to approve the therapy last month. The findings were published Oct. 31 in the New England Journal of Medicine.
"This should be a major cause for celebration," Dr. Francis Collins, director of the U.S. National Institutes of Health, wrote in an editorial accompanying the new study.
Cystic fibrosis (CF) is a progressive genetic disease that causes thick mucus to build up in the lungs, digestive tract and other parts of the body, resulting in severe respiratory and digestive problems and other complications such as infections and diabetes.
"Although there are over a thousand different disease-causing mutations, nearly 90% of people with cystic fibrosis have at least one copy of the most common mutation, the Phe508del CFTR allele," said study corresponding author Dr. Raksha Jain. She's the director of the Adult Cystic Fibrosis Center at the University of Texas Southwestern Medical Center in Dallas.
About 80,000 people worldwide have mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, according to Jain. People inherit a gene from each parent that encodes the CFTR protein.
"This three-drug combination was highly effective in people with cystic fibrosis who inherited the Phe508del CFTR mutation, improving health outcomes and symptoms," Jain said in a university news release.
The study, conducted at 115 sites in 13 countries, included 403 patients with one mutated copy of the gene.
Patients were randomly selected to receive either the elexacaftor-tezacaftor-ivacaftor combo (Trikafta) or a placebo. The trial was co-sponsored by Vertex Pharmaceuticals, which makes the drug combo. Its list price is $311,500 a year.
Patients' lung function was assessed at four and 24 weeks. Compared to those in the placebo group, patients who took Trikafta had significantly improved lung function at both checkups.
Symptom flare-ups were 63% lower in the Trikafta group, and these patients also had better questionnaire scores on quality of life and respiratory symptoms than the placebo group, according to the study.
Excessive amounts of salt in sweat is a hallmark of cystic fibrosis. People in the Trikafta group had a lower concentration of salt in their sweat than those in the placebo group, which suggests that the therapy targets the disease's underlying cause, Jain said.
For his part, Collins said that enthusiasm over the study's results should be tempered by the knowledge that 10% of patients won't be helped by this therapy.
"We must not abandon the patients with cystic fibrosis who … will not have a response to these drugs," he wrote. "The 'best day ever' for all of us traveling down this long road together will be the day when the more than 70,000 persons with cystic fibrosis worldwide do not need to take drug therapy at all and there finally is a permanent cure for cystic fibrosis that works for everyone."
And 1% of the Trikafta group stopped taking the drugs due to adverse events, the study authors noted. Further research is needed to learn more about potential side effects, Jain said.
She was also involved in a study that assessed Trikafta on patients with one or two copies of the Phe508del CFTR allele. That study was recently published in The Lancet medical journal.
Jain is presenting results of both studies this week at the North American Cystic Fibrosis Conference, in Nashville, Tenn.
"The CF community is working hard to find highly effective therapies for people who are not eligible for this treatment because they don't have the appropriate gene mutation," she said.
Sources: University of Texas Southwestern Medical Center, news release, Oct. 31, 2019; New England Journal of Medicine, Oct. 31 2019.
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