In what researchers call a "breakthrough", two preliminary studies have shown that one of two triple medicine regimens can potentially…
In what researchers call a “breakthrough”, two preliminary studies have shown that one of two triple medicine regimens can potentially benefit 90 percent of people with cystic fibrosis.
The samples were short-term and found that drug combinations improved adult patient lung function over four weeks. But experts said they were optimistic. The results will depend on the larger, longer thermal trials already in progress.
What is most exciting, they say, that the triple drug method could open up new options for almost all patients with cystic fibrosis.
“This is not a cure for cystic fibrosis,” stressed Dr. Steven Rowe, who led one of the trials. “But it can be game change.”
Cystic fibrosis (CF) is a genetic disorder that causes persistent pulmonary infections. Over time, extensive lung damage leads to breathing failure. At one time, children with CF usually died before reaching school age. But with improved treatments, the typical lifespan is now about 40 years, according to the Cystic Fibrosis Foundation.
Cystic fibrosis is caused by different mutations in a gene called CFTR. In recent years, drugs that target the underlying genetics have become available. Known as CFTR modulators, they were derived as an important advancement in the treatment of the disease.
However, they only work well for a small number of people with certain CFTR mutations, explained Rowe, director of the Cystic Fibrosis Research Center at the University of Alabama, Birmingham.
The most common mutation that causes cystic fibrosis is called F508del ̵
1; and it has proved tougher to deal with, Rowe said.
About half of people with CF carry two copies of the mutation (one hereditary inheritance). For them, a combination of two existing CFTR modulators can ease breathing difficulties – but the overall effects are just “modest,” says Rowe.
Then there are 30 percent of CF patients who only carry a copy of F508del plus another defect known as a “minimal-function” mutation. For them, the existing CFTR modulators do not work at all.
Both new trials focused on the two patient groups. The results were recently published in the New England Journal of Medicine, which coincided with the researchers’ presentation at a North American Cystic Fibrosis Meeting in Denver.
Rowes team tested a combination of two available CFTR modulators – tezakaftor and ivakaftor – plus an experimental, called VX-659. The second attempt used the same existing drug, along with a similar new drug called VX-445.
Rowes team randomly assigned 54 adults with cystic fibrosis to either take the triple drug regimen or be in a comparison group. In the comparison group, patients with F508del mutation took placebo pills, while patients with two copies of the mutation took tezacaft and ivakaftor alone.
After four weeks, the trials of triple drug therapy showed improved lung function in patients with both types of mutations. Their performance on a test called FEV1 increased by as much as 13 percentage points, on average – what Rowe described as a “pronounced improvement.”
The second attempt had almost identical results.
This is the first time, Rowe said CFTR modulator therapy has “pushed the needle” for patients with a F508del mutation.
An editorial published with the studies said that they “constitute a major breakthrough.”
Now the question is whether the improved lung function can last and if the drugs prevent symptoms and other complications, Dr. Fernando Holguin of the University of Colorado, Aurora.
The Cystic Fibrosis Foundation helped fund work through a contribution to Vertex Pharmaceuticals, Inc., which develops both experimental drugs.
“The ability of these potential drugs to treat individuals with a single F508del mutation means that more than ever before can benefit,” says Dr. Michael Boyle, senior vice president of therapy at the ground. “This is very exciting news for our society.”
Rowe agreed that there are still important questions about triple medicine regimes. One is, how well do they work for younger patients?
Patients as young as 12 are included in the major ongoing trials, said Rowe.
So far the treatments are sure to be safe. Most adverse events in four weeks’ attempts were “mild to moderate,” said the researchers, including cough, headache and increased sputum.
Finally, if the experimental drugs are approved, it will be the real issue of price
Vertex currently markets the combination of tezakaftor and ivakaftor as Symdeko – at a reported list price of $ 292,000 a year.
In the United States, more than 30,000 people have cystic fibrosis.
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