3-Drug Therapy Might Be Cystic Fibrosis Advance

Rowe’s team tested a combination of two available CFTR modulators — tezakaftor and ivakaftor — plus an experimental one, known as VX-659. The other trial used the same existing drugs, along with a similar new drug, dubbed VX-445.

Rowe’s team randomly badigned 54 adults with cystic fibrosis to either take the triple-drug regimen or be in a comparison group. In the comparison group, patients with one F508del mutation took placebo pills, while patients with two copies of the mutation took tezakaftor and ivakaftor alone.

After four weeks, the trial found, the triple-drug therapy had improved lung function in patients with both types of mutations. Their performance on a test called FEV1 rose by as much as 13 percentage points, on average — what Rowe described as a “pronounced improvement.”

The other trial had nearly identical results.

This is the first time, Rowe said, that CFTR modulator therapy has “pushed the needle” for patients with one F508del mutation.

An editorial published with the studies said they “represent a major breakthrough.”

Now the questions are whether the improved lung function can be sustained, and whether the drugs prevent symptom exacerbations and other complications, wrote Dr. Fernando Holguin, of the University of Colorado, Aurora.

The Cystic Fibrosis Foundation helped fund the work through a grant to Vertex Pharmaceuticals, Inc., which is developing both experimental drugs.

“The ability of these potential drugs to treat individuals with a single F508del mutation means that more people than ever before could benefit,” said Dr. Michael Boyle, senior vice president for therapeutics at the foundation. “This is very exciting news for our community.”

Rowe agreed there are still important questions about the triple-drug regimens. One is, how well do they work for younger patients?

Patients as young as 12 are included in the larger ongoing trials, Rowe said.

So far, the treatments appear safe. Most side effects in the four-week trials were “mild to moderate,” the researchers said, and included cough, headache and increased sputum.

If the experimental drugs are ultimately approved, there will be the real-world 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, according to the foundation.