Treatment with 3 drugs could be a breakthrough in cystic fibrosis

The Rowe team has tested a combination of two available CFTR modulators – tezakaftor and ivakaftor – and an experimental one, called VX-659. The other trial was using the same existing drugs, as well as a new, similar drug called VX-445.

The Rowe team randomly assigned 54 adults with cystic fibrosis to follow the three-drug regimen or to be part of a control group. In the comparison group, patients with a F508del mutation took a placebo, while patients with two copies of the mutation took tezakaftor and ivakaftor alone.

The trial showed that triple therapy improved lung function in patients with both types of mutations after four weeks. Their performance in a test called FEV1 increased by 13 percentage points on average – what Rowe described as a "steep improvement".

The other test had almost identical results.

It's the first time, says Rowe, that CFTR modulator treatment "pushes the needle" in patients with a F508del mutation.

An editorial published with the studies indicates that they "represent a major breakthrough".

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

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

"The ability of these potential drugs to treat individuals carrying a single F508del mutation means that more people than ever before could benefit," said Dr. Michael Boyle, executive vice president of therapeutic products at the foundation. "It's a very exciting news for our community."

Rowe agreed that there remained important questions about three-drug regimens. The first is, how do they work for younger patients?

Patients younger than 12 years old are included in the larger trials underway, Rowe said.

Until now, the treatments seem safe. Most of the side effects seen in clinical trials lasting four weeks were "mild to moderate," the researchers said.

If the experimental drugs are finally approved, there will be a real world price problem.

Vertex currently markets the combination of tezakaftor and ivakaftor under the name Symdeko – at a list price of $ 292,000 per year.

In the United States, more than 30,000 people have cystic fibrosis, according to the foundation.