This story reports on two trials that showed adding adding one of two new drugs to standard therapy possibly improved short-term lung function in cystic fibrosis patients who fall into two common categories of gene mutations.
The story wisely included the high cost of some of these compounds, known as CFTR (cystic fibrosis transmembrane conductance regulator) modulators. However, the story did not give enough data to help readers make sense of the scope of the benefits. And while it did contain some caveats about the quality of evidence, those cautions were drowned out by numerous optimistic–and speculative–statements about how the drug will perform in future trials.
Cystic fibrosis is genetic disease affecting about 80,000 people worldwide that leads to early death due to progressive lung disease. In recent years CFTR modulators have been developed to target the mutations themselves by correcting the malfunctioning CFTR protein, which regulates the flow of water and chloride in and out of cells lining the lungs and other organs.
But there are many types of mutations that cause cystic fibrosis, and medications developed thus far have been effective only with certain ones.
More widely effective CFTR modulators could greatly improve and dramatically extend the lives of people with cystic fibrosis. But that remains to be seen. As a result, journalists need to proceed very carefully in reporting about studies that test a small number of patients, measure a limited number of outcomes, and cover a short treatment period–especially when these drugs cost could more than a quarter of a million dollars per year.
The story brought up the “real-world issue of price” if the drugs are approved. It reported that the company that makes them — Vertex Pharmaceuticals — markets the combination of two other CFTR modulators — tezacaftor and ivacaftor — for a list price of $292,000 a year.
Additional cost comes from the continued need for hospitalization on a regular basis, at least for some patients. Treating these patients may well cost millions over the course of a decade.
The story said the patients’ performance on a pulmonary function test called FEV1 rose by “as much as 13 percentage points, on average.” That’s not enough information. What was the average starting number? And how did the control groups do in comparison? We’re not told.
Also, FEV1 is a surrogate marker and we don’t know how it translates into real-world benefits on infection rates, hospitalizations, quality of life and lifespan. That should have been pointed out.
The story reported: “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.”
The story should also have said that three patients in the VX-445 trial discontinued treatment, due to severe adverse events including intestinal blockages intestines and temporary worsening of lung function. Another three had to temporarily stop treatment due to signs of liver damage, muscle weakness and constipation. Considering the small size of the trial overall, these numbers are important.
This was a tough call, but on balance we believe the story didn’t sufficiently caution readers about the quality of evidence.
On the plus side, it described the findings as “preliminary” and the trial as “short-term,” lasting four weeks. It mentioned outstanding questions such as whether the improved lung function can be sustained over longer periods, and whether the therapy can achieve other meaningful outcomes such as reducing episodes of diminished lung function or helping with weight gain.
It also quoted researcher Steven Rowe, MD, saying these drugs are “not a cure” and that important questions remain, including how well they work for younger patients.
But those cautions might easily be overlooked due to the prominent hype. That included quoted phrases such as “game-changing” and “breakthrough,” as well as researchers expressing speculative optimism that the results “will hold up” in larger, longer-term trials.
In addition, we think that the small size of these trials should have been emphasized. It’s a stretch to conclude a four-week study of just 239 patients, not all of whom received the therapies being tested, amounts to a breakthrough that will help nearly every cystic fibrosis patient.
The story didn’t engage in disease-mongering. It said more than 30,000 people have cystic fibrosis in the U.S., and most have the genetic mutations targeted by these compounds. We also appreciated the genetic descriptions.
The story reported that Vertex Pharmaceuticals, Inc. is developing both experimental drugs. However, it didn’t report the full extent of the conflicts of interest involved in these trials. A majority of the study authors — including one quoted in the story, Steven Rose, MD — reported receiving grants, personal fees, and other compensation from Vertex Pharmaceuticals during the trial period, according to disclosures filed with the journal. In addition, one of the authors is a Vertex employee who holds a relevant patent.
In addition, we think that the story would have benefited greatly from more independent sources to weigh in on the bold claims being made.
The story mentions existing therapies to target the genetic mutations of cystic fibrosis patients. There are other approaches under study such as such gene editing and stem cell replacement, but those have a ways to go scientifically.
It’s clear that these drugs are not on the market.
The story gives a little bit of background on the other drugs, and how the drugs in this trial are novel.
The story did not appear to rely on a news release.