An adequate summary of this asthma drug trial’s design doesn’t make up for the overly optimistic tone about the drug’s future. A New York Times story was better.
The story provides just about everything you would need to know to decide that this small, short trial had too many problems to prove much of anything. But the story’s reference to this as a “potential game changer,” coupled with quotes from the researchers that are so effusive, and the numbers used to back up the researchers claims are — on the surface — so striking, that most readers will leave this story with the mistaken impression that an massive advance in asthma treatment is just around the corner.
The vast majority of people with asthma can control their symptoms with a combination of inhaled corticosteroids and long acting beta agonist drugs. Unfortunately, there is a small population of people whose asthma proves to be more resistant. Drugs targeting specific proteins that are involved in inflammation, such as the interleukins are under development in many companies. While there have been positive signs, not all drugs that have shown promise in early stage testing have proven to be useful in later stages of development. The early results with dupilmumab are encouraging but the road to FDA approval is not easy or straightforward. Reports of early stage studies in small and very select groups of subjects need to be viewed cautiously. “Potential game changer” language sounds more like cheerleading than independent vetting.
There is no cost information in the story.
The cost of existing monoclonal antibodies used to treat rheumatoid arthritis and other diseases can be in the thousand of dollars per month with many insurance companies either restricting access or requiring large patient co-pays.
The story starts out by providing what appears to a quantification of the benefits of the drug saying that the “asthma drug meant to attack the underlying causes of the respiratory disease slashed episodes by 87 percent,” and it goes on to quickly provide some much needed context by saying that the drug was studied in a trial involving 104 patients. It takes quite a while for the story to explain where that 87% number came from, and the explanation itself is a little unsatisfactory. It says, “’By end of the trial, after 12 weeks, 44 percent of those in the placebo group had exacerbations, compared with 5 percent of those on dupilumab,’ Wenzel said. That represented an 87 percent reduction in exacerbations, which was highly statistically significant.” We don’t doubt that it was statistically significant, but we would have liked to have known how many patients really saw a benefit.
Here’s what the authors said in the paper:
“Asthma exacerbations occurred in 26 patients: 3 receiving dupilumab (6%) and 23 receiving placebo (44%) (odds ratio with dupilumab, 0.08; 95% confidence interval [CI], 0.02 to 0.28; P<0.001).”
The reporter takes it on the lead researcher’s word that the “dupilumab was well tolerated, with side effects similar to placebo. But she cautioned that longer trials are needed to fully assess the drug.” We would have liked to have seen those side effect numbers. Similar to placebo? Does that mean 10 patients in the drug group had side effects and a dozen in the placebo group? Does it mean three and six? Just give us the numbers.
Importantly, one subject receiving dupilumab developed angioedema, a serious and potentially life threatening allergic reaction presumably due to the drug.
And even the accompany editorial in the New England Journal of Medicine drew attention to safety questions:
“Given the appearance of increased eosinophilia in four patients in the dupilumab group, more safety data are also required.”
The story provides enough information for people to get a well rounded picture of the study and its limitations. It didn’t involve very many patients. It was conducted for a short period of time. It may have been confounded by the fact that the patients were taking multiple drugs at the same time. And, most importantly, the story says, “The trial recruited patients with high levels of eosinophils, a biomarker that shows immune system cells called type 2 helper T cells (Th2 cells) associated with allergy and asthma have been activated. Such patients were deemed likely to benefit from treatment.” It returns to this theme by referring to a New England Journal of Medicine editorial that accompanied the drug study. The story says, “But the editorial said effectiveness of dupilumab has been established in just a ‘limited subpopulation of patients with asthma’ because only 21 percent of those screened for enrollment in the study met its criteria.”
Unfortunately, much of that detail is overwhelmed by two references to this being “a potential game changer.”
There is no disease mongering in this story.
There was too much reliance on sources connected to the trial. The very first quote is from the lead researcher, effusing: “Overall, these are the most exciting data we’ve seen in asthma in 20 years,” said Dr. Sally Wenzel, lead investigator for the 104-patient study of dupilumab, an injectable treatment being developed by Regeneron Pharmaceuticals Inc and French drugmaker Sanofi. The only other person quoted is George Yancopoulos, Regeneron’s research chief. At the very end, an anonymous editorial is quoted with some words of caution that most readers won’t even get to.
At one point the story said “researchers expressed optimism.” Which researchers? Those funded to do the study?
The story did not attempt to compare this drug to other drugs or treatments for asthma. (Olamizumab [Xolair], for example, has been available for a number of years to treat severe allergy and asthma.) Instead, it made glancing references to other drugs, always disparagingly. For example, it quotes the lead researcher saying, “We have been treating asthma with sort of Band-Aid therapies that didn’t get at the underlying causes.”
Right in the lead, the story signals that this drug is not currently available, and, to the knowledgeable reader, shows where it is in the regulatory process, referring to a “mid-stage trial.” Later, it also says that “far larger trials will be needed to confirm findings from the “proof of concept” study.”
However, calling this “a potential game changer for patients with moderate to severe disease” may imply a more imminent definitive answer than actually exists.
The relative novelty of this drug, and of the findings, are appropriately described in the story.
This story does not rely on a press release.