Update: Unadjusted relative reductions in the annual rate of FVC decline for the nintedanib studies were added to the story below.
SAN DIEGO (TheStreet) -- Before I dive into the comparison of InterMune's (ITMN) pirfenidone with Boehringer Ingelheim's nintedanib, Dr. Gary Hunninghake, a specialist in idiopathic pulmonary fibrosis (IPF) at Brigham and Women's Hospital in Boston, says declaring one drug better than the other is a fool's errand.
"You cannot tell from the data published," said Hunninghake, referring to the results from three phase III studies (one from InterMune, two from Boehringer) published Sunday in the New England Journal of Medicine. "Both drugs were evaluated in [IPF] patients with relatively early state disease and both had fundamentally similar outcomes."
I spoke with Hunninghake on Thursday. His editorial on the pirfenidone and nintedanib data, titled "A New Hope for Idiopathic Pulmonary Fibrosis," was also published today in the NEJM. He called the new IPF drugs a game changer and says both are likely to be approved in the U.S. Doctors and their IPF patients here will finally have effective therapies to treat a progressive, lung-scarring disease that has a death rate worse than that of many cancers.But Dr. Hunninghake, which company -- InterMune or Boehringer -- has the superior IPF drug? "If either company tries to make a claim that their drug is superior over the other, I would say these data do not support it," he says. With all due respect to Dr. Hunninghake, nothing will stop investors from comparing the pirfenidone and nintedanib study results, so let's get at it. In addition to the NEJM publication today, the pirfenidone and nintedanib data are being highlighted at a press briefing sponsored by the American Thoracic Society (ATS). The data will also be presented at the ATS annual meeting on Tuesday. I previewed these data on Friday. Boehringer conducted two phase III studies of nintedanib dubbed "INPULSIS-1" and "INPULSIS-2." The studies enrolled 513 and 548 IPF patients, respectively. The studies' primary endpoint measured the annual rate of decline in forced vital capacity over 52 weeks for patients treated with netedanib and placebo. In INPULSIS-1, the annual rate of decline in FVC was -114.7 ml for nintedanib versus -239.9 ml for placebo -- a relative reduction of 52% and statistically significant. Unadjusted, the relative reduction was 55%. Here's what the result looks like graphically (from the NEJM):
In INPULSIS-2, the annual rate of decline in FVC was -113.6 ml for nintedanib versus -207.3 ml for placebo -- a relative reduction of 45% and statistically significant. Unadjusted relative reduction: 48%. Here's what that result looks like graphically (again from the NEJM):
In my preview of the IPF data Friday, I mentioned the primary endpoints of the respective phase III studies designed by InterMune and Boehringer were different. InterMune, however, re-analyzed the pirfenidone study using Boehringer's annual rate of FVC decline endpoint. In InterMune's ASCEND phase III study, the annual rate of decline in FVC was -122 ml in the pirfenidone group and -262 ml in the placebo group -- a relative difference of 53% and statistically significant. Here's what this results looks like graphically:
When using Boehringer's primary efficacy endpoint for IPF benefit, InterMune's pirfenidone comes out looking equivalent to nintedanib in one study and superior in the second. [With the caveat that we're comparing across trials.] The primary endpoint of InterMune's ASCEND study measured the proportion of patients in the pirfenidone and placebo arms experiencing a clinically meaningful change (10% or greater) in FVC. The study enrolled 555 IPF patients and achieved its primary endpoint with a high level of statistical significance. At 52 weeks, 16.5% of the IPF patients treated with pirfenidone experienced an FVC decline of 10% or more or death compared to 31.8% in the placebo group. The relative reduction favoring pirfenidone was 48% Boehringer analyzed the nintedanib data from INPULSIS studies to also come up with a categorical description of the drug's efficacy. In INPULSIS-1, 29% of nintedanib-treated patients experienced an FVC decline of 10% or more compared to 43% in the placebo group -- a relative reduction of 33%. In INPULSIS-2, 30% of nintedanib-treated patients experienced an FVC decline of 10% or more compared to 35.5% in the placebo group -- a relative reduction of 15.5%. Using a categorical definition of efficacy in IPF (InterMune's primary endpoint) and comparing across trials, pirfenidone outperformed nintedanib. [Note: InterMune's study enrolled slightly "sicker" IPF patients with a baseline predicted FVC of 67-68% compared to 79-80% in Boehringer's INPULSIS studies.] Let's compare mortality data in the InterMune and Boehringer studies.