All-cause mortality in the pooled INPULSIS studies was 5.5% in the nintedanib arms versus 7.8% in the placebo arms -- a 30% relative reduction in the risk of death favoring nintedanib but not statistically significant.
The death rate due to respiratory cause was 3.8% in the nintedanib patients compared to 5% in the placebo groups -- a 26% relative reduction in risk of death but again, not statistically significant.
Switching to InterMune's ASCEND study, the rate of all-cause mortality in pirfenidone-treated patients was 4% versus 7.2% in placebo patients -- a 45% relative reduction in the risk of death but not statistically significant.
With FDA's blessing, InterMune pooled survival data from ASCEND with the previous phase III CAPACITY studies. When these studies are combined, the death rate in the pirfenidone arm is 3.5% compared to 6.7% in placebo-treated patients -- a 48% relative reduction in the risk, which is statistically significant.
InterMune can make a legitimate claim to a mortality benefit for pirfenidone in IPF with the pooled data from the ASCEND and CAPACITY trials. How this survival benefit shows up in the pirfenidone label is yet to be determined.
Boehringer says the INPULSIS studies were not powered to demonstrate a nintedanib survival benefit. It's interesting however, that the two INPULSIS studies enrolled 1,061 IPF patients, while the combined ASCEND and CAPACITY studies enrolled 1,247 patients. The difference in size isn't all that large.
Moving to safety and tolerability:
Ten IPF patients treated with nintedanib suffered heart attacks in the two INPULSIS studies (five in each study) compared to two heart attacks reported in placebo-treated patients (one in each study.) Two of the nintedanib heart attacks were fatal; one of the placebo patients also died.
The rate of serious adverse events listed as "cardiac disorder" was 5% in the nintedanib arms (pooled) versus 5.4% in the placebo arms (also pooled.)
The rate of "serious ischemic disease" reported in the INPULSIS studies was 2.4% in both the nintedanib and placebo arms.
There's some new and interesting liver safety data being reported today for the first time from Boehringer's nintedanib studies. Six patients (0.9%) discontinued nintedanib treatment because of elevations in AST, ALT or bilirubin levels -- all markers for liver toxicity. There were no cases of Hy's Law reported in the studies.
Eight percent of nintedanib patients experienced elevation of ALT or AST three times the upper limit of normal or greater.
The comparable rate of ALT/AST elevations above three times the upper limit of normal for InterMune's pirfenidone was 3%. One case of Hy's Law in a pirfenidone-treated patient was reported.
Investors have previously raised some concerns about the liver safety of pirfenidone, but these new nintedanib data suggest Boehringer's drug is no better, perhaps worse.
As previously reported, the rate of diarrhea in the nintedanib patients was 61.5% and 63.2% in the two INPULSIS studies. The placebo-adjusted rate of diarrhea was 43% and 45%. However, only 5% of patients discontinued from the two studies due to the diarrhea.
Other gastrointestinal-related adverse events of note were 17% and 19% placebo-adjusted rates of nausea. Vomiting was reported in 11% and 7% of patients, adjusted for placebo.
Moving to InterMune's study, rash was reported by 28% of pirfenidone-treated patients compared to 8.7% in the placebo arm -- a 19% difference. The placebo-adjusted rate of nausea attributed to pirfenidone was 23%, vomiting 4%.
There's a lot to digest here already so I won't go into detail on the key secondary efficacy endpoints of the respective IPF studies except to recount that InterMune's pirfenidone demonstrated a progression-free survival benefit while Boehringer showed a reduction in the time to first acute exacerbation in INPULSIS-2 but not INPULSIS-1.
But let's end with some more comparative efficacy data and slides.