Lets see how the 2 drugs performed in the FVC<10%, which was primary point for ITMN (met) and secondary for BI (failed)
If you compare the data side-by-side the dominance of pirfenidone is more than clear.
I. From BI release http://us.boehringer-ingelheim.com/news_events/press_releases/press_release_archive/2014/05-18-14-phase-3-inpulsis-trials-new-england-journal-of-medicine-nintedanib-lung-function-idiopathic-pulmonary-fibrosis.html
■More nintedanib versus placebo patients had an absolute decline in FVC of less than 10% in the INPULSIS™-1 trial (70.6% vs. 56.9%, respectively; OR 1.91 [95% CI: 1.32, 2.79])
■This difference did not reach statistical significance in the INPULSIS™-2 trial (69.6% vs. 63.9%, respectively; OR 1.29 [95% CI: 0.89, 1.86])
From ITMN ASCEND data
A 10% decline in FVC in an individual IPF patient is considered clinically meaningful and strongly predictive of a higher risk of mortality. Â At Week 52, 16.5% of patients in the pirfenidone group experienced an FVC decline of 10% or more or death, compared with 31.8% in the placebo group, representing a 47.9% reduction in the proportion of patients who experienced this meaningful decline in FVC or death.
Or to be comparable with BI, 83,5% vs. 68.2%, so 22.43% more patience than placebo group while the BI reported did not reach statistical significance!!!
II. The INPULSIS trials did not exclude patients with normal values for FVC, which is reflected in the fact that the mean baseline FVC was higher in the INPULSIS trials (approximately 80% of the predicted value) than in the ASCEND trial (approximately 68% of the predicted value). More simply, the average patient with idiopathic pulmonary fibrosis in the INPULSIS trials had less severe disease than the average patient in the ASCEND trial.
III. Although the two INPULSIS trials and the ASCEND trial showed that treatment resulted in relative reductions in the rate of decline in FVC, the pirfenidone group in the ASCEND study had a greater annual decline in the mean FVC (−235 ml) than did the placebo groups of both of the INPULSIS studies (−205 ml).
IV. Regarding mortality, 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 compared to only a 30% in nintedanib. Also and most inmportant factor focused mainly from the FDA is that InterMune pooled survival data from ASCEND with the previous phase III CAPACITY studies shows that 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.
V. 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.
- 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%.
So in core side-to-side comparison there is higher efficacy of Pirfenidone.