InterMune Inc. (ITMN)

[ghmm]

> What are the salient differences in trial design? T.i.a.
Genisi had asked that a while back (mabe it was on SI?) I'll try to list them but I may miss something.
Of note while entry criteria differed. Intermune asserts the enrolled patients were incredible similar in terms of baseline characteristics of lung function (vital capacity in Japan and FVC for the CAPACITY). I believe they talk about this is on their call following the ATS presentation if you have access to it or a transcript for more precise details.
1. Japanese patients vs non Japanese. The company has stressed no known difference in metabolism of Pirfenidone in different populations.
2. Weight difference Japanese patients notably lighter.
3. The high dose in the Shionogi study was 1800mg vs. 2400 in CAPACITY (company claims on mg/kg basis equates to the same). Noteable though is the low dose (which should statistical significance in the primary end point of the Shionogi study is the same in both namely 1200mg a day).
4. Primary End point is change in VC in Shionogi vs. Change in FVC in CAPACITY. Company states that pulmonolgists they consult with say as long as obstruction is eliminated (and is part of entry criteria) should be comparable.
5. Treatment duration 52 weeks in Shionogi, 72 in Capacity.
6. Number of patients 250 in Shionogi (randomized 2:2:1 H:P:L) vs. 320 and 400 in the two CAPACITY studies (actually 779 enrolled but don’t know the exact numbers in each trial). Randomization in Capacity 1 is 1:1 H:P and in Capacity 2 is 2:2:1 H:P:L

How can an investor handicap the upcoming Pirfenidone results based on Japanese data?
This is a difficult question to answer and based on the Shionogi data even more so. I think part of the long delay in Japaneese approval was the Shionogi data was not clean. Namely 30% drop outs and O2 saturation (the original end point) did not show significance. To me the main risk is:
1) IPF is a very heterogeneous not well (compared to other diseases) understood disease.
2) Less advanced patients are enrolled may lead to the good old placebo doing better than expected. Where Dan Welch gained some additional respect (in my book) was increasing the study duration to 72 weeks (from 60). The other thing the company has stressed is the identification of patients with confirmation of their IPF through a centralized reading of HRCT before enrolling them.
3) Longer duration could lead to the possibility a treatment benefit is temporary and is lost. I think the companies’ prior failure in 2 Phase 3 Actimmune studies leads this as low probability [i.e. I think Dan is pretty smart and would have reduced the length by 8 weeks to match Shionogi rather than increase it].

Those are the negatives. In my posts various places I have stated reasons for optimism. To me some of the biggest are:
1-Prior success in IPF studies though they are a bit messy (Phase 2 stopped early, Phase 3 noted above). Additional there is an open label phase 2 in advanced patients with very encouraging results when compared to expected outcome and they were in decline.
2-In numerous (granted small) studies of fibrotic disease Pirfenidone has shown efficacy.
3-There is no approved therapy. While steroids, NAC and some other agents are used none is a solution and the ultimate (in the near-mid term) solution is likely some cocktail. So the hurdle should be low.


PS I'll dig up some slides and e-mail them to you