Biotech Values

[ghmm]

Some more thoughts on Pirfenidone

I know everyone is eagerly awaiting news on 191 (me too I wish it was someone other then the French, I haven’t had too good of success with them in past investments but maybe the focus on Pirfenidone should be moving up a bit more in peoples minds. I have been reviewing some of the calls and journal articles and have some thoughts….

On Enrollment
1. I am thinking there is a good chance of beating even my mid year early enrollment estimate. Here is the thinking… The Shionogi Phase 2 http://ajrccm.atsjournals.org/cgi/content/full/171/9/1040 enrolled 105 patients between November 2000 and January 2001 that with only 25 sights. That would be more then 1.4 patients per sight per month (given that the time is < 3 months unless enrollment started 11/1 and ended 1/31) and probably the 25 sights didn’t all start recruiting on day 1.
2. If the Capacity trials sight is up-to-date and accurate http://www.capacitytrials.com/wt/page/index we have 60 NA sights accepting patients and 14 still awaiting and there are 28 sights outside NA accepting and 20 awaiting. Granted Japan has very good healthcare system so just to be conservative making a rough guess at how the sights may have ramped along with using 1 patient/sight/month (much less then Shionogi Phase 2) month by month could be…
Month Est. # Sites Patients Enrolled In Month Total Enrollment
May ‘06 15 15 15
June ‘06 30 30 45
July ‘06 45 45 90
August ‘06 60 60 150
September ‘06 75 75 225
November ‘06 90 90 315
December ‘06 100 100 415
January ‘07 100 100 515
February ‘07 100 100 615
*Trials started enrolling patients April 27 with expected enrollment of 585 (325 in 3-arm with up to 70 centers and 260 in single dose vs. placebo)
3. As early as the June Needham call the company referred to Investigator interest being very high and patient interest being high (at first I took this as normal PR but now I think it could be enrollment). A month later at the Jefferies conference InterMune said (paraphrased) Investigator interest very, very high and wouldn’t be surprised if beat that enrollment. Though already optimistic. Speaking to excitement shooting to enroll sooner. OK, one more reference in the October CE Unterberg call perhaps a Freudian slip but said CAPACITY should finish enrolling by end of next QUARTER (I think he meant to say next year)

I don’t think enrolling at a fast rate is material information to disclose and probably since the Shionogi results are just around the corner its in InterMune’s interest to wait till then just in case they decide to alter the study (e.g. they decide to dramatically increase enrollment for the power but can then claim interest is extremely high having already enrolled over X amount so we can do it in the same time frame).

On The CAPACITY Trials
1. The Shionogi Phase 2 was stopped by the DSMB early (6 months stopped but data collected for 9 months) due to acute exacerbation in one arm which turned out to be the Placebo arm. OK, many were critical of the trial stopping early and also argued that the 6 and 9 month data were not adequate.
2. Less known is the fact that an NIH study of Pirfenidone in patients with Pulmonary Fibrosis resulting from Hermansky-Pudlak Syndrome (a very rare genetic disease one type has a high incidence in Puerto Rico) was also stopped early for (positive) efficacy
3. The CAPACITY trials have an arm with HIGHER dose (2400 mg as 3 800mg doses) then the Shionogi Phase 2 (1800mg max dosage as 3 600mg doses -- I don’t know the Phase 3 dose but would think it is comparable to the Phase 2). The 800mg dose has been tested before in other Pirfenidone trials. While Pirfenidone does have some side effects (most notably a high incidence of photosensitivity) compared to other treatment the number discontinuing treatment was very low. One would speculate that a higher dose should be at least as efficacious as the Shionogi dose.

Am I saying that the capacity trial could be stopped early??? Yes and No, it is a long shot but there is DSMB monitoring and if one arm is having serious adverse events in a meaningful way it seems ethical to do so. The main thing I am concluding is that with much more rapid enrollment the time frame for outcome/potential to market is much closer then announced even without DSMB stopping.

With the Roche cash and funding what I am wondering more about is why partner Pirfenidone? If it fails (Shionogi Phase 3 results poor) then no one will give you anything anyway. If the results are successful I think the uptake of this drug will be extremely rapid judging not only by unmet medical need, but also what appears to be very high patient interest and rapid trial enrollment. So unless the company does not see premium pricing potential (20K+/yr) then it makes a lot of sense (too me) to set up EU commercial operations with a small (50-100) targeted sales force. What will be the cost 10-20 million for the sales force and even if double that for infrastructure and marketing it will be recouped quickly! I think Encysive with Thelin (though we don’t know yet how they are doing) and BioMarin with Naglazyme are very good recent examples