The Motley FoolBetting on Approval for This Orphan DrugBy Brian Lawler | April 22, 2008
There's nothing more exciting in pharma investing than the release of new clinical trial data. Let's take a look at InterMune's (Nasdaq: ITMN) newest data for its lead drug, pirfenidone, and see if it's up to muster.
Pirfenidone is being tested in two phase 3 studies as a potential treatment for idiopathic pulmonary fibrosis (IPF).
IPF is a chronic, incurable condition of scarring of the lungs that makes breathing very difficult and has no known cause. Many patients die from the disease several years after being diagnosed.
I've previously covered InterMune's overview of pirfenidone and its market opportunity. Results of InterMune's phase 3 pirfenidone studies are due out early next year, but we recently got a glimpse of what sort of data they could produce. Yesterday, InterMune pointed investors to the abstract of a phase 3 study run by the holder of the marketing rights to pirfenidone in Japan, Shionogi; for those following along at home, here's the abstract.
The exciting news for InterMune investors is that there appear to be many similarities between the Shionogi phase 3 study (and the phase 2 study, as well) and InterMune's phase 3 pirfenidone studies. But there are also some key differences between the InterMune and Shionogi studies, and it is the differences that often trip up a drug in clinical trials.
Differences can spell defeat or victory
As any good pharma investor will tell you, it becomes harder to replicate study results as the number of differences between the clinical trials increases. In the case of InterMune's phase 3 studies and the Shionogi studies, any differences between the trials are bad news, because both Shionogi studies appear to have been successful.
The Shionogi phase 2 pirfenidone study, for example, was stopped early by a data-monitoring committee because of the preponderance of positive data (pirfenidone patients' reduced number of acute IPF exacerbations) favoring the drug versus placebo. In the Shionogi phase 3 study, pirfenidone met its primary and most important secondary study endpoints. The drug increased patients' progression-free survival and also showed benefits in lung functioning in what is called a "vital capacity" breath test.
Here are the main areas in which InterMune's phase 3 pirfenidone studies differ from Shionogi's, based on Shionogi's phase 2 study and the abstract details of Shionogi's phase 3 study:
1. InterMune's phase 3 pirfenidone studies are of a different patient population.
Shionogi's studies tested the drug in Japanese patients, whereas InterMune's trial sites are in North America and throughout Europe. Undoubtedly, patient composition will be very different, and it's anyone's guess whether these demographics will mean better or worse odds for success with InterMune's studies. Japanese IPF sufferers could have an easier (or tougher) version of the disease, for instance, or they could be otherwise healthier than North American and European sufferers of IPF, causing them to respond better to pirfenidone (or, for that matter, worse).2. InterMune's phase 3 studies use a different maximum dosage than Shionogi's.
InterMune chose to test pirfenidone at a 33% higher dose in most patient groups than Shionogi used for its studies (2,400 mg daily for InterMune phase 3 studies, versus 1,800 mg daily for Shionogi studies). This decision was likely made because North American and European IPF sufferers weigh more than Japanese IPF sufferers. Nonetheless, this higher dosage strength in a different patient group does open the door for more unexpected, serious adverse events to occur in some patients -- although pirfenidone was previously tested at even higher doses in an open-label phase 2 study, so this may be a minor issue.3. InterMune's phase 3 studies are for a different length of time.
Shionogi's phase 2 study was cut short by its data-monitoring board after most patients had only received nine months of pirfenidone, and in its phase 3 study, Shionogi tested the drug over 52 weeks of dosing. InterMune's phase 3 studies will give patients pirfenidone for 72 weeks. If pirfenidone truly is superior to placebo, then these longer studies will highlight its efficacy even more. But this also means the possibility for new, more serious adverse events that only occur over longer-term dosing.4. InterMune's phase 3 studies are much larger than Shionogi's.
InterMune's two phase 3 studies will are composed of 400 and 320 patients, and Shionogi's phase 2 and 3 studies recruited 109 and 275 patients, respectively. For one thing, a larger study increases the probability that a drug that truly works will be successful in clinical testing (a phenomenon that's referred to as "the power of a study"). Also, regulatory agencies and doctors always appreciate the extra clarity on adverse events and efficacy in subgroups of patients (women vs. men, for example) that a larger study provides.5. InterMune's phase 3 studies use a slightly different primary endpoint than Shionogi's phase 3 study did.
Some may consider it a negative that InterMune is using "forced vital capacity" (essentially a measure of how powerfully a patient can breathe) as its pulmonary-functioning primary endpoint in its phase 3 studies, compared to the "vital capacity" pulmonary-functioning primary endpoint Shionogi used in its phase 3 study.