Betting on Approval for This Orphan Drug

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.

When drugmakers switch primary endpoints between trials, bad study results are sometimes more likely. This was the case with AtheroGenics (Nasdaq: AGEN  ) last year, when it switched endpoints between phase 2 and phase 3 trials. In the case of InterMune's very slightly tweaked pulmonary-functioning primary endpoint, I don't have any major concerns about the minor difference between tests, though.

This list is just a subset of the differences between InterMune's phase 3 studies and the Shionogi clinical trials. I'm sure we'll learn about other clinically important differences when Shionogi presents the full results from its phase 3 pirfenidone study at the American Thoracic Society conference in late May.

Enterprising investors can further compare InterMune's pirfenidone studies to the previously linked Shionogi studies by clicking on the InterMune phase 3 pirfenidone study overviews at clinicaltrials.gov (here and here).

Betting on an orphan
Specialty-pharma analysts often set themselves up for embarrassment by predicting positive study results for a drug too soon. Since only one out every five drugs that begins human clinical study testing goes on to receive FDA marketing approval, drug failures and analyst embarrassment happen quite often. (Exhibit A: my prediction about GPC Biotech's (Nasdaq: GPCB  ) Satraplatin eventually getting FDA approval last year.)

Even with InterMune's weak patent estate surrounding pirfenidone, what makes the drug exciting is that Shionogi (and others in previous studies) have produced consistently positive clinical studies with it.

Admittedly, there is an infinite number of ways for drugmakers to run a clinical study poorly and mess up its results. But I still have to say that the evidence that pirfenidone works, and that it will work in InterMune's phase 3 studies, is in its favor.

I'll even go out on a limb (something pharma and biotech analysts hate to do) and predict that InterMune's pirfenidone studies will be a success and will go on to get FDA and EMEA regulatory approval. That said, no clinical trial is ever a lock to produce good data, and even a drug that works can fail in clinical testing because of statistical chance.

Currently, there are no FDA-approved drugs to treat IPF. Considering that other drugmakers like United Therapeutics (Nasdaq: UTHR  ) , BioMarin (Nasdaq: BMRN  ) , Alexion Pharmaceuticals (Nasdaq: ALXN  ) , and Actelion will likely see (or have seen) impressive profits after gaining regulatory approval for drugs to treat small orphan indications, I have little doubt that Rule Breakers pick InterMune will make boatloads of cash from pirfenidone if it is successful in phase 3 testing. Thankfully, we have the Shionogi studies to give us a better idea whether this success will occur next January.


Read/Post Comments (0) | Recommend This Article (5)

Comments from our Foolish Readers

Help us keep this a respectfully Foolish area! This is a place for our readers to discuss, debate, and learn more about the Foolish investing topic you read about above. Help us keep it clean and safe. If you believe a comment is abusive or otherwise violates our Fool's Rules, please report it via the Report this Comment Report this Comment icon found on every comment.

Be the first one to comment on this article.

Sponsored Links

Leaked: Apple's Next Smart Device
(Warning, it may shock you)
The secret is out... experts are predicting 458 million of these types of devices will be sold per year. 1 hyper-growth company stands to rake in maximum profit - and it's NOT Apple. Show me Apple's new smart gizmo!

DocumentId: 627019, ~/Articles/ArticleHandler.aspx, 11/27/2014 1:42:23 PM

Report This Comment

Use this area to report a comment that you believe is in violation of the community guidelines. Our team will review the entry and take any appropriate action.

Sending report...


Advertisement