RE: Pirfenidone info

[Guest guest]

Thanks, I have been following this also with fingers crossed.

Steve59 from WA IPF 2006

Reply-To: Breathe-Support To: Breathe-Support Subject: Pirfenidone infoDate: Wed, 23 Apr 2008 17:18:16 -0700 (PDT)

Hi everyone. Just wanted to pass along this article that was sent to me by a friend who's worked in the pharmaceutical industry for many many years. It's got some interesting information comparing the ongoing clinical trials for Pirfenidone to the earlier Japanese trials. I've got as many problems as anyone with Intermune but it is an interesting article and has a hopeful tone. (The article was in the 4/22/08 Motley Fool)

Beth

Age 48 Fibrotic NSIP 06/06

Change everything. Love and Forgive

Betting on Approval for This Orphan Drug

By Lawler April 22, 2008

3 Recommendations

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), ion 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.

[Guest guest]

Beth

I share the same hopes. However, the only place I get them is from the

fact the trials do continue and haven't been shut down. I just get more

hopeful the deeper trials go as it indicates that (1) its unlikely any

huge problems have been found and (2) it is unlikely that its been

clearly shown to hurt or even not to help.

Now, as to getting any better sense from the press releases originating

from Intermune as this one did, I don't get any. They are still a

desperate company in desperate need of investors and a proven history as

a company of fraudulent and criminal behavior.

Still if they hit upon something good we'll all take it. If the worst

company in the world wants to come hand me $10 million to give to the

charities of my choosing, I'll take it. If the worst company in the

world finds a treatment that helps with PF, I'll be happy.

>

> Hi everyone. Just wanted to pass along this article that was sent to

me by a friend who's worked in the pharmaceutical industry for many many

years. It's got some interesting information comparing the ongoing

clinical trials for Pirfenidone to the earlier Japanese trials. I've got

as many problems as anyone with Intermune but it is an interesting

article and has a hopeful tone. (The article was in the 4/22/08 Motley

Fool)

>

>

> Beth

> Age 48 Fibrotic NSIP 06/06

>

> Change everything. Love and Forgive

>

>

>

> Betting on Approval for This Orphan Drug

> By Lawler April 22, 2008

> 3 Recommendations

>

> 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), ion 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.

>

[Guest guest]

Bruce,

I realize that the author of this article got most of his info directly from InterMune...not exactly a sterling source to say the least. However I thought the comparison of the Shionogi study to the North American studies was interesting. If nothing else it highlights how differently clinical trials can be set up. It's certainly not cut and dried and as they say in some respects studies can be structured to gain the types of results they want.

It is as you point out though at least hopeful that the studies remain ongoing and it's starting to look as though there may be some type of treatment for some folks sometime in the not too distant future. Let's keep our fingers crossed!

Beth

Age 48 Fibrotic NSIP 06/06

Change everything. Love and Forgive

Re: Pirfenidone info

BethI share the same hopes. However, the only place I get them is from thefact the trials do continue and haven't been shut down. I just get morehopeful the deeper trials go as it indicates that (1) its unlikely anyhuge problems have been found and (2) it is unlikely that its beenclearly shown to hurt or even not to help.Now, as to getting any better sense from the press releases originatingfrom Intermune as this one did, I don't get any. They are still adesperate company in desperate need of investors and a proven history asa company of fraudulent and criminal behavior.Still if they hit upon something good we'll all take it. If the worstcompany in the world wants to come hand me $10 million to give to thecharities of my choosing, I'll take it. If the worst company in theworld finds a treatment that helps with PF, I'll be happy.>> Hi everyone. Just wanted to pass along this article that was sent tome by a friend who's worked in the pharmaceutical industry for many manyyears. It's got some interesting information comparing the ongoingclinical trials for Pirfenidone to the earlier Japanese trials. I've gotas many problems as anyone with Intermune but it is an interestingarticle and has a hopeful tone. (The article was in the 4/22/08 MotleyFool)>>> Beth> Age 48 Fibrotic NSIP 06/06>> Change everything. Love and Forgive>>>> Betting on Approval for This Orphan Drug> By Lawler April 22, 2008> 3 Recommendations>> There's nothing more exciting

in pharma investing than the release ofnew 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 tomuster.> Pirfenidone is being tested in two phase 3 studies as a potentialtreatment for idiopathic pulmonary fibrosis (IPF).> IPF is a chronic, incurable condition of scarring of the lungs thatmakes breathing very difficult and has no known cause. Many patients diefrom the disease several years after being diagnosed.> I've previously covered InterMune's overview of pirfenidone and itsmarket opportunity. Results of InterMune's phase 3 pirfenidone studiesare due out early next year, but we recently got a glimpse of what sortof data they could produce. Yesterday, InterMune pointed investors tothe abstract of a phase 3 study run by the holder of the marketingrights to pirfenidone in Japan, Shionogi; for those following

along athome, here's the abstract.> The exciting news for InterMune investors is that there appear to bemany similarities between the Shionogi phase 3 study (and the phase 2study, as well) and InterMune's phase 3 pirfenidone studies. But thereare also some key differences between the InterMune and Shionogistudies, and it is the differences that often trip up a drug in clinicaltrials.> Differences can spell defeat or victory> As any good pharma investor will tell you, it becomes harder toreplicate study results as the number of differences between theclinical trials increases. In the case of InterMune's phase 3 studiesand the Shionogi studies, any differences between the trials are badnews, because both Shionogi studies appear to have been successful.> The Shionogi phase 2 pirfenidone study, for example, was stopped earlyby a data-monitoring committee because of the preponderance of

positivedata (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 studyendpoints. The drug increased patients' progression- free survival andalso showed benefits in lung functioning in what is called a "vitalcapacity" breath test.> Here are the main areas in which InterMune's phase 3 pirfenidonestudies differ from Shionogi's, based on Shionogi's phase 2 study andthe abstract details of Shionogi's phase 3 study:> 1. InterMune's phase 3 pirfenidone studies are of a different patientpopulation.> Shionogi's studies tested the drug in Japanese patients, whereasInterMune's trial sites are in North America and throughout Europe.Undoubtedly, patient composition will be very different, and it'sanyone's guess whether these demographics will mean better or worse

oddsfor success with InterMune's studies. Japanese IPF sufferers could havean easier (or tougher) version of the disease, for instance, or theycould be otherwise healthier than North American and European sufferersof IPF, causing them to respond better to pirfenidone (or, for thatmatter, worse).> 2. InterMune's phase 3 studies use a different maximum dosage thanShionogi's.> InterMune chose to test pirfenidone at a 33% higher dose in mostpatient groups than Shionogi used for its studies (2,400 mg daily forInterMune phase 3 studies, versus 1,800 mg daily for Shionogi studies).This decision was likely made because North American and European IPFsufferers weigh more than Japanese IPF sufferers. Nonetheless, thishigher dosage strength in a different patient group does open the doorfor more unexpected, serious adverse events to occur in some patients --although pirfenidone was previously tested

at even higher doses in anopen-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 boardafter most patients had only received nine months of pirfenidone, and inits 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 studieswill highlight its efficacy even more. But this also means thepossibility for new, more serious adverse events that only occur overlonger-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 320patients, and Shionogi's phase 2 and 3 studies recruited 109 and 275patients, respectively. For one thing, a larger

study increases theprobability that a drug that truly works will be successful in clinicaltesting (a phenomenon that's referred to as "the power of a study").Also, regulatory agencies and doctors always appreciate the extraclarity on adverse events and efficacy in subgroups of patients (womenvs. men, for example) that a larger study provides.> 5. InterMune's phase 3 studies use a slightly different primaryendpoint than Shionogi's phase 3 study did.> Some may consider it a negative that InterMune is using "forced vitalcapacity" (essentially a measure of how powerfully a patient canbreathe) as its pulmonary-functioni ng primary endpoint in its phase 3studies, compared to the "vital capacity" pulmonary-functioni ng primaryendpoint Shionogi used in its phase 3 study.> When drugmakers switch primary endpoints between trials, bad studyresults are sometimes more likely. This was the case with

AtheroGenics(Nasdaq: AGEN) last year, when it switched endpoints between phase 2 andphase 3 trials. In the case of InterMune's very slightly tweakedpulmonary-functioni ng primary endpoint, I don't have any major concernsabout the minor difference between tests, though.> This list is just a subset of the differences between InterMune'sphase 3 studies and the Shionogi clinical trials. I'm sure we'll learnabout other clinically important differences when Shionogi presents thefull results from its phase 3 pirfenidone study at the American ThoracicSociety conference in late May.> Enterprising investors can further compare InterMune's pirfenidonestudies to the previously linked Shionogi studies by clicking on theInterMune phase 3 pirfenidone study overviews at clinicaltrials. gov(here and here).> Betting on an orphan> Specialty-pharma analysts often set themselves up for embarrassment

bypredicting positive study results for a drug too soon. Since only oneout every five drugs that begins human clinical study testing goes on toreceive FDA marketing approval, drug failures and analyst embarrassmenthappen 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, whatmakes the drug exciting is that Shionogi (and others in previousstudies) have produced consistently positive clinical studies with it.> Admittedly, there is an infinite number of ways for drugmakers to runa clinical study poorly and mess up its results. But I still have to saythat the evidence that pirfenidone works, and that it will work inInterMune's phase 3 studies, is in its favor.> I'll even go out on a limb (something pharma and biotech analysts hateto do) and predict

that InterMune's pirfenidone studies will be asuccess and will go on to get FDA and EMEA regulatory approval. Thatsaid, no clinical trial is ever a lock to produce good data, and even adrug that works can fail in clinical testing because of statisticalchance.> Currently, there are no FDA-approved drugs to treat IPF. Consideringthat other drugmakers like United Therapeutics (Nasdaq: UTHR), BioMarin(Nasdaq: BMRN), ion Pharmaceuticals (Nasdaq: ALXN), and Actelionwill likely see (or have seen) impressive profits after gainingregulatory approval for drugs to treat small orphan indications, I havelittle doubt that Rule Breakers pick InterMune will make boatloads ofcash from pirfenidone if it is successful in phase 3 testing.Thankfully, we have the Shionogi studies to give us a better ideawhether this success will occur next January.>

[Guest guest]

Beth

Yes, when you look at clinical trials you often see the primary measure

to be very limited in scope with more secondary. Intermune also runs

their trials much differently in terms of them managing the trials as

opposed to something like the Revatio trials where the IPF Centers are

managing them.

Another thing generally on trials is the very limited demographic. They

have to do that to avoid variables. For instance, my FVC was already too

low the first time I had PFT's to qualify for the Pirfenidone trials.

Both Pirfenidone and Revatio have DLCO requirements for their trials,

but opposite ones. Pirfenidone requires DLCO to be greater than 35% and

Revatio requires it to be less than 35%. So, in general, the Pirfenidone

studies are keyed to an early stage IPF patient and the Revatio trials

are geared more to someone in a middle stage.

I also find it interesting (and its true with both of those drugs) to

see trials being run on a drug against many different conditions and

diseases some of which don't have apparent similarities but may in some

medical way.

> >

> > Hi everyone. Just wanted to pass along this article that was sent to

> me by a friend who's worked in the pharmaceutical industry for many

many

> years. It's got some interesting information comparing the ongoing

> clinical trials for Pirfenidone to the earlier Japanese trials. I've

got

> as many problems as anyone with Intermune but it is an interesting

> article and has a hopeful tone. (The article was in the 4/22/08 Motley

> Fool)

> >

> >

> > Beth

> > Age 48 Fibrotic NSIP 06/06

> >

> > Change everything. Love and Forgive

> >

> >

> >

> > Betting on Approval for This Orphan Drug

> > By Lawler April 22, 2008

> > 3 Recommendations

> >

> > 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-functioni ng primary endpoint in its phase 3

> studies, compared to the " vital capacity " pulmonary-functioni ng

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-functioni ng 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), ion 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.

> >

>