The InterMune Shocker: What The Wags Are Saying
24 CommentsBy Ed Silverman // May 5th, 2010 // 9:45 am
Last night, a high-flying biotech, InterMune, was brought back down to earth when the FDA issued a surprise rejection of its drug to treat idiopathic pulmonary fibrosis, which Wall Street was betting would generate $1 billion a year or more in annual sales. In anticipation of approval, the stock had increased roughly five times, reaching almost $50 a share - until now. The stock is around $10.
About 100,000 folks in the US suffer from this fatal lung ailment, but InterMune is unlikely to win approval any time soon, because the FDA saked for a new clinical trial of the medicine, called Esbriet or pirfenidone, to prove it delays progression. As TheStreet points out, InterMune should have raised more money after an FDA panel voted 9 to 3 to recommend approval last March. Now it has just about $178 million, not enough to ride out an expensive, lengthy trial (listen to the replay of their conference call here).
So what’s next?
“Introduces New uncertainties: First and foremost these include whether a Japanese trial run by another company, Shionogi, could possibly be re-packaged to satisfy FDA’s request. This seems a longshot, given it is unknown whether FDA would even consider that (differences include geography, dose, design, etc.), and exercising the right to translate patient data could be challenging, time-consuming, and have economic consequences for InterMune…Major model changes included pushing out US launch by three years, lowering probability of success to 50 percent from 95 percent in the US.” - Tom Russo at RW Baird
“We continue to believe that Esbriet is an active agent and see another shot on goal with the
European application with potentially a greater role of the Shionogi data. Although the European decision now becomes much more binary than before, we believe the large potential upside in
the commercial opportunity in IPF is worth the risks…We continue to be convinced of Esbriet’s activity and see a big commercial opportunity. In four randomized Phase II and III trials, Esbriet has shown a positive trend in FVC (forced vital capacity) or VC in all six comparisons with a statistically significant benefit seen in three of the four trials. The consistent benefit, although small, is viewed to clinically meaningful by all MEDACorp pulmonology physicians we spoke to and this view was confirmed by FDA’s advisory panel. Based on physician feedback, we believe the market for IPF is likely much larger than that of pulmonary arterial hypertension.” - Howard Liang of Leerink Swann
“We do not expect Shionogi Pirfenidone Phase III trial will be enough to support FDA approval…However, Pirfenidone approval in Europe remains on the table and we expect a decision from EMA in 1H11. While the likelihood of approval is significantly diminished given yesterday’s decision, we believe there is still a possibility that EMA reaches a different conclusion than FDA. Maintain BUY rating and decreasing PT to $14 from $55.” - Terence Flynn at Lazard Capital Markets
patrons99
I’m a little suprised that the market for IPF is that large. Nearly all patients that I see with pulmonary fibrosis on chest radiographs are long-term cigarette smokers. Hence, they have smoking-related lung disease, not idiopathic.
JaT
Before I saw your comment, 99, I was already thinking your thought. Idiopathic being- we don’t know what caused it. Why isn’t it just being presented for pulmonary fibrosis? Is it because it doesn’t treat all forms of the disease? And if not, then yeah, I can see where FDA might hesitate. Otherwise doctors might be providing a pointless treatment.
Suzanne
This blog mentions it as a scleroderma treatment:
http://rheumination.typepad.com/rheumination/2010/03/more-stuff-that-doesnt-work-for-scleroderma.html
patrons99
Hi JaT -
I’d be curious to know the precise indication they sought from FDA and the study design, inclusion/exclusion criteria, and efficacy endpoints used in the pivotal studies.
IPF is to me a bit of a hodge-podge (poorly defined) condition. It’s a diagnosis of exclusion, after you’ve eliminated the much more common causes of pulmonary fibrosis, e.g. rheumatoid lung disease, scleroderma lung disease, end-stage COPD, pneumoconiosis/occupational lung disease, radiation-induced lung disease, and the like.
JaT
I don’t know how you can have a “precise indication” where idopathic conditions are concerned, but then there is plenty that I do not understand.
They do it with AEDs. The drug indications being for the type of symptoms- rather than the cause of the condition. Science appears to have a long way to go toward curing disease.
Thanks for your take on it.
patrons99
@ Suzanne - I could easily be wrong here…I’m not a pulmonologist. But if their sought-after indication from FDA is IPF, then using it to treat scleroderma lung disease is an off-label use, and probably cannot be marketed as such.
Here’s a couple of links to IPF and scleroderma lung disease that may be helpful.
http://www.pcca.net/IPF.htm
http://www.pcca.net/PulmonaryFibrosis.htm
http://www.pcca.net/SclerodermaLungDisease.htm
Dr Jeffrey Shea, is a practicing pulmonologist in Longview, TX. I’ve referred patients to him. Of course, I think highly of his expertise.
Jackson Roe
Intermune has already received a cia from the OIG for off-label promotion of this drug; therefore the onus may be stronger. They’ve already benefitted from pre-approval sales even though at the time, there were no other treatments on the market.
patrons99
Jackson - could it be that because “at the time, there were no other treatments on the market”, they [Intermune] is effectively getting a compassionate use exemption and expedited review by FDA. In certain respects, having IFP can be likened to having “cancer”.
I could also see where enrollment into such studies might be very slow because IPF is not that common. Again, it would be interesting to compare the language of the indication they sought, to the inclusion/exclusion criteria of the pivotal studies.
Does this drug work for all forms of pulmonary fibrosis? If so, why not just seek a broad indication for ALL pulmonary fibrosis? THAT market would be large. If it doesn’t work for ALL forms of PF, then wouldn’t it just offer “false hope” for some types of PF, e.g. scleroderma lung?
Suzanne
Patrons99 - I don’t have any personal experience with scleroderma, but it is my impression that there are no approved therapies specifically for it - they just treat the symptoms as they occur.
patrons99
Suzanne - yes, it’s very difficult to seek treatment of conditions for which the cause is poorly understood. At least, looking at it superficially, it appears [to me] to involve a fundamental, immune derangement, which is systemic. A clinical database tracking incidence and prevalence would be interesting. More generally, why are there so many diseases which appear to be in significant part, autoimmune in nature? And if they are becoming more frequent, hadn’t we better try to find out why?
Suzanne
Patrons99 wrote, “More generally, why are there so many diseases which appear to be in significant part, autoimmune in nature? And if they are becoming more frequent, hadn’t we better try to find out why?”
You are preaching to the choir.
I have heard that they are getting better at diagnosing AI diseases, so that is why they are becoming more frequent.
JaT
I had this whole thing written on the subject of drug induced lupus- until I bumped my mouse pad.
:/
Now that it’s locked:
“More generally, why are there so many diseases which appear to be in significant part, autoimmune in nature? And if they are becoming more frequent, hadn’t we better try to find out why?”
Look into DILE. My research finds some of the culprits to be
antiepileptics
antihypertensives
antiarrhythmics
antibiotics (odd because you probably wouldn’t be on one for very long)
statins (they should be called anticholestorics- just to fit in)…
Nothing quite like your body attacking itself. The joint issues are well known, but this causes swelling around the heart and lungs- among other things.
It would be a good place to start, in pondering 99s question. Who isn’t on an antisomethingorother?
The good news- DILE is usually reversed on discontinuing the drug. Usually, if you discontinue them soon enough. The bad news for me is- to succumb to seizures is equally dangerous and terrifying. I don’t believe we know everything there is to know on the topic.
Suzanne
JaT wrote, “The good news- DILE is usually reversed on discontinuing the drug.”
That is why, to my way of thinking, it is an adverse event and not truly autoimmune.
JaT
Just saying that- in line with wondering why people are presenting with more instances of autoimmune diseases it is something to consider. More maintenance drugs are being taken. I don’t know if it is an AE- kind of- but it generally takes years to develope. It isn’t really an effect that can be pin pointed in a few years of developement trials. So how can DILE make the list of warnings?
JaT
The good news- DILE is usually reversed on discontinuing the drug. Usually, if you discontinue them soon enough.
And if you don’t?
patrons99
JaT - I think that at the very least we ought to start meticulously tracking the incidence and prevalence of autoimmune diseases. While it feels intuitively like they are becoming more common, we need proof.
With the rapid ascendancy of biologics and ever more “innoculations” being added to the pediatric and adult vaccinations schedules, I have a concern that AI diseases will become even more common over time. Why? Because they are administered parenterally, not orally. Hence, they go directly into the bloodstream, bypassing many of the immune defenses we have in the GI tract.
Suzanne
Patrons99 wrote, “I think that at the very least we ought to start meticulously tracking the incidence and prevalence of autoimmune diseases. While it feels intuitively like they are becoming more common, we need proof.”
Would Humira be on top in 2016 if this wasn’t happening?
http://www.pharmalot.com/2010/05/the-worlds-biggest-selling-drug-in-2016-will-be/
Suzanne
JaT wrote, “The good news- DILE is usually reversed on discontinuing the drug. Usually, if you discontinue them soon enough.
And if you don’t?”
I have trouble understanding why someone would stay on a med that is causing a reaction.
I have read patient stories where they accept the additional diagnosis of lupus, though. It doesn’t seem that they question that it could be DIL; they just post, ‘great, now I have lupus on top of RA (and/or fibro)’. I’m seeing the same thing happening with psoriasis.
patrons99
Suzanne - re: the 2016 best seller list. For many of those drugs, without mentioning any names specifically, I am VERY concerned that the “treatment” may be much worse than the “cure”. Where’s the long-term outcome data (all cause morbidity, mortality, and survival benefit) for any of the best sellers?
Suzanne
I agree. Words not cannot describe how difficult it is to have make these decisions for a young child.
I do find some humor in this journey though. I’ll share something that was posted on a support forum:
“I had a first meeting with a rheumatologist who was trying to get me onto immuno-suppressants. When I refused, he asked why?
I told him that I had not seen many people get to remission or cured on immuno-suppressants.
He said in his best Irish accent, ” That’s not so, there’s a waiting room full of them out there.
JaT
Hi Suzanne,
You wrote “I have trouble understanding why someone would stay on a med that is causing a reaction.”
Maybe I have the common affliction of a person unable to see their own right path. I’m sure open to suggestions that won’t have me going into status epilepticus. It comes down to what could kill me faster I suppose. Or if I’d like to continue to be able to think. Or which is more miserable, seizures or pain.
I’ve looked a lot at how to safely quit phenytoin. One event had me trying alternatives. I couldn’t take them- and/or- they didn’t work. Moreover, trying them found me in danger. To safely quit this damned drug would probably require a rehab facility of sorts. And for what? The luxury of seizing?
The saddest thing is the number of people being put on this and similar things for other reasons. You want to yell Don’t Do It at everyone. It’s a complete trap. Would I have taken it- knowing what I know now? I was in bad shape having partial seizures almost daily. Maybe it would be easier now, simply by knowing what is going on and what to expect.
More to the point though- I think the practice of treating symptoms is a sad statement in this day and age. No one seems to be looking for cures for the things that don’t kill rapidly. VNS and surgery rarely eliminate the need for drugs. Blood pressure meds don’t cure hypertension. Statins, if they did cure high cholesterol, wouldn’t start being approved for use in people without the condition. Insulin doesn’t cure diabetes. Etc..
patrons99, I agree that delivery into the blood stream, IM, through injections, could hasten a reaction. Oral drugs get there too though. Maybe that explains the delay in DILE symptoms with their long term use. Especially in children without fully developed brains and bodies, it is worrisome.
Suzanne
JaT, I sincerely apologize as I meant no offense to you. I’m sorry you are in a position to have to choose the lesser of the evils. My understanding would be that just because one antiepileptic, antihypertensive, antiarrhythmic, or antibiotic induced symptoms of lupus, another one might not. On that basis, my thinking would be to continue the ’same’ therapy on a different med.
JaT
Things don’t always translate well in print. I sure was not offended and didn’t mean to sound as if I was. Just saying.
JaT
Also, it isn’t as if I don’t appreciate that drugs are available to treat symptoms. Just that it would be nice to see the kind of work being done to end that dependency in the meantime. Not sure drug makers have the motivation when they refer to their products as block busters.
Anywho… sorry to go so far off topic once again.