BioMed News: Antigenics, Shire, King Pharma, Delcath Systems

On 6/1/09, Antigenics (AGEN) announced results of an interim analysis from the Company’s ongoing global patient survival registry, which showed that patients with kidney cancer at intermediate risk of disease recurrence demonstrated an approximately 46% lower risk of death when treated with Oncophage (vitespen) cancer vaccine compared with observation (n = 362; P = 0.036; hazard ratio [HR] = 0.54). The interim analysis from the patient registry, INSPIRE, reflects a median follow-up of 4.5 years from the largest, randomized Phase 3 kidney cancer trial ever completed to date in the adjuvant setting. The patient registry was launched in order to confirm encouraging overall survival trends observed from the Phase 3 non-metastatic kidney cancer study. Final results from INSPIRE are expected mid-2010.

In October 2008, AGEN submitted a marketing authorization application to the European Medicines Agency (EMEA) requesting conditional approval for Oncophage in earlier-stage, localized renal cell carcinoma (kidney cancer). AGEN expects a decision on its European marketing application by late 2009 and the Company has not filed for U.S. marketing approval of the drug as of yet. On 10/21/09, AGEN announced that the Committee for Medicinal Products for Human Use (CHMP) of the EMEA has verbally informed the Company at an oral meeting to anticipate a negative opinion on the marketing authorization application (MAA) for Oncophage in early-stage, localized renal cell carcinoma.

On 10/21/09, Shire (SHPGY) announced that it plans to file a BLA with the FDA for REPLAGAL (agalsidase alfa), its enzyme replacement therapy for Fabry disease, by the end of 2009. The Company also announces that a treatment protocol for REPLAGAL, filed at the request of FDA, has been approved, and that it will support emergency IND requests as part of the early access program in place due to the supply restriction of the only currently marketed treatment for Fabry disease in the US. REPLAGAL is a human form of enzyme alpha-galactosidase A (a-Gal A) manufactured in a human cell line by gene activation.

REPLAGAL is approved in 45 countries worldwide. REPLAGAL is not currently approved for commercial sale in the U.S. REPLAGAL is the only human-cell-line-derived form of enzyme replacement therapy (ERT) that is indicated for the long-term treatment of patients with a confirmed diagnosis of Fabry disease (alfa-galactosidase A deficiency).

On 10/21/09, King Pharma (KG) announced that it received a complete response letter (CRL) for its NDA seeking approval of CorVue (binodenoson) for injection as a cardiac pharmacologic stress agent for use as an adjunct in SPECT (single-photon-emission computed tomographic) cardiac imaging intended for use in patients with or at risk for coronary artery disease (CAD) who are unable to perform a cardiac exercise stress test. King is currently evaluating the Agency’s CRL complete response letter and expects to respond to the questions as quickly as possible.

On 7/28/09, an FDA Advisory Panel voted that King’s experimental heart imaging agent, CorVue, failed to demonstrate equivalent imaging results as an older, approved agent (adenosine). In an 11-5 vote, the FDA Advisory Panel stated that the Company’s study results failed to establish a high degree of similarity between images generated by CorVue and adenosine.

On 8/31/09, Delcath Systems (DCTH) announced the FDA granted orphan drug status to doxorubicin, an approved chemotherapy agent, for the treatment of primary liver cancer. The Company said it tested doxorubicin with its unique drug delivery technology, Percutaneous Hepatic Perfusion (PHP), which results in significantly higher doses (e.g. 10X the FDA approved standard dosing with 100X exposure of drug to the tumor site) of anti-cancer drugs such as doxorubicin to the liver without exposing the patient's entire body. Delcath plans to carry out the necessary clinical work for a regulatory submission of PHP with doxorubicin.

On 8/25/09, DCTH reported that it has exceeded 90% enrollment for its pivotal Phase 3 Metastatic Melanoma Trial which will enroll a total of 92 patients. This study is testing the PHP System for the regional delivery of melphalan to the liver to treat patients with metastatic melanoma (a deadly type of skin cancer) who have tumors in the liver, which cannot be removed by surgery (unresectable). On 10/21/09, DCTH announced that its pivotal Phase 3 Metastatic Melanoma Trial has met its goal of 92 patients and is fully enrolled. With the achievement of complete enrollment, the company remains on-track for a FDA submission of its Delcath PHP System with melphalan by mid-2010 based on previous guidance.

Disclosure: No positions

See my full disclaimer at MikeHavRx.com (bottom of any page).

Comments

[dreamdivers:]

Um Mike, rather than just regurgitating AGEN's press releases, perhaps you might try explaining why the EMEA gave Oncophage such a quick thumbs down. I know actual analysis is not something Biomedreports is very familiar with, but you might try it sometime.

Oct 21 02:53 PM

[User 503141:]

Excellent point dreamdivers. It would be more helpful in evaluating AGEN's announcement to have a better understanding of why EMEA is going to reject Oncophage. That would give us a heads up on further work that AGEN needs to do or that Oncophage really does not work.

Oct 21 03:03 PM

[Mike Havrilla:]

dreamdivers, there is a market for an informational database service of pending clinical trials and FDA decisions that compiles and updates this type of data for investors and traders in one location. Analyzing and writing opinions for the over 400 entries on a daily basis would be an entirely different level of service and require a full-time staff of analysts.


On Oct 21 02:53 PM dreamdivers wrote:

> Um Mike, rather than just regurgitating AGEN's press releases, perhaps
> you might try explaining why the EMEA gave Oncophage such a quick
> thumbs down. I know actual analysis is not something Biomedreports
> is very familiar with, but you might try it sometime.

Oct 21 03:28 PM

[User 476730:]

Mike:
Today A. Feuerstein has mentioned in The Street that Phase III trials for kidney cancer and skin cancer failed in the past.

Is that true?

I don't know how to read the info above.

Oct 21 07:18 PM

[Mike Havrilla:]

User 476730, Adam correctly pointed out in his article that the reason for no US approval and the negative opinion for EU approval announced today for Oncophage (aka vitespen) lies in the fact that the clinical trials did not achieve their prospective (i.e. before the trial started) primary outcomes in the pivotal Phase 3 trials that I have referenced below in melanoma and kidney cancer. "Positive data” from the trials was only generated after the fact by analyzing the data (data mining) to identify subsets of the patient population which may have benefitted from treatment in the study.

1.) melanoma trial: J Clin Oncol. 2008 Aug 1;26(22): 3819.
www.ncbi.nlm.nih.gov/p...

Intention-to-treat analysis showed that overall survival in the vitespen arm is statistically indistinguishable from that in the PC arm. Exploratory landmark analyses (data mining) show that patients in the M1a and M1b substages receiving a larger number of vitespen immunizations survived longer than those receiving fewer such treatments. Such difference was not detected for substage M1c patients.

2.) kidney cancer trial: Lancet. 2008 Jul 12;372(9633):145-54. Epub 2008 Jul 3.
www.ncbi.nlm.nih.gov/p...

No difference in recurrence-free survival was seen between patients given vitespen and those who received no treatment after nephrectomy for renal cell carcinoma. A possible improvement in recurrence-free survival in patients with early stage disease who received vitespen will require further validation.

From AGEN website / PRs: The end-of-study results showed that in a substantial subset of patients (n = 362) at intermediate risk for disease recurrence (this is data mining since the substantial subset was not identified prior to the study), Oncophage demonstrated an improvement in recurrence-free survival of approximately 45 percent. For intermediate-risk patients, there was also a trend towards improved overall survival, the study’s secondary endpoint. The interim analysis from the patient registry, INSPIRE, reflects a median follow-up of 4.5 years from the largest, randomized Phase 3 kidney cancer trial ever completed to date in the adjuvant setting. The patient registry was launched in order to confirm encouraging overall survival trends observed from the Phase 3 non-metastatic kidney cancer study with final results from INSPIRE expected mid-2010.

Mike


On Oct 21 07:18 PM User 476730 wrote:

> Mike:
> Today A. Feuerstein has mentioned in The Street that Phase III trials
> for kidney cancer and skin cancer failed in the past.
>
> Is that true?
>
> I don't know how to read the info above.

Oct 21 08:03 PM

[dreamdivers:]

So in your article today you devote an entire first paragraph to summarizing the "positive" data, which you later admit comes only from the company data mining retrospectively? Meanwhile, you reluctantly admit only when directly questioned that pivotal trials in both RCC and melanoma failed? You guys really should be ashamed, why not just put on cheerleader skirts and make it official.

Oct 21 09:17 PM

[Mike Havrilla:]

dreamdivers, you can review my article archives and easily distinguish between information provided on upcoming data points, regulatory decisions, and clinical catalysts as compared to stocks that I own or write commentaries on.

AGEN is tracked in the FDA Calendar database because it will release an update next year from the patient registry which will impact the stock price. I have never written an opinion piece on AGEN or recommended that anyone buy the stock and have only pointed it out for the pending catalysts in the form of the EMEA decision and clinical data update.

On Oct 21 09:17 PM dreamdivers wrote:

> So in your article today you devote an entire first paragraph to
> summarizing the "positive" data, which you later admit comes only
> from the company data mining retrospectively? Meanwhile, you reluctantly
> admit only when directly questioned that pivotal trials in both RCC
> and melanoma failed? You guys really should be ashamed, why not just
> put on cheerleader skirts and make it official.

Oct 21 09:37 PM

[dreamdivers:]

"it will release an update next year from the patient registry which will impact the stock price."??? You must be joking? Maybe you missed it earlier today, but they issued a small press release which also managed to impact the stock price, unfortunately in a slightly negative way. As I said, you guys really are shameless, it is almost laughable the way in which you almost pretend the EMEA rejection never happened, and look forward to updating the patient registry next year. I'm sure you will hype that one to the rafters. What a joke!

Oct 21 10:04 PM

[Roy Manning:]

I did own some AGEN a month ago but decided to sell it off until the company got European approval (CE Mark). Today AGEN got pummeled down 42% and I am happy I decided to wait for European approval before investing any money. If you are careful you can buy biotech or medical stocks that already have approval of their drugs but have not started to get significant sales yet - ACCP with MuGard's global approval comes to mind as a cheap stock (under 100m capitalization) with great potential that already has won approval for its drug. There are many other cheap already approved biotechs and medical stocks out there - look for these sure thing stocks over the usual -40% failed approval stocks.

Best of luck to all,
Roy Manning

Oct 21 10:04 PM

[NYPharmer1:]

Dreamdiver - i'm amazed at how you trashtalk BMR as well as Mike yet follow diligently :) keep it up; the pendulum swings both ways.

NYPharmer1

Oct 21 11:05 PM

[Robert0713:]

As he said, he maintains a calendar, and rather extensive at that. Here at SA, some of that is provided gratis. If you would care to analyze the prospects of a binary event for some company, AGEN for example, you can refer to the calendar, then do the background research from public information to decide whether some company, AGEN for example, is likely to succeed. AGEN didn't. Some folks who *do* write analysis opinions concluded that AGEN wouldn't. AGEN has stated that they intend to continue with Oncophage. Take the information for what you believe it is worth.


On Oct 21 10:04 PM dreamdivers wrote:

> "it will release an update next year from the patient registry which
> will impact the stock price."??? You must be joking? Maybe you missed
> it earlier today, but they issued a small press release which also
> managed to impact the stock price, unfortunately in a slightly negative
> way. As I said, you guys really are shameless, it is almost laughable
> the way in which you almost pretend the EMEA rejection never happened,
> and look forward to updating the patient registry next year. I'm
> sure you will hype that one to the rafters. What a joke!

Oct 21 11:30 PM

[TX Gal 4Evr:]

KUDOS to Robert0713 and NYPharmer1 for setting the record straight on nitpicking complainers. I'm constantly appalled at those who want 'free info' and 'please serve it on a silver platter' (dreamdivers)!!
Take A.F. out to lunch and leave the SA staff alone to take care of 'real business' that all of us totally appreciate!

Oct 22 12:48 PM

[dreamdivers:]

I think it's almost laughable that Havrilla is now leaving comments on Feuerstein's TSCM article trying to "explain" how the EMEA managed to reject Oncophage, despite the wonderful data mining results.

Oct 22 01:34 PM

[Mike Havrilla:]

dreamdivers, your comments are laughable and misdirected, have you reviewed the article history for AGEN?

seekingalpha.com/symbo...

You don't seem to understand the difference between recommending a stock and providing info about biomed stocks with pending catalysts in a calendar database for subscribers to research further and make their own decisions.

Not to mention the fact that I recommend a strategy (outlined in the extreme trade articles) of investing in a basket of small / micro-cap biomed stocks with pending catalysts well ahead of their binary events and selling before the event occurs.


On Oct 22 01:34 PM dreamdivers wrote:

> I think it's almost laughable that Havrilla is now leaving comments
> on Feuerstein's TSCM article trying to "explain" how the EMEA managed
> to reject Oncophage, despite the wonderful data mining results.

Oct 22 02:24 PM

[User 476730:]

Mike,
I'd like to insist if you could clarify in words that only a shmuck could understand. I'm confused in regards to the kidney cancer study.

So far I believe there are some contradictions:

Study ongoing:
1. From AGEN website / PRs it seems that the Phase 3 non-metastatic kidney cancer study is still ongoing with final results from INSPIRE expected mid-2010.
Was INSPIRE the Phase III study?

Study failed:
1. "... the reason for no US approval and the negative opinion for EU approval announced today for Oncophage (aka vitespen) lies in the fact that the clinical trials did not achieve their prospective (i.e. before the trial started) primary outcomes in the pivotal Phase 3 trials that I have referenced below in melanoma and kidney cancer."
2. kidney cancer trial: Lancet. 2008 Jul 12;372(9633):145-54. Epub 2008 Jul 3.
No difference in recurrence-free survival was seen between patients given vitespen and those who received no treatment after nephrectomy for renal cell carcinoma.


Does the following mean the study was not tested in patients with early stage disease?:
"A possible improvement in recurrence-free survival in patients with early stage disease who received vitespen will require further validation."


What exactly does this mean?:
"Positive data” from the trials was only generated after the fact by analyzing the data (data mining) to identify subsets of the patient population which may have benefitted from treatment in the study.


Bottom line, is phase III for kidney cancer failed and buried or still ongoing with final results (from INSPIRE?) expected mid-2010?

Thanks again.
Fer

Oct 22 02:26 PM

[Mike Havrilla:]

Fer,

INSPIRE reflects the name of the patient registry that was launched in 2007 to confirm the survival trends and to continue collecting overall survival data observed from the Phase 3 kidney cancer study, providing an additional 3 years of data since the trial was closed. The Phase 3 trial is over, and the update next year is for the patient registry.

Recurrence events in patients with stage I or II disease were reported in 19 (15.2%) patients in the Oncophage group and 31 (27.0%) in the observation group, which represents a patient subset with early stage disease.

On Oct 22 02:26 PM User 476730 wrote:

> Mike,
> I'd like to insist if you could clarify in words that only a shmuck
> could understand. I'm confused in regards to the kidney cancer study.
>
>
> So far I believe there are some contradictions:
>
> Study ongoing:
> 1. From AGEN website / PRs it seems that the Phase 3 non-metastatic
> kidney cancer study is still ongoing with final results from INSPIRE
> expected mid-2010.
> Was INSPIRE the Phase III study?
>
> Study failed:
> 1. "... the reason for no US approval and the negative opinion for
> EU approval announced today for Oncophage (aka vitespen) lies in
> the fact that the clinical trials did not achieve their prospective
> (i.e. before the trial started) primary outcomes in the pivotal Phase
> 3 trials that I have referenced below in melanoma and kidney cancer."
>
> 2. kidney cancer trial: Lancet. 2008 Jul 12;372(9633):145-54. Epub
> 2008 Jul 3.
> No difference in recurrence-free survival was seen between patients
> given vitespen and those who received no treatment after nephrectomy
> for renal cell carcinoma.
>
>
> Does the following mean the study was not tested in patients with
> early stage disease?:
> "A possible improvement in recurrence-free survival in patients with
> early stage disease who received vitespen will require further validation."
>
>
>
> What exactly does this mean?:
> "Positive data” from the trials was only generated after the fact
> by analyzing the data (data mining) to identify subsets of the patient
> population which may have benefitted from treatment in the study.
>
>
>
> Bottom line, is phase III for kidney cancer failed and buried or
> still ongoing with final results (from INSPIRE?) expected mid-2010?
>
>
> Thanks again.
> Fer

Oct 22 02:44 PM

[dreamdivers:]

Fer,

I was waiting to see if Havrilla would give you a straightforward, honest answer to a simple honest question, and obviously he is unwilling to do so. So to answer your questions:

1. Both of the Phase 3 trials in melanoma and kidney cancer (RCC) are completed and both failed.

2. AGEN used "data mining" after the RCC trials were completed to identify a subset of patients it believes showed a survival benefit from Oncophage, despite the fact that the trial failed. This patient follow up and its data are called INSPIRE, but it is not a clinical trial.

3. Almost all companies data mine their trials after completion to try to learn something about how well the drug worked in certain subgroups, and perhaps to understand why a trial failed if it did so. It is a useful, legitimate technique, but with important limitations. For example, if you take a large trial with hundreds of patients and break them down into all kinds of small groups, invariably you can find some groups or clusters who do better than others. This finding MAY help you in the future better target your drug and/or redesign your trials again, but it may also be due to random chance alone. And that is why the FDA will almost never put much weight on such retrospective analysis, or approve any drug based on data mining.

The bottom line is that the chances of approval for Oncophage in the US or EU for melanoma or RCC without conducting another pivotal trial are almost zero. The INSPIRE data and updates will no doubt be used to hype the stock once again in the future, which is no doubt why BMR keeps referring to it and ignoring the failed trials so much. It looks like Oncophage is still in Phase 2 trials for glioma, so you still have a chance there.

Oct 22 03:13 PM

[TX Gal 4Evr:]

FYI:

Mike/BMR has only 3 articles published regarding AGEN. Your comments are NOT about the subject at hand, but are directly targeting a researcher! GROW UP and MOVE ON!!!!


On Oct 22 03:13 PM dreamdivers wrote:

> Fer,
>
> I was waiting to see if Havrilla would give you a straightforward,
> honest answer to a simple honest question, and obviously he is unwilling
> to do so. So to answer your questions:
>
> 1. Both of the Phase 3 trials in melanoma and kidney cancer (seekingalpha.com/symbo...)
> are completed and both failed.
>
> 2. AGEN used "data mining" after the RCC trials were completed to
> identify a subset of patients it believes showed a survival benefit
> from Oncophage, despite the fact that the trial failed. This patient
> follow up and its data are called INSPIRE, but it is not a clinical
> trial.
>
> 3. Almost all companies data mine their trials after completion to
> try to learn something about how well the drug worked in certain
> subgroups, and perhaps to understand why a trial failed if it did
> so. It is a useful, legitimate technique, but with important limitations.
> For example, if you take a large trial with hundreds of patients
> and break them down into all kinds of small groups, invariably you
> can find some groups or clusters who do better than others. This
> finding MAY help you in the future better target your drug and/or
> redesign your trials again, but it may also be due to random chance
> alone. And that is why the FDA will almost never put much weight
> on such retrospective analysis, or approve any drug based on data
> mining.
>
> The bottom line is that the chances of approval for Oncophage in
> the US or EU for melanoma or RCC without conducting another pivotal
> trial are almost zero. The INSPIRE data and updates will no doubt
> be used to hype the stock once again in the future, which is no doubt
> why BMR keeps referring to it and ignoring the failed trials so much.
> It looks like Oncophage is still in Phase 2 trials for glioma, so
> you still have a chance there.

Oct 22 04:01 PM

[dreamdivers:]

TX Gal, I will stay here and converse with Fer as long as I care to. If you don't like it, move on yourself. No one was talking to you. No one asked for your opinion. You are obviously a shill.

Oct 22 04:10 PM

[User 476730:]

Thanks guys for the input.

I finally understand how screwed I am with AGEN.

In addition, A. Feuerstein gives a value of the stock (which includes QS-21 approved and marketed) that if correct I'm even more screwed.

Will have to move on.
Thanks and GLTA.

Oct 22 05:16 PM

[User 467679:]

Everyone take some valium and chill out. Now there's a drug that works!

Oct 22 06:35 PM

[BambamPoop:]

Mike,

What happened to your site? mikehavrx.com ? discontinued? or just temporarily down?

bambampoop

Oct 22 10:43 PM

[TX Gal 4Evr:]

AND...you are obviously making bad trading decisions and trying (albeit unsuccessfully) to pin the consequences of those decisions on someone who simply writes factual articles. Do your own DD, invest accordingly and take responsibility for screw-ups! There's facts and there's 'opinions'.....if you are a scientist, doctor or whatever....then give all of us something interesting to think about in lieu of 'bashing'! Pretty simple!


On Oct 22 04:10 PM dreamdivers wrote:

> TX Gal, I will stay here and converse with Fer as long as I care
> to. If you don't like it, move on yourself. No one was talking to
> you. No one asked for your opinion. You are obviously a shill.

Oct 23 12:50 AM

[User 476730:]

By the way,

Does anybody follow other people in Seeking A or any other sites, blogs, etc. who you trust in biotech related stocks?

thanks

Oct 23 10:45 AM

[Mike Havrilla:]

Bam, Was having technical / IT issues with Google's blogger service so I have redirected mikehavrx.com to the ProActiveNewsRoom.com site, which already has a blog, my stock indexes, etc.

Mike


On Oct 22 10:43 PM BambamPoop wrote:

> Mike,
>
> What happened to your site? mikehavrx.com ? discontinued? or just
> temporarily down?
>
> bambampoop

Oct 23 02:18 PM

[Mike Havrilla:]

here is the actual strategy. . . provide subscribers with info on pending biomed catalysts in a calendar format, provide some examples / strategies for how to use the info in the calendar (e.g. Extreme Trading articles, including 85 single digit stocks in my most recent update), and price the service economically so retail investors can affort to subscribe.


On Oct 23 10:53 AM [e-mail] wrote:

> here's havrilla's strategy:
> * Buy before the news
> * pump it up with biomedreports and press releases
> * sell before the news.
>
> What a shameless scammer you are!
>
> <<<I recommend a strategy (outlined in the extreme trade articles)
> of investing in a basket of small / micro-cap biomed stocks with
> pending catalysts well ahead of their binary events and selling before
> the event occurs.>>

Oct 23 02:24 PM

[TX Gal 4Evr:]

YES, there are 3 others that I follow, other than Mike H..... M.E. Garza, Justin Hall and VFC's Stock House. These guys 'tell-it-like-it-is'...or at least 'as they see it'......as opposed to all the 'dreamers' who must interject their 2 cents in order to divert the conversations that the sane people TRY to have on here. I'm new at investing and I read/analyze their opinions/analysis....do my own DD and act upon it accordingly. I'm sure there are others who are highly qualified, however, following several could be confusing to someone like myself.
(I'm thinking that 'dreamdivers'....is just that....the person 'dives in' without looking and dreams they'll be OK...then there's 'hoopdreamerz'...who must jump thru hoops in order to save the dream diver!)<<Have no clue who these fools are, but they are truly disgusting and pathetic.


On Oct 23 10:45 AM User 476730 wrote:

> By the way,
>
> Does anybody follow other people in Seeking A or any other sites,
> blogs, etc. who you trust in biotech related stocks?
>
> thanks

Oct 23 04:25 PM

[User 476730:]

Thanks TX for your input. I also follow all of them. I like to check other views as well (A. Feuerstein) so I can have opposite views to analize.

I also appreciate Dreamdivers input. It is the clear and easy language type of answer I was looking for.

Anybody else who can add some names to follow?
Thanks

Oct 24 10:37 AM

[TX Gal 4Evr:]

You might be interested in stockshaven.com..he's a straight-shooter.
Dreamdivers...gets his kicks by interjecting 'emotion' into his posts and believe me....EMOTION has no place in investing!
After AGEN reports on the 29th, see what Dreamdivers has to say!
Good Luck!


On Oct 24 10:37 AM User 476730 wrote:

> Thanks TX for your input. I also follow all of them. I like to check
> other views as well (A. Feuerstein) so I can have opposite views
> to analize.
>
> I also appreciate Dreamdivers input. It is the clear and easy language
> type of answer I was looking for.
>
> Anybody else who can add some names to follow?
> Thanks

Oct 26 11:33 AM