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Joseph Krueger

 
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  • Somaxon, soon a buy-out target? [View instapost]
    We seemed to have reached some middle point here. Your veiwpoint is obviously well supported by your knowledge. Admittedly, after our discussions I am much more optomistic about Silenor's chances for approval. So thanks for your insight.
    But again, trying to get in the FDA's head, which as of late is downright schitzophrenic (are they getting pressure from the BO adminstration in preparation for health care reform?), my feeling is that they will reject it or delay it. Why? In simple terms,the FDA review panel asks 3 simple questions and votes on each one:
    1) Is the drug safe?
    2) Does the drug provide a meaningful benefit?
    3) Should it be approved for marketing (Do the benefits outweigh any potential risks)?

    Take the recent example of pirfenidone from ITMN: The votes were
    1)9 to 3
    2)7 to 5
    3)9 to 3
    All of these are inter-connected, of course, and the summary question 3 is the key one. But as you can see, there are differing opinions for each part. And the summary vote does not gaurantee approval....there are examples like Savient's Krystexxa for gout had winning 9 to 3 panel vote for question 3 and got rejected in the end anyway.

    In the case of Silenor, alot of issues were brought up during this 3-part approval process, and namely 1 and 2, which lead to a no vote on 3 twice now. Are 1 and 2 really resolved in the panel's mind? Then there is the third question....I think Silenor is more like Kryestexxa. The problem with Kryestexxa was a infrequent allergic reaction. The FDA decided that since gout is a non-life theatening disease, the risk does exceeds the benefit.
    Think about it- and be fair and unbiased:
    Is Silenor effective- rejection two.
    Is Silenor safe- rejection one.
    Are sleeping problems life threatening- no.
    Like Kryestexxa- why takes the risk with a questionably effective and even if ever so slightly questionably safe drug for a non-life threatening disease?
    It is not my opinion so much as what I think the FDA's opinion will be- and that is what matters. And Silenor is make-it-or-break-it for SOMX....how confident do you need to be? Pretty damn sure in this case, you stand to lose 75% of your investment just like the last two times.
    Mar 10 09:35 PM | Likes Like |Link to Comment
  • Somaxon, soon a buy-out target? [View instapost]
    Very nice response. I cant really argue against your points, since I am just speculating and trying to read between the lines of public information and get inside the FDA panel's heads. You or I dont have any information to substantiate our arguments.
    The FDA does not reject, it only does not approve. In other words they dont prevent reapplications, they only reject the ones submitted to them. It also provides guidance before trials and after CRLs to help but in the end they decide what they decide in a sometimes baffling manner. So dont interpret their suggestion for a class 1 as anything but providing guidance as how to move through the regulatory process.
    But I agree SOMX is much closer to getting approval than ever before; I still dont think it will be enough. Most likely it will be delayed asking for a post-marketing approval plan to evaluate QT interval. In simple terms drug exposure is the dose multiplied by time; a low dose for a long time has the same (theoretical) pharmacological effect as a high dose for a long time. So if you are taking chronic low dose doxepin every night to sleep two years later the cardiac tox may show up even though it didnt show up acutely. The FDA does not assume anything- most likely the FDA will want to see some evidence of this in the indicated population and better REMS
    Also, Exalgo by CRXX got held up on multiple REMS revisions. Admittedly it is a different class of drugs but there is your counterpoint.
    Mar 8 10:14 PM | Likes Like |Link to Comment
  • Somaxon, soon a buy-out target? [View instapost]
    As a follow up to my comment, let me explain what I meant better.
    Is Silenor closer to approval this time? Yes. But it will still be rejected.
    The first FDA letter in Feb 2009 was concerned about QT interval; the second in December 2009 was concerned about efficacy. The fact that the QT interval was not mentioned the second time doesnt mean it is resolved; they can bring it up again if they want. But the efficacy issue is not resolved, so SOMX is repackaging the whole thing in a class 1 resubmission to gain an indication for a sub-population of adults and the elderly where it showed efficacy. The FDA asked them to submit a REMS (risk mitigation strategy).
    Now ask yourself this: Why a REMS? If doxepin is so safe, cannot be abused, etc; why a REMS?
    Anyone who understands FDA regulation knows the answer. But for those who don't, here it is:
    (We dont have access to all the data, so these are assumptions, but it seems pretty clear from what is going on)
    THE POPULATION THAT THEY SHOWED CARDIAC SAFTEY IN IS NOT THE SAME POPULATION THAT THEY ARE SEEKING THE INDICATION FOR!
    You cant make assumptions that the specific population your indication (label) serves is the same as the general population (as far as the FDA is concerned) So the FDA still likely has concerns about QT intervals in this population. Rather than go back and gather this data, they will want a REMS strategy that makes sure that only this specific population which saw benefit will recieve the drug, with an evaluation of cardiac health before prescribing. Then they will have to have a protocol which monitors cardiac safety in patients taking the drug. REMS usually takes a couple tries with the FDA- go back and look at the history of REMS revision for many drugs.
    Or they will want post-approval studies in this population to prove their is no risk (it could get pulled from the market if this doesnt go well). What doctor/patient will go to all this trouble when they can just take a generic without all this hassle? What health insurance company will allow these tests? So even if it gains approval, not market share.

    However this time the FDA will likely say: The modest efficacy in the sub-population not worth the unproven safety. Your REMS strategy is not sufficient. Go back and prove saftey for your indication or supply us with a REMS stategy that addresses these issues. REJECTED.
    Mar 7 10:17 AM | 1 Like Like |Link to Comment
  • Somaxon, soon a buy-out target? [View instapost]
    I do agree with you:
    "Let the FDA do its job".
    The issue is what the FDA thinks, not what you or anyone else thinks. The regulatory issues the FDA is concerned about have very little to do with any of your points-
    Beyond this, the FDA has seemingly been especially agressive in rejecting drugs with any even potential saftey issues for a non-life thereatening disease (see XNPT).
    The FDA has made their stance on Silenor pretty clear multiple times.....considering that the only thing that is changing in the class 1 resubmission is the REMS strategy, none of the other issues that the FDA brough up in the past 2 rejections have been remedied.
    I stand by all my other points about its market share and M/A speculation.
    Mar 5 09:04 AM | Likes Like |Link to Comment
  • Somaxon, soon a buy-out target? [View instapost]
    That is actually a supported opinion but simply wrong.

    Your main point is that safety and efficacy data are not being
    considered further, only the indication or "label"; who can take the
    drug might be the change made in the class 1 resubmission. You are suggesting that because Silenor was only "effective" in one group studied, they will simply ammend the indication to exclude other groups and it will get approved.
    You are also saying that every other class 1 resubmission will has been approved. I doubt it, but even if true, so what- none of those drugs are in the sticky situation Silenor is in. It doesnt matter whether or not it is class one or class two, that really has no bearing on the outcome, it is only a class one because it is not including any additional safety or efficacy data. What Somaxin is going to include in the class one resubmission is a Risk Evaluation and Mitigation Strategy; nothing else new.

    Even with this, Silenor will still not get approved this time: The cardiac toxicity is a looming issue; the effect of long term use was not evalutated. Given that it was marginally effective for sleep, the FDA will not take a chance on a drug that doesnt even seem to work, for a non-threatening issue like insomnia. This is the same reason it was rejected the last two times- nothing has changed there.

    A questionably effective drug with potential cardiac toxicity for a non life threatening medical problem for which there are safe generic drugs out there already?
    Say that out loud and listen to how stupid it sounds.

    The last round of rejection the FDA stated that the NDA "did not meet the approval standard for efficacy due to a lack of robustness of sustained subjective sleep maintenance efficacy in adults with primary insomnia." Although the FDA did not raise any new clinical safety issues, the QT interval problem still did not go away.
    The FDA requested the company to submit an amended new REMS, earning the class 1 resubmission; there is no significance to it other than that.

    As far as the whole M&A nonsense, no one is going to buy SOMX for Silenor even if it was approved. Silenor is not a blockbuster drug, it is a lower dosage of a generic drug which will have a very small label use on the outside chance it gets approval. Ambien is already generic, and it doesnt have these problems; Silenor will not capture any market share in the remote chance it is approved. Even worse than this, if approved, the FDA will likely ask SOMX to run long term safety studies looking at the QT interval post marketing approval- what company would take on that risk?
    Mar 4 11:00 PM | 2 Likes Like |Link to Comment
  • Poniard Pharmaceuticals: Oversold, Undervalued, Poised for Short Squeeze [View article]
    We did see that short squeeze rally from under $2 when I wrote this article up to $2.50 based on the conference CRC trial results. The trial did meet its primary endpoint, but did not offer a clear picture of equal or better efficacy for picoplatin. Unfortunately, a Wall Street Journal article was released the morning after the weekend conference stating that the trial was a failure and the stock would drop to $1. This was not a completely unfair assessment, but was indeed negatively biased by a trusted opinion and the sellers took control. Being experienced in the market, I ran with the herd and sold my PARD position to avoid losses and thus not longer have a position in PARD.
    These trial results were not powered for efficacy, and although the data was not overly promising it certainly does not ensure that picoplatin cannot meet its primary endpoint of less neurotoxicity with lack of inferiority to oxaliplatin in a trial powered to show such. I am looking for a bargain price ("dont try to catch a falling knife") to re-enter PARD and hold for the phase II PCa results update in March.
    Jan 30 08:10 PM | Likes Like |Link to Comment
  • Poniard Pharmaceuticals: Oversold, Undervalued, Poised for Short Squeeze [View article]
    I forgot Medarex is now part of BMS
    Jan 27 06:09 PM | Likes Like |Link to Comment
  • Poniard Pharmaceuticals: Oversold, Undervalued, Poised for Short Squeeze [View article]
    I am thinking that antibodies against IL-6 (Centocor; now J&J) or B7-H1/PD-1 interaction (Medarex) would be the way to approach this.
    Jan 27 06:07 PM | Likes Like |Link to Comment
  • Poniard Pharmaceuticals: Oversold, Undervalued, Poised for Short Squeeze [View article]
    I assume you are talking about Bavituximab, in trials for treating cancer and hepatitus C. Bavituximab recognizes a complex of PS and the PS-binding protein, ß2 glycoprotein. Although it is probably does not target tumor-specific vasculature apecifically, as PPHM touts it, the science has strong rationale. If it shows efficacy against tumors, then it can potentially treat tumors that have failed Avastin, as they are different mechanisms. If it targets viral infected cells, then it may be a better way to treat HCV than interferons. One advantage to the antibody format is that it can be coupled to radioisotopes and chemotherapuetics for better efficacy. Will it work? Who knows. I wish I could offer more insight. PPHM is betting on it, and I dont think it is a bad bet. Given that PPHM stock is close to its long term support range in the $2-3 range, it is probably a good value right now and a good one to put in the piggy bank....but it will be a while before we hear about any significant developments.
    Jan 26 10:09 PM | Likes Like |Link to Comment
  • Poniard Pharmaceuticals: Oversold, Undervalued, Poised for Short Squeeze [View article]
    jay, thanks for all the comments- you have given me alot of homework. I will have to look into the others, but I can comment off the top of my head about NOV-002.
    I do not like NOV-002,. If you read carefully here
    novelos.com/html/our_p...
    you can see they have been running these trials in Russia since 1998! Why hasnt it made any further progress in the EU or US that where it is now?
    Also, the NSCLC trial is poorly designed. The Primary Outcome Measures is "Overall survival during the length of the trial, length of the trial is approximately two years after last patient in [ Time Frame: 16 months". This is the worst possible outcome one can choose for a trial as there is so much variablility that far out that the statistical power is compromised. There are almost 900 patients, so that will help, but looks at the types of trials the giants Roche, Genentech, etc who have blockbuster drugs approved in second line NSCLC use- progression free survial at 3 months, not overall survival at 16
    Note that they recently finished enrolling, but the trial wont be done for another 16 months. Also NSCLC is a very crowded field. However adding NOV-002 to the current chemotherapy SOC is better than trying to replace it all together.
    The phase II trials still have to go through phasee III, which makes the phase III NSCLC trial quite pivotal- are you willing to take this gamble?
    The company already has a market cap of over $150MM, which is the most you can expect for a company with a product in the NOV-002 stage. I dont see much upside in the near term, with alot of potential downside.
    Jan 26 09:22 AM | Likes Like |Link to Comment
  • Poniard Pharmaceuticals: Oversold, Undervalued, Poised for Short Squeeze [View article]
    PARD news:
    Phase II trial for picoplating in CRC et primary endpoint.
    www.prnewswire.com/new...
    Jan 24 11:31 AM | Likes Like |Link to Comment
  • Poniard Pharmaceuticals: A Rebound Is Overdue [View article]
    this article seems oddly familiar
    Jan 23 06:48 PM | Likes Like |Link to Comment
  • Poniard Pharmaceuticals: Oversold, Undervalued, Poised for Short Squeeze [View article]
    And here is the short squeeze today, driven by the conference presentation....
    Jan 22 12:00 PM | Likes Like |Link to Comment
  • The Future of Biotech: Party Like It's 1999 [View article]
    I have not found a site which summarizes phase II trials. For phase III trials and upcoming FDA decisions, Biomedreports.com (Mike Havrilla) offers a wealth of free information about these and the sector in general. They offer a subscription service for $20 per month which gives you access to more detailed information and gives you trading alerts based on up to the minute news. You can perform alot of DD even if you are not a paid subscriber by following their press releases and public view articles. The subscription service is not overly priced and does provide a valuable service over what you can pick apart from the free content.
    Jan 18 02:58 PM | 2 Likes Like |Link to Comment
  • The Future of Biotech: Party Like It's 1999 [View article]
    Wall Street Teacher wrote:
    "Best stategy is to buy a basket of Ph IIs and wait for the fun to begin"

    Indeed....building that portfolio now! Thanks for any suggestions.
    Jan 18 12:15 PM | 1 Like Like |Link to Comment
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