A.J.:
Glad you got the red flags you needed, and Miljenko was certainly bold in making the correct investment call.
But.... I have been an observer, afraid to make a call. So, you got your flags elsewhere.
I read this quite differently than most who are commenting. I don't believe that it's open and shut. I wasn't a shareholder..... don't remember ever owning the stock. I probably have, but certainly not recently. But I took a small "just fun to participate" position today, near the close. This is high drama, and I couldn't resist.
I surmise.... guess, speculate, whatever..... that the animosity inherent in this review is proud scientist (Koerner) versus proud scientist (Lange), with the element that Lange et al. could use PRs to advance their side of the story while FDA scientists have no vehicle for making their observations public. That ticks off those who work at FDA, no end..... they sit and watch as a company builds market cap, using PRs and investor presentations (webcast!!) to politicize the road. It would tick me off.
OTOH, Koerner is, IMO, vindictive. His review drips vindictive. He focuses on the "what if", and engages in commentary about risk from QTcies in the context of efficacy that did not impress him. He goes out of his way to comment about QTc in the context of his view of efficacy. It's an attack. The question? Is he justified? It does sound a bit disconcerting that CVTX has not done an exhaustive screen of agents known to prolong QTc. I certainly would have.
But many of those on that panel tomorrow will be clinicians who deal with patients in pain. Those patients KNOW what causes the pain. Chronic angina is an indication BEGGING for something new. Dr. Koerner is a lab scientist, not a physician. He can flippantly refer to P = 0.03 as marginal. I'm not impressed by the data either, but patients generally elected to continue on open label after trials had ended. Maybe things are different, if you've got chronic, severe angina.
So.... I guess that I'd lean toward a "no" vote tomorrow....... I'd guess that the "hypokalemia, etc." angle will throw enough light on the unknown, and FDA is clearly signaling that they need the routine six thousand patient exposure for a chronic-use drug. But, if Lange et al. walk in with data to address the concerns of FDA scientists, apart from the part about being shy about three thousand patients? It will then be great drama. Otherwise, I'm afraid that we're talking outrageous comedy.
:-)
Here's the best place to navigate from.........
fda.gov
And, for those who, like me, didn't understand what the heck Koerner's stopper was......
emedicine.com
Trends Pharmacol Sci. 2003 Dec;24(12):619-25.
Assessing predictors of drug-induced torsade de pointes.
Belardinelli L, Antzelevitch C, Vos MA.
CV Therapeutics, 3172 Porter Drive, 94304, Palo Alto, CA, USA
Torsades de pointes (TdP) is a malignant polymorphic ventricular tachyarrhythmia that can be caused by drugs that induce electrophysiological changes. Although the number of drugs known to cause TdP has increased in recent years, there is no cell-based assay, in vitro heart preparation or animal model that predicts the potential of a drug to induce TdP in humans. Nevertheless, certain electrophysiological events are known to be associated with the development of TdP. For example, a drug that prolongs action potential duration, induces early afterdepolarizations and ectopic beats, and increases dispersion of ventricular repolarization is likely to cause TdP. By contrast, a drug that does not induce these changes is unlikely to cause TdP. The exact relationship between these electrophysiological events and the development of TdP has not been defined, but the potential of a drug to elicit these events might predict its pro-arrhythmic risk.
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Cheers, and good luck all!
Rick, clueless and just rambling |
