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Avanir Pharmaceuticals, Inc. Message Board

  • yho356 yho356 Jul 5, 2009 9:00 PM Flag

    FYI Newbies:Why I like AVNR, part2

    With Zenvia, we already know that the 30/30 formulation works, but the FDA was concerned about the 20msec QT delay in the heart with the 60/60 formulation and they were concerned about the nausea, dizziness and somnolence side effects, which will be disastrous to people who have the underlying condition for PBA (eg Multiple Sclerosis; they may fall down stairs). So Avanir is looking into a 30/10 formulation. PK/PD analysis showed that a 30/10 formulation would have 67% reduction of quinidine (one of the ingredients in Zenvia) in the bloodstream versus the 30/30 formulation, but efficacy would be only down by 25%. Further modelling showed that 25% efficacy would bring the disease from 20 episodes a week, down to 1 or 2. And there was no risk of Torsades de Pointes (a heart conditon brought about by QT prolongation for the 30/10 formulation, as tested on surgically excised rabbit heart slices). There was still a 10msec QT delay (same as in the 30/30 formulation) as detcted in humans patients. But we need to put the 10msec into context. Normal QT is 440msec; you need to get up to 470-480msec before you are considered a 'borderline' case of Prolonged QT. You need to be at >500msec QT (a >60msec prolongation greater than normal baseline) before there is concern that you may be considered a Prolonged QT case. So things look pretty positive. We just need to know that the dizziness, somnolence and nausea can be extenuated down to accepatable levels. But even under the 30/30 dosage, this was experienced only by a small minority of the patients, and it was mild to moderate.
    So the question is whether the FDA is scared too sh!tless after the Cox-2 inhibitor scandal to let a drug with a 10msec QT prolongation through. Even though I got the numbers for the QT intervals above from a documents that I found in the FDA site (line 339 & lines 592-599 of http://www.fda.gov/ohrms/dockets/ac/03/briefing/pubs/prelim.pdf , also line 800 quotes "drugs that prolong the mean QT/QTc interval by 5-10 msec under conditions of maximum effect have also not been clearly associated with risk. Drugs causing a mean 10-20 msec increase under conditions of maximum effect are of concern, but have been approved if they appear to have important therapeutic roles", and page 11 of http://www.questpharm.com/PDF/iche14qtc[1].pdf and in Wikipedia: http://en.wikipedia.org/wiki/Long_QT_syndrome). But this is a drug that makes people feel sane and gives them their lives back (almost like an anti-depressant). This drug can get them to participate in society again--with both friends and relatives, which the patient has shunned before due to the uncontrolled crying/laughing episodes. And there is the story of when Jesus met the Prodigal Son who was guilty of avarice, greed and gluttony. But Jesus was much harder on his brother, who shunned himself from friends and family. So you can see what a huge waste of human life it is to shun yourself from family and friends. So I am sure if there is no adverse effects in the on-going the Phase 3 trial, the FDA will let it through. [continued, see: Part3]

    Yuen Ho
    theWorldIsOurs.com

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