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  "documentTitle": "Harmony Biosciences (HRMY)",
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  "authorName": "Scorpion Capital",
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  "presentationDate": "2023-03-28 00:00:00",
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  "notes": "The slide uses a 'before-after' logic to expose a flaw in regulatory reliance on single-dose data. The red box highlights the critical 'Upper limit TQT' values in the corrected table.",
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      "kind": "callout",
      "text": "Corrected plasma levels show QT prolongation quickly spikes to dangerous levels, with no safety margin, and becomes dangerous even at the upper limit CI at the dose on the label",
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      "text": "Single does plasma levels upon which the FDA relied massively underestimate the risk of QT prolongation",
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      "text": "QT prolongation: 49 msec",
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      "text": "At 120 mg, QT prolongation is estimated at 22 msec with an upper confidence interval of 49 msec – a red alert level. Pitolisant’s PK profile indicates that a subset of patients can easily hit the plasma levels associated with 120 mg, given massive CYP2D6 liability and drug-drug interactions, as well as poor metabolizers with liver or kidney issues. The data also shows that even at the labeled dose of 35.6mg, the upper limit confidence interval is already past the danger threshold at 12 msec.",
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      "text": "Source: Pharmacology analysis commissioned by Scorpion Capital",
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      "text": "Corrected for multiple dose at steady state assuming a 51% SD",
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      "kind": "table",
      "text": "Actual Data from Tables 2 and 3, Sha et al., Eur J Clin Pharmacol, 2016",
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      "text": "The regression analysis clearly shows that when single-dose plasma levels upon which the FDA relied are corrected to reflect steady-state levels, there is no safety margin and QT prolongation quickly spikes to dangerous levels.",
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