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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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      "text": "We speculate whether Harmony may have misled the FDA, given the rampant statistical tricks across its papers and trials – using a 40mg dose to determine the plasma level in normal metabolizers, but only a 17.8mg dose in the three patients who were poor metabolizers.",
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      "text": "Figure 3: Pitolisant Pharmacokinetics in CYP2D6 Poor Metabolizers",
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      "text": "FDA review docs versus full prescribing information from the label",
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      "text": "And a fourth red flag, one we find potentially nefarious: it’s unclear what dose was used to determine the plasma level in poor vs. normal CYP2D6 metabolizers. We speculate whether Harmony may have misled the FDA, given the rampant statistical tricks across its papers and trials – using a 40mg dose to determine the plasma level in normal metabolizers, but only a 17.8mg dose in the three patients who were poor metabolizers. This would make the plasma level increase in poor metabolizers appears less worse than it is. Note below that the FDA CDER Clinical Pharmacology Review states that it was 40 mg, while the prescribing instruction in the label – which contains the graph – states that it was 17.8 mg. Notably, the ClinicTrials.gov entry doesn’t mention dose at all.",
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      "text": "CYP2D6 Genetic Deficiencies: The PK of pitolisant in PMs of CYP2D6 vs. Normal metabolizers (NMs) of CYP2D6 was assessed in 8 genotyped healthy adult, male subjects in a mass balance clinical study (P15-02). The PK after single dose as well as after steady state (on day 7) at 40 mg dose (in salt form) was used to compare the exposure in PMs (N=3) vs NMs (N=5). CYP2D6 alleles tested and\nCYP2D6 Poor Metabolizers\nThe pharmacokinetics of pitolisant were evaluated in 3 subjects who were CYP2D6 poor metabolizers (PMs) and 5 subjects who were CYP2D6 extensive metabolizers (EMs). All subjects received WAKIX 17.8 mg daily for 7 days. Exposure of pitolisant in CYP2D6 PMs is summarized in Figure 3.",
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      "text": "Source: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000ClinPharmR.pdf; : https://www.wakix.com/assets/pdf/WAKIX_pitolisant_tablets_PI_Dec_2022.pdf",
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