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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 Wikipedia table to demonstrate the complexity of CYP2D6 phenotypes to undermine the validity of the FDA's small-sample study.",
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      "text": "Limiting a study to n=3 such participants suggests an attempt to cherry-pick and present misleading data that understates the variability.",
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      "text": "The FDA CDER Clinical Pharmacology Review contains a bit more information about the CYP2D6 PK study, but it appears they were only provided with a summary and not the underlying data. The red flags are obvious. First, it had only 8 patients, and only 3 were poor CYP2D6 metabolizers – in other words, the FDA’s estimate of steady-state plasma levels and dosage adjustment are based on pharmacokinetics in merely *three* poor metabolizers. The metabolic genotype/phenotype of CYP2D6 varies widely from individual to individual, leading to massive variability in plasma levels. Limiting a study to n=3 such participants suggests an attempt to cherry-pick and present misleading data that understates the variability. CYP2D6 has dozens of phenotypes, and depending on the phenotype an individual’s level of CYP2D6 function may be none, little, decreased/intermediate, normal, or rapid. For example, Wikipedia lists a table of dozens of CYP2D6 phenotypes and their level of activity.",
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      "text": "Source: https://en.wikipedia.org/wiki/CYP2D6",
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