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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 highlights a discrepancy between the reported trial results and the underlying patient-level data regarding dosage and efficacy.",
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      "text": "In other words, patients on the higher dose did far worse, and it appears that statistical significance vs. placebo was driven by the tiny 20mg subgroup.",
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      "text": "ESS score improvement: 70%",
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      "text": "A second table shows that the 8 patients who remained on 20mg had ESS score improvements 70% greater than those on 40mg (-9.1 vs. -5.1). In other words, patients on the higher dose did far worse, and it appears that statistical significance vs. placebo was driven by the tiny 20mg subgroup.",
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      "text": "Patients in the treatment arm could receive 10, 20, or 40 mg of pitolisant. Critically, the paper fails to disclose the number of 31 pitolisant patients by dose, and nor does it show efficacy results on EDS or secondary measures for dosage subgroups.",
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      "text": "Two tables buried in the EMA review explain why the paper was less than forthcoming. One reveals that 19 patients (61%) had to be titrated to the highest dose (40mg), suggesting lack of efficacy during the first half of the trial.",
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      "text": "The mean final ESS score in the 18-patient 40mg group was 13.4 vs. 15.6 for placebo – that is, the results were not statistically significant for the largest subgroup. Furthermore, this calls into question the chart of ESS scores by week (slide ___), which shows that the largest drop is in weeks 2 and 3 – if true, why were 18 of 31 patients titrated to double the dose after week 3?",
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      "text": "Source: https://www.ema.europa.eu/en/documents/assessment-report/wakix-epar-public-assessment-report_en.pdf",
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      "text": "Table 10. Summary of stable dose stage [% (n)] in Harmony I study.",
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      "text": "Table 11. Summary of ESS by pitolisant stable dose [Mean ± SD] in Harmony I study.",
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      "kind": "title",
      "text": "HARMONY 1 and the other pivotal trials also used a flexible dosing schedule, and failed to show a dose response – another red flag.",
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      "kind": "title",
      "text": "Harmony 1 data by dose per EMA review of pitolisant, 2015 – BF2.649 is pitolisant",
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