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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 critiques the authors' interpretation of ECG/QTc data in the HAROSA 2 trial, pointing out potential bias or omission.",
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      "text": "The paper falsely claims no significant difference in QTC between pitolisant and placebo",
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      "text": "Paper states no significant QT increase – but only for previous narcolepsy trials",
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      "text": "Fatality in HAROSA 2 due to heart attack",
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      "text": "The authors state that the death (heart attack) and QTc changes were not likely related to study drug but no explanation is provided for this assessment – and we emphasize that patients with significant cardiovascular disease were excluded from the study.",
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      "text": "Furthermore, the authors summarize the cardiovascular results in Harosa 2 by saying that “No key changes were found in...ECG test results...the changes reported in QTc (QTcF >450 ms and elongation >60 msec) did not differ significantly between pitolisant and placebo.” However, there were 7 patients total with QTcF prolonged greater than 60 msec (combining >60 with >450) vs. only one in placebo. The authors state that the death (heart attack) and QTc changes were not likely related to study drug but no explanation is provided for this assessment – and we emphasize that patients with significant cardiovascular disease were excluded from the study. In addition, the discussion states that in previous narcolepsy trials, patients “did not show any significant increase QTc” – but do not make a similar statement for this trial, because they once again fail to compare baseline to treatment. There is no reason narcolepsy vs. sleep apnea patients in HAROSA 1 and 2 would metabolize pitolisant differently.",
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      "text": "TEAEs leading to study drug withdrawal were reported for three patients (1.5%) in the pitolisant group and two patients (3.0%) in the placebo group. Serious TEAEs were reported for two patients (1.0%; one prolonged QT interval on the ECG and one cardiopulmonary failure leading to death) during pitolisant treatment and considered unlikely to be treatment related and in none of the patients receiving placebo.",
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      "text": "period. Accordingly, results reported with pitolisant in the previous randomized controlled trials in patients with narcolepsy (14, 15) did not show any significant increase in QTc. A recent 1-year open-label",
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      "text": "Our results confirm the favorable safety profile of pitolisant already reported in patients with narcolepsy (14, 15). No key changes were found in physical examination parameters or vital signs, depressive symptoms, and ECG or laboratory test results during the study. The changes reported in QTc (QTcF, >450 ms and elongation >60 ms) did not differ significantly between pitolisant and placebo. The pitolisant to placebo subject",
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      "text": "“No key changes were found in…ECG test results…the changes reported in QTc (QTcF >450 ms and elongation >60 msec) did not differ significantly between pitolisant and placebo.” — Authors of Harosa 2 study",
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      "text": "Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193861/",
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