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  "documentTitle": "Harmony Biosciences (HRMY)",
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  "notes": "The slide uses a table from a Lancet paper to argue that pitolisant's performance was inferior to modafinil, contradicting the company's narrative.",
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      "text": "Harmony 1 trial paper, published 2013 in The Lancet – pitolisant was inferior to modafinil on the primary endpoint of excessive daytime sleepiness as measured by Epworth Sleepiness Scale; final ESS score in pitolisant arm still indicates excessive sleepiness; also inferior on cataplexy reduction",
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      "text": "The trial showed that pitolisant was inferior to modafinil in reducing excessive daytime sleepiness (EDS), the primary endpoint, and also inferior in cataplexy.",
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      "text": "A remarkable feature of Bioprojet’s clinical trials is an obvious pattern of failure, followed by attempts at damage control. HARMONY 1 compared pitolisant to placebo or modafinil, a $50/month generic wakefulness-promoting drug that’s typically the fist line of treatment. The trial showed that pitolisant was inferior to modafinil in reducing excessive daytime sleepiness (EDS), the primary endpoint, and also inferior in cataplexy. The study claimed pitolisant is slightly superior to placebo, and used that to persuade the FDA that it was still worthy of approval as it’s purportedly safe and not a scheduled substance. The second pivotal trial, HARMONY 1-bis, was an outright debacle and never published. The design was similar to HARMONY 1. Pitolisant failed to show statistically-significant reduction in EDS or cataplexy vs. either placebo or modafinil, and in fact did even worse vs. modafinil than in HARMONY 1.",
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      "text": "In post-hoc analyses, pitolisant was superior to placebo but not non-inferior to modafinil in terms of improvement in cataplexy rate from baseline (table 2, appendix). In other post-hoc analyses, the percentage of responders (with final ESS scores of 10 or lower) also differed between the pitolisant and placebo groups and were similar between pitolisant and modafinil (table 2).",
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      "text": "Harmony 1 trial paper, published 2013 in The Lancet – pitolisant was inferior to modafinil on the primary endpoint of excessive daytime sleepiness as measured by Epworth Sleepiness Scale; final ESS score in pitolisant arm still indicates excessive sleepiness; also inferior on cataplexy reduction — The Lancet",
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      "text": "Source: https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(13)70225-4/fulltext",
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      "text": "Placebo, Pitolisant, Modafinil columns with Baseline, Final, Change over trial metrics for ESS.",
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