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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 details three specific statistical and methodological reasons for the FDA's rejection of the HARMONY 1 study.",
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      "text": "FDA rejected HARMONY 1 for cataplexy indication for 3 reasons:",
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      "text": "The statistically significant finding for cataplexy in HARMONY 1 was dependent on how missing values were handled (i.e., missing or zero values were assigned a value of 0.5; if they were excluded from the analysis, the treatment effect was no longer statistically significant).",
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      "text": "1. Cataplexy was a secondary endpoint in HARMONY 1. There was no prospective plan to control the Type-I error rate for secondary endpoints in this study. 2. The subgroup of interest was defined post hoc based on event(s) that occurred post-randomization, which violates the randomization principle and could lead to invalid conclusions. 3. The statistically significant finding for cataplexy in HARMONY 1 was dependent on how missing values were handled (i.e., missing or zero values were assigned a value of 0.5; if they were excluded from the analysis, the treatment effect was no longer statistically significant).",
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      "text": "The first two studies were to support an indication for excessive daytime sleepiness in adults with narcolepsy, and CTP was the principal study for an indication of cataplexy in adults with narcolepsy. CTP was an attempt at damage control, as the FDA advised that a claim for anticataplectic activity needs to be substantiated with two adequate and well-controlled studies. Some background helps explains why CTP was critical - Bioprojet submitted HARMONY 1 and CTP in support of cataplexy, but received a Complete Response Letter (CRL) where the agency stated HARMONY 1 was not adequate for the cataplexy endpoint for three reasons as elaborated in the summary below from the FDA biometrics review:",
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      "text": "The Agency determined that HARMONY 1 could not be considered as adequate and well-controlled trial for the cataplexy endpoint for the following reasons: 1. Cataplexy was a secondary endpoint in HARMONY 1. There was no prospective plan to control the Type-I error rate for secondary endpoints in this study.",
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      "text": "Source: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/211150Orig2s000StatR.pdf",
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