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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 the FDA's 'wait-and-see' posture and specific concerns about seizures as a safety signal for the drug pitolisant.",
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      "text": "FDA review indicates its “special interest” in seizures, which are mentioned several times as an area of potential concern",
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      "text": "A reported ICSR of epilepsy is notable given the nonclinical findings and prior reports of epilepsy in the postmarketing period. The serious ICSR of epilepsy concerned a 36-year-old female patient with a prior medical history of epilepsy who experienced increased frequency of seizures after exposure to pitolisant. Pitolisant was discontinued after 2 months of treatment. The outcome of the case is unknown.",
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      "text": "Seizures and convulsions are also adverse events of special interest for this application; however, none of these events were reported as serious adverse events in narcolepsy clinical trials. Because seizures and cardiovascular events are of special interest in this development program, the SAE of transient ischemic attack (reported by one patient in the HARMONY III trial) is also notable. A summary of the case narrative is below.",
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      "text": "The FDA conveys its keen interest in “seizures and convulsions” several times – which we think is problematic for Harmony for two reasons. First, the FDA’s database now contains a number of serious adverse event reports related to seizures, indicating a safety signal; and two, seizures are often one of the first symptoms of QT prolongation. We note a paper on the subject: “long QT syndrome accompanied by a seizure episode is often misdiagnosed as primary epilepsy.”",
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      "text": "The FDA also noted a seizure in a European post-marketing Serious Individual Case Safety Report, stating that while none were observed in clinical trials, that the case report “is notable” and that “seizures and cardiovascular events are of special interest.”",
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      "text": "QT prolongation and cardiac events are not the only ones where the FDA’s reviews indicate the agency’s skittishness and a wait-and-see posture pending safety signals from the post-marketing period.",
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      "text": "“seizures and cardiovascular events are of special interest.” — FDA",
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      "text": "Source: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/211150Orig2s000MedR.pdf; https://journals.sagepub.com/doi/full/10.1177/1024907918754921",
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