{ "docId": "019dd923-622c-750b-8b9a-21918ac10c17", "docSlug": "f3db2294dcf9", "documentTitle": "Harmony Biosciences (HRMY)", "authorId": "58_Scorpion_Capital", "authorName": "Scorpion Capital", "documentKindSlug": "research-note", "documentKindLabel": "Research note", "sourceTypeSlug": "short_seller", "sourceTypeLabel": "Short seller", "presentationDate": "2023-03-28 00:00:00", "orientation": "landscape", "aspectRatio": 1.3333334, "pageNumber": 108, "pageCount": 366, "prevPage": 107, "nextPage": 109, "slideType": "expose_contradiction", "function": "expose_contradiction", "density": "dense", "nDataPoints": 4, "notes": "The slide uses a direct quote from a study to argue that 'malaise sensation' is a euphemism for 'fainting' (syncope) to downplay cardiotoxicity.", "elementsJson": [ "paragraph", "screenshot" ], "metadataConfidence": 1, "imagePath": null, "slideHref": "/slides/019dd923-622c-750b-8b9a-21918ac10c17/108", "deckHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17", "deckJsonHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17.json", "deckAnchorHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17#slide-108", "components": [ { "bbox": { "h": 0.03, "w": 0.86, "x": 0.07, "y": 0.51 }, "kind": "callout", "text": "Pitolisant pilot study, first published in 2007, indicates high prevalence of significant adverse events", "attrs": null, "subkind": "primary", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "08bbb67c-3491-4570-8f13-40001b11ccce", "frameworkName": null, "frameworkSlug": null }, { "bbox": null, "kind": "callout", "text": "Two patients with fainting across 22 total suggests an extreme cardiotoxicity signal.", "attrs": null, "subkind": null, "toolName": "Visual emphasis", "toolSlug": "visual-emphasis", "confidence": null, "componentId": "019dd953-64d0-7099-9cd1-79464e709649", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.28, "w": 0.86, "x": 0.07, "y": 0.19 }, "kind": "paragraph", "text": "Given elevated and variable plasma levels, it’s not surprising the study noted seven severe adverse events across 22 pitolisant patients (32%) – using a dose similar to that on the current pitolisant label – with “six of them likely or very likely related to the tiprolisant treatment.” Near the end of the paper, it mentions “fainting sensation” as among the most severe adverse events. Tellingly, the distribution of severe adverse events listed in the relevant paragraph doesn’t mention fainting at all, but includes a vague category called “malaise sensation (n=2)” which we presume is an attempt to downplay the fainting – as fainting sensation (known as syncope) is well-established as the most common symptom of QT prolongation. Two patients with fainting across 22 total suggests an extreme cardiotoxicity signal.", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "5a9e3925-1af6-42e2-974d-0563ea117562", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.35, "w": 0.86, "x": 0.07, "y": 0.56 }, "kind": "paragraph", "text": "first 3 days of treatment. Seven adverse events rated severe occurred in 6 patients during tiprolisant period (and two under the placebo period), six of them likely or very likely related to the tiprolisant treatment, i.e. insomnia (n=2), malaise sensation (n=2), nausea (n=1) and hallucination (n=1). None of these adverse events led to treatment cessation and 21/22 patients fully complied with the prescribed treatments. However, one patient reduced the dosage of tiprolisant from 40 mg/day to 10 mg/day because of adverse events such as mild auditory hallucinations without hypnagogic or hypnopompic characteristics, insomnia and malaise, which then disappeared with the dose reduction and another patient stopped the treatment the day before the exit visit with the investigator. Finally, there were no differences among placebo and period (31.8%). The most frequent adverse events were headache, nausea, insomnia, experienced mainly during the first 3 days of treatment. The most severe adverse events, i.e. insomnia and fainting sensation, probably related to an overdose of tiprolisant, given here in fixed dosage, could be substantially reduced, in future studies, by using an individual titration regimen and starting with a low dose of the drug.", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "8cb77b99-074f-4cb6-b8b0-0765b9a7315d", "frameworkName": null, "frameworkSlug": null }, { "bbox": null, "kind": "quote", "text": "six of them likely or very likely related to the tiprolisant treatment. — Pilot study (2007)", "attrs": null, "subkind": null, "toolName": "Authority citation", "toolSlug": "authority-citation", "confidence": null, "componentId": "019dd953-64d0-7099-9cd1-7e79af7e6a30", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.02, "w": 0.25, "x": 0.07, "y": 0.95 }, "kind": "source-note", "text": "Source: https://pubmed.ncbi.nlm.nih.gov/18295497/", "attrs": null, "subkind": null, "toolName": null, "toolSlug": null, "confidence": null, "componentId": "84781306-654c-4c8c-8db1-c4c25acea8ab", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.12, "w": 0.86, "x": 0.07, "y": 0.07 }, "kind": "title", "text": "The pilot study further contains a buried sentence that suggests an alarming risk of QT prolongation - as well as an attempt to conceal it.", "attrs": null, "subkind": "headline", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "8c99de29-aee4-4ed1-bd3b-ff27228b6fdb", "frameworkName": null, "frameworkSlug": null } ], "metrics": [], "tools": [], "frameworks": [ { "name": "fraud-exposure", "slug": null, "matchId": "7b66b211-4c80-47c5-87a2-4249b7655cda", "evidence": "The slide explicitly claims an attempt to conceal adverse events by using vague terminology.", "confidence": 0.9 } ], "arcBeats": [], "loops": [], "imagePathAlt": null, "thumbSrc": null, "thumbSrcAlt": null, "locked": true }