{ "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": 122, "pageCount": 366, "prevPage": 121, "nextPage": 123, "slideType": "expose_contradiction", "function": "expose_contradiction", "density": "overcrowded", "nDataPoints": 10, "notes": "The slide uses a 'before-after' or 'comparison' logic to expose data manipulation in clinical reporting.", "elementsJson": [ "paragraph", "screenshot" ], "metadataConfidence": 1, "imagePath": null, "slideHref": "/slides/019dd923-622c-750b-8b9a-21918ac10c17/122", "deckHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17", "deckJsonHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17.json", "deckAnchorHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17#slide-122", "components": [ { "bbox": { "h": 0.05, "w": 0.86, "x": 0.07, "y": 0.45 }, "kind": "callout", "text": "Pitolisant label indicates steady state Cmax 78 ng/mL (“range 49.2 ng/mL to 126 ng/mL”).", "attrs": null, "subkind": "primary", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "31b47d35-0b5d-4a4f-afdd-1e8b87b29d8e", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.08, "w": 0.86, "x": 0.07, "y": 0.67 }, "kind": "callout", "text": "2007 pilot study indicates 101 ng/mL with more variability, as well as a significant percentage of patients with levels elevated >150 ng/mL, who were excluded in calculating the average", "attrs": null, "subkind": "primary", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "bccc1b84-99e3-468e-abeb-22817d4c4088", "frameworkName": null, "frameworkSlug": null }, { "bbox": null, "kind": "callout", "text": "This clearly indicates that plasma levels are significantly higher than the range indicated on the label, and that the label is a fiction.", "attrs": null, "subkind": null, "toolName": "Visual emphasis", "toolSlug": "visual-emphasis", "confidence": null, "componentId": "019dd953-64d0-7099-9cd2-654fa3150e1c", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.15, "w": 0.86, "x": 0.07, "y": 0.49 }, "kind": "paragraph", "text": "12.3 Pharmacokinetics Following oral administration of pitolisant 35.6 mg once daily, the steady state Cmax and AUC are 73 ng/mL (range: 49.2 to 126 ng/mL) and 812 ng*hr/mL (range: 518 to 1468 ng*hr/mL), respectively. Pitolisant exposure (Cmax and AUC) increases proportionally with dose and steady state is reached by day 7.", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "8877c566-485e-44e6-aaef-395a81e6fedb", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.15, "w": 0.86, "x": 0.07, "y": 0.07 }, "kind": "paragraph", "text": "Given the lack of typical PK data, the asserted plasma levels are suspicious and exhibit various red flags. For example, the label states that at the max dose of 35.6 mg/day, the mean plasma is 73 ng/mL with a range between 42.9 ng/mL and 126 ng/mL.", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "a261d1c1-d3f5-4116-9362-c57607706b10", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.15, "w": 0.86, "x": 0.07, "y": 0.75 }, "kind": "paragraph", "text": "Tiprolisant dosages were performed at the end of the treatment period with a median sampling time at 3.75 h after the last drug intake. The plasma level average was 100.6±78.1 ng/ml (n=17). Elevated plasma levels (> 150 ng/ml) were observed in 5 patients, in some cases related to the experience of adverse events occurring a few hours after drug intake.", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "b48507f3-d4e4-43b3-b84e-7849763f8303", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.25, "w": 0.86, "x": 0.07, "y": 0.22 }, "kind": "paragraph", "text": "However, the 2007 pilot study indicated it was 101 ng/mL with a standard deviation of 78 ng/mL – 38% higher with a wider rage, despite the dose (40mg) being only 12% higher. Moreover, this pilot indicated 5 of 22 patients had far higher levels “> 150 ng/mL” – and as we noted earlier, the paper cleverly excluded those 5 in calculating the average of 101 ng/mL. This clearly indicates that plasma levels are significantly higher than the range indicated on the label, and that the label is a fiction.", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "c32a393e-6017-4d0b-b8ba-b58431b5e031", "frameworkName": null, "frameworkSlug": null }, { "bbox": null, "kind": "quote", "text": "Elevated plasma levels (> 150 ng/ml) were observed in 5 patients, in some cases related to the experience of adverse events occurring a few hours after drug intake. — 2007 pilot study", "attrs": null, "subkind": null, "toolName": "Authority citation", "toolSlug": "authority-citation", "confidence": null, "componentId": "019dd953-64d0-7099-9cd2-6b48776ae3f6", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.03, "w": 0.7, "x": 0.07, "y": 0.94 }, "kind": "source-note", "text": "Source: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000ClinPharmR.pdf; https://pubmed.ncbi.nlm.nih.gov/18295497/", "attrs": null, "subkind": null, "toolName": null, "toolSlug": null, "confidence": null, "componentId": "7369b713-9b46-4532-959f-256ddaa00b7f", "frameworkName": null, "frameworkSlug": null } ], "metrics": [], "tools": [], "frameworks": [], "arcBeats": [], "loops": [], "imagePathAlt": null, "thumbSrc": null, "thumbSrcAlt": null, "locked": true }