{
  "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": 119,
  "pageCount": 366,
  "prevPage": 118,
  "nextPage": 120,
  "slideType": "expose_contradiction",
  "function": "expose_contradiction",
  "density": "dense",
  "nDataPoints": 0,
  "notes": "The slide uses direct quotes from the EMA's CHMP assessment report to highlight regulatory discrepancies.",
  "elementsJson": [
    "paragraph",
    "quote_block",
    "footnote"
  ],
  "metadataConfidence": 1,
  "imagePath": null,
  "slideHref": "/slides/019dd923-622c-750b-8b9a-21918ac10c17/119",
  "deckHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17",
  "deckJsonHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17.json",
  "deckAnchorHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17#slide-119",
  "components": [
    {
      "bbox": null,
      "kind": "callout",
      "text": "The CHMP identified several shortcomings in the documentation provided on the pharmacokinetics of pitolisant.",
      "attrs": null,
      "subkind": null,
      "toolName": "Visual emphasis",
      "toolSlug": "visual-emphasis",
      "confidence": null,
      "componentId": "019dd953-64d0-7099-9cd2-7ce405570192",
      "frameworkName": null,
      "frameworkSlug": null
    },
    {
      "bbox": {
        "h": 0.38,
        "w": 0.86,
        "x": 0.07,
        "y": 0.07
      },
      "kind": "paragraph",
      "text": "The FDA's various pre-approval reviews indicate the agency simply accepted the company's PK claims at face value, despite striking red flags that we shall detail. However, the European Medicines Agency, as part of their review in 2015, exhibited significant concern, noting “shortcomings in the documentation provided on the pharmacokinetics of pitolisant”; “many discrepancies”; “gaps in the understanding of the pharmacokinetics of the drug, introducing uncertainty...in the safety and efficacy...when administered to different subgroups or when co-administered” – “despite further analysis” requested by the EMA; and that PK in elderly patients or those with “renal and hepatic impairment could not be safely predicted.” The EMA therefore requested various PK studies as post-approval measures. We find one sentence particularly striking – that the “gaps include basic pharmacokinetic properties of pitolisant.”",
      "attrs": null,
      "subkind": "paragraph",
      "toolName": null,
      "toolSlug": null,
      "confidence": null,
      "componentId": "8bd5b6f5-0695-4bd2-862c-878397582269",
      "frameworkName": null,
      "frameworkSlug": null
    },
    {
      "bbox": {
        "h": 0.35,
        "w": 0.86,
        "x": 0.07,
        "y": 0.56
      },
      "kind": "paragraph",
      "text": "The CHMP identified several shortcomings in the documentation provided on the pharmacokinetics of pitolisant. There were many discrepancies between the values of PK parameters in the different studies reports. Despite further analysis of the available data provided by the Applicant, there still are gaps in the understanding of the pharmacokinetics of the drug, introducing uncertainty in the assessment of the safety and efficacy of the product when administered to different subgroups or when co-administered with other drugs. These gaps include basic pharmacokinetic properties of pitolisant. Major elimination pathways are insufficiently understood for the drug and require additional investigations. Therefore, the Applicant has been requested to perform a new balance study after repeated dose administration in order to identify the major metabolites and characterize their PK behaviour and the mechanisms underlying their formation. This study will be conducted as a post-approval measure.",
      "attrs": null,
      "subkind": "paragraph",
      "toolName": null,
      "toolSlug": null,
      "confidence": null,
      "componentId": "b45c86a7-b165-435e-85c2-bd2e280bb7c6",
      "frameworkName": null,
      "frameworkSlug": null
    },
    {
      "bbox": null,
      "kind": "quote",
      "text": "“shortcomings in the documentation provided on the pharmacokinetics of pitolisant”; “many discrepancies”; “gaps in the understanding of the pharmacokinetics of the drug, introducing uncertainty...in the safety and efficacy...when administered to different subgroups or when co-administered” — EMA’s Committee for Medicinal Products for Human Use (CHMP)",
      "attrs": null,
      "subkind": null,
      "toolName": "Authority citation",
      "toolSlug": "authority-citation",
      "confidence": null,
      "componentId": "019dd953-64d0-7099-9cd2-8147d4ff64cb",
      "frameworkName": null,
      "frameworkSlug": null
    },
    {
      "bbox": {
        "h": 0.02,
        "w": 0.55,
        "x": 0.07,
        "y": 0.94
      },
      "kind": "source-note",
      "text": "Source: https://www.ema.europa.eu/en/documents/assessment-report/wakix-epar-public-assessment-report_en.pdf",
      "attrs": null,
      "subkind": null,
      "toolName": null,
      "toolSlug": null,
      "confidence": null,
      "componentId": "5cc9617d-439b-4a2e-8c7b-7e4367c81ea6",
      "frameworkName": null,
      "frameworkSlug": null
    },
    {
      "bbox": {
        "h": 0.03,
        "w": 0.55,
        "x": 0.07,
        "y": 0.51
      },
      "kind": "title",
      "text": "Pitolisant review by EMA’s Committee for Medicinal Products for Human Use (CHMP)",
      "attrs": null,
      "subkind": "headline",
      "toolName": null,
      "toolSlug": null,
      "confidence": null,
      "componentId": "e8de205b-2f32-4894-b080-f4b00b985a24",
      "frameworkName": null,
      "frameworkSlug": null
    }
  ],
  "metrics": [],
  "tools": [],
  "frameworks": [],
  "arcBeats": [],
  "loops": [],
  "imagePathAlt": null,
  "thumbSrc": null,
  "thumbSrcAlt": null,
  "locked": true
}