{ "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": 245, "pageCount": 366, "prevPage": 244, "nextPage": 246, "slideType": "expose_contradiction", "function": "expose_contradiction", "density": "dense", "nDataPoints": 12, "notes": "The slide uses red text and boxes to emphasize the contradiction between the trial paper's claims and the EMA's findings.", "elementsJson": [ "paragraph", "callout_box" ], "metadataConfidence": 1, "imagePath": null, "slideHref": "/slides/019dd923-622c-750b-8b9a-21918ac10c17/245", "deckHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17", "deckJsonHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17.json", "deckAnchorHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17#slide-245", "components": [ { "bbox": { "h": 0.06, "w": 0.86, "x": 0.07, "y": 0.61 }, "kind": "callout", "text": "EMA review (Annex 1) indicated massive discontinuation rates, and indicated 12-mo ESS reduction lower than that purported in HARMONY 3 trial paper and no different than placebo reduction in prior trials", "attrs": null, "subkind": "primary", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "a24b2435-ed2f-4c91-9b49-49f358e51b03", "frameworkName": null, "frameworkSlug": null }, { "bbox": null, "kind": "metric", "text": "ESS score reduction: -3.62", "attrs": null, "subkind": "primary", "toolName": "Quantification", "toolSlug": "quantification", "confidence": null, "componentId": "019dd953-64d1-73a9-abba-06352acfde64", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.25, "w": 0.86, "x": 0.07, "y": 0.68 }, "kind": "paragraph", "text": "The open-label, long-term Phase III study (HARMONY III) assessed the long term safety of pitolisant in patients suffering from narcolepsy (with or without cataplexy) over 12 months and with an extension of up to 5 years. 102 narcoleptic patients with or without cataplexy were included in the 12 months follow-up period. 68 patients completed the first 12 months period. 45, 38, 34 and 14 patients completed the 2, 3, 4 and 5 year follow-up periods, respectively. The maximal dose received during the study was 36 mg / day in 85% of patients. After 12 months of treatment, improvements in EDS assessed by ESS score of remaining patients is of same magnitude as those observed in the other trials in narcoleptic patients. The decrease in mean ESS score (SD) was -3.62 (4.63) after 1 year. ESS score reduction lower than -4.6 in trial paper (excerpted in previous slide)", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "73547c51-6d64-40ea-8eb5-f0ac3535746c", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.35, "w": 0.86, "x": 0.07, "y": 0.2 }, "kind": "paragraph", "text": "HARMONY 3 calls into question the purported ESS reductions in the three principal trials in support of the pitolisant NDA (HARMONY 1, 1-bis, and CTP), as it was an open-label trial with a low bar given the subjective patient-reported ESS questionnaire, yet the ESS reductions were markedly lower than in the pivotal studies. A nugget buried in an appendix of the EMA review is even more damning, as it shows that most patients discontinue the drug. The HARMONY 3 paper states that 40% of de novo patients discontinued within months due to lack of efficacy. Data provided to the EMA – which the FDA never mentions – indicates the discontinuations only accelerate after year one. HARMONY 3 followed patients for 5 years, even though the trial paper (2019) fails to disclose this fact, and nor does it show any data beyond the first year, which we find troubling. The EMA states that of 102 patients at the start of HARMONY 3, 68 (67%) were left at 12 months, and only 44%, 37%, 33%, and 14% at years 2, 3, 4, and 5. The ESS score at the end of year 1 is even lower than that claimed in the trial paper (-3.62 vs. -4.6) – a reduction identical to that in the placebo arm in their previous trials.", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "f7f9ac67-b53b-4ef8-88d8-8cff576a6310", "frameworkName": null, "frameworkSlug": null }, { "bbox": null, "kind": "quote", "text": "The ESS score at the end of year 1 is even lower than that claimed in the trial paper (-3.62 vs. -4.6) – a reduction identical to that in the placebo arm in their previous trials.", "attrs": null, "subkind": null, "toolName": "Authority citation", "toolSlug": "authority-citation", "confidence": null, "componentId": "019dd953-64d1-73a9-abba-0355ea0a2074", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.02, "w": 0.4, "x": 0.07, "y": 0.95 }, "kind": "source-note", "text": "Source: https://www.ema.europa.eu/en/documents/product-information/wakix-epar-product-information_en.pdf", "attrs": null, "subkind": null, "toolName": null, "toolSlug": null, "confidence": null, "componentId": "03a292f9-21fb-4d4d-8f62-855a1e8455fb", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.12, "w": 0.86, "x": 0.07, "y": 0.07 }, "kind": "title", "text": "HARMONY 3 calls into question the purported ESS reductions in the three principal trials in support of the pitolisant NDA", "attrs": null, "subkind": "headline", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "6531789a-0126-44d1-865d-714d50734a4f", "frameworkName": null, "frameworkSlug": null } ], "metrics": [], "tools": [], "frameworks": [ { "name": "fraud-exposure", "slug": null, "matchId": "a26ad4f8-555a-4609-9388-e87baeaac34d", "evidence": "Exposing discrepancies between trial paper claims and EMA review data.", "confidence": 0.9 } ], "arcBeats": [], "loops": [], "imagePathAlt": null, "thumbSrc": null, "thumbSrcAlt": null, "locked": true }