{ "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": 157, "pageCount": 366, "prevPage": 156, "nextPage": 158, "slideType": "appendix_disclosure", "function": "expose_contradiction", "density": "dense", "nDataPoints": 0, "notes": "The slide presents clinical case summaries to address potential safety concerns regarding cardiac events.", "elementsJson": [ "paragraph", "callout_box" ], "metadataConfidence": 1, "imagePath": null, "slideHref": "/slides/019dd923-622c-750b-8b9a-21918ac10c17/157", "deckHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17", "deckJsonHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17.json", "deckAnchorHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17#slide-157", "components": [ { "bbox": null, "kind": "callout", "text": "A reported ICSR of cardiac arrest in a young (49-year-old) female patient is notable given the reports of sudden death in the OSA development program.", "attrs": null, "subkind": null, "toolName": "Visual emphasis", "toolSlug": "visual-emphasis", "confidence": null, "componentId": "019dd953-64d0-7099-9cd7-5ec9e3f13e03", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.18, "w": 0.62, "x": 0.07, "y": 0.33 }, "kind": "paragraph", "text": "FDA comments on cardiac arrest in 49-year old, FDA CDER Clinical Review (Solages, Sep 28, 2020)\nA reported ICSR of cardiac arrest in a young (49-year-old) female patient is notable given the reports of sudden death in the OSA development program. The patient has a medical history that was remarkable for narcolepsy, obesity, diabetes, and hypertension. The duration of exposure to pitolisant is not included in the case report. The patient was also prescribed methylphenidate. Both pitolisant and methylphenidate were discontinued. The patient recovered.", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "5cfdf668-900d-41ae-9e94-7c32ed2e2185", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.41, "w": 0.62, "x": 0.07, "y": 0.53 }, "kind": "paragraph", "text": "...and on 60-year old with dizziness, ischemic attack, and QT prolongation\n(b) (6): 60-year-old female with medical history of narcolepsy, two prior transient ischemic attacks, atherosclerosis, bilateral carotid dysplasia, hypertension, hypercholesterolemia, depression, fibromuscular dysplasia, asthma, thyroid dysfunction, angioedema, cephalalgia, and first-degree atrioventricular block at screening. She experienced sudden onset of dizziness with nausea approximately one month after the first dose of pitolisant. Accompanying symptoms included erratic gate with deviation to the right side, paresthesia of the right hemi-face, malaise, and brief loss of consciousness. Findings on clinical examination included a right carotid murmur and known muscular strength weakness on the right side; clinical examination was otherwise unremarkable. She was given a diagnosis of transient ischemic attack and discharged home on the day of presentation. She was reported to be symptom-free at the time of discharge. She continued to receive pitolisant 40 mg once daily and completed the study. Other adverse events reported during the study by this patient included prolonged QTc, nonspecific polarization abnormality, pericarditis, increased serum GGT, headache, depression, bronchitis, otitis, increased weight, and cataplexy.\nReviewer comment: This patient had a prior history of TIA and significant risk factors for TIA and stroke. The TIA resolved, and the patient was able to complete the study. No clear temporal relationship between pitolisant treatment and the onset of the adverse event is evident, although a correlation between TIA and pitolisant cannot be definitively established or ruled out based on this single case.", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "67045ba8-8786-419c-89c8-7e65eb62d32a", "frameworkName": null, "frameworkSlug": null }, { "bbox": null, "kind": "quote", "text": "“notable given reports of sudden death” — FDA CDER Clinical Review (Solages, Sep 28, 2020)", "attrs": null, "subkind": null, "toolName": "Authority citation", "toolSlug": "authority-citation", "confidence": null, "componentId": "019dd953-64d0-7099-9cd7-632cd941870b", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.03, "w": 0.45, "x": 0.07, "y": 0.95 }, "kind": "source-note", "text": "Source: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/211150Orig2s000MedR.pdf", "attrs": null, "subkind": null, "toolName": null, "toolSlug": null, "confidence": null, "componentId": "9b2f809e-d7ca-4134-a4bd-bd38bd0caaed", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.22, "w": 0.86, "x": 0.07, "y": 0.07 }, "kind": "title", "text": "The FDA also discussed two non-fatal cardiac events: 1) a cardiac arrest in a 49-year old female, based on a European post-marketing Serious Individual Case Safety Report, where duration of pitolisant exposure wasn’t available but which was “notable given reports of sudden death” in the pitolisant sleep apnea trials; and 2) a 60-year old female with dizziness one month after starting pitolisant, transient ischemic attack, and QT prolongation, where the FDA reviewed stated a correlation with pitolisant “cannot be definitively established or ruled out.”", "attrs": null, "subkind": "headline", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "3ebc38fc-4168-492f-adc1-bd9ceef13f26", "frameworkName": null, "frameworkSlug": null } ], "metrics": [], "tools": [], "frameworks": [], "arcBeats": [], "loops": [], "imagePathAlt": null, "thumbSrc": null, "thumbSrcAlt": null, "locked": true }