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  "docSlug": "b8afd3741673",
  "documentTitle": "Chinook Therapeutics Inc (KDNY)",
  "authorId": "51_Muddy_Waters",
  "authorName": "Carson C. Block",
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  "presentationDate": "2023-05-16 00:00:00",
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  "notes": "This slide serves as a critical analysis of clinical trial integrity, specifically focusing on the SONAR trial and subsequent reporting practices.",
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      "text": "Both AbbVie and Chinook appear to have manipulated facts and figures to conceal dangers associated with atrasentan.",
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      "text": "in the atrasentan group than in the placebo group.14,15,16 SONAR data reflects an increase in brain natriuretic peptide in patients treated with atrasentan in SONAR. BNP was normal for all patients entering treatment, but quickly became elevated in atrasentan patients.17 Atrasentan is also associated with a statistically-significantly elevated rate of anemia.18 Anemia is a serious risk factor for disease progression in IgAN, an important patient population for Chinook.19,20,21 Reported mortality on atrasentan was numerically higher than reported mortality on placebo in the double-blind period of the SONAR trial.22 This mortality increase in the atrasentan group is also present in the enrichment period.23 Avosentan, a drug with a similar mechanism to atrasentan, had a clinical trial abruptly stopped because of an increased risk of heart failure.24 Studies done on atrasentan and similar drugs show that they raise heart failure risk.25 A sum of cardiac events from the FDA reported adverse effects gives 136 heart failure events on atrasentan and 93 on placebo.26 A very small study using an arguably superior biomarker, inulin, to measure GFR, found that atrasentan seemingly made GFR worse.27 As discussed infra, sparsentan, which has exclusive orphan drug approval for reducing proteinuria in IgAN, is likely safer, showing a less alarming effect on heart failure and anemia.28",
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      "text": "Both AbbVie and Chinook appear to have manipulated facts and figures to conceal dangers associated with atrasentan. AbbVie appears to have manipulated graphs to modify the apparent effect of atrasentan by visually distorting enrichment and post-treatment periods, thereby modifying the slope of the drug effect.29 AbbVie used composite endpoints in its data that conflated positive and negative outcomes from atrasentan, which runs contrary to best clinical practice.30 The SONAR authors then label these endpoints in a misleading way and include questionable endpoints in composites, including non-fatal stroke figures that entirely reverse the meaning of critical endpoints.31 Chinook appears to have misled investors about the number of patients in which atrasentan was trialed, likely to give a false impression of drug safety.32 Chinook has also misrepresented atrasentan's safety profile by claiming no SAEs associated with",
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      "text": "14-32: Citations and references to clinical trial documents and external studies.",
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