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One prediction that ODYSSEY outcome will fail in primary analysis for primary end-point (15% relative reduction in MACE)???
While, he has good point on low (<100 mg/dL) entry-level for LDLc, he did neglected that it is after high-intensity statins run-in period of 4-24 w (average ~16 w to stabilize LDLc level). So, at randomization time point, PCSK9 level is elevated (in part due to high intensity statins), as well as Lpa (second important lipid marker for CVD high risk). On those two bio-markers (also Apob on total triglycerides) PCSK9 Abs have significant lowering effects.
Second, MACE event rate in Odyssey trial are somehow reduced than initially expected/projected...indicating better (diet, SOC,...) management of comorbidity factors and better overall health. This, in overall, may reduce anti-PCSK9 Abs capacity to show health benefit. However, longer treatment duration (with ups and downs in placebo arm) my bring needed difference.
Failure in interim analysis is sticky point. One explanation is that after Repatha no mortality benefit in Furier, REGN amended interim analysis with strong mortality benefit (in addition to 18% RR in primary). I would do this (to give better chance marketing efforts), but I may be way to optimistic in regards what REGN did at interim.
I would think that there is significant %-tage of the "street population" that expect dismal and/or non-significant CVOT results. |
