[{"id":"appr-ep1","name":"% triglyceride reduction at 3 months","type":"PRIMARY","unit":"%","notes":"Placebo-adjusted difference: ~95 percentage points. Absolute mean TG decrease: -1,712 mg/dL in volanesorsen arm.","p_value":"<0.001","results":[{"arm":"appr-vol","label":"-77% reduction","value":-77},{"arm":"appr-pbo","label":"+18% (increase)","value":18}],"timepoint":"Month 3","description":"FCS patients have triglycerides often >2,000 mg/dL (normal is <150). They live with constant risk of life-threatening pancreatitis. Any substantial TG reduction reduces pancreatitis risk dramatically."}]
Thrombocytopenia (platelets <140K): 76% volanesorsen vs 24% placebo. Grade 4 thrombocytopenia (<25K): 6% (2/33). Injection site reactions 79% (mostly mild). 27% (9/33) discontinued due to AEs: 5 for platelet decreases, 4 for other AEs. Protocol amended mid-trial for platelet monitoring every 2 weeks.
NOTE: APPROACH data is for volanesorsen (Waylivra), the first-generation product. Tryngolza (olezarsen) is the next-gen successor with improved safety. The -77% TG reduction validates the apoC-III target; the thrombocytopenia is what olezarsen fixes. Tryngolza approved for FCS based on BALANCE trial with better safety profile.