ODYSSEY OLE ( open-label extension ) has included patients diagnosed with heterozygous familial hypercholesterolemia ( HeFH ), receiving maximally tolerated statins, who had completed one of four phase 3 double-blind parent studies ( all 18 months' duration ), with the aim to assess longer-term safety and efficacy of Alirocumab ( Praluent ).
Patients received starting dose Alirocumab 75 mg every 2 weeks ( Q2W; patients from FH I, FH II, and LONG TERM ) or Alirocumab 150 mg Q2W ( patients from HIGH FH ).
Low-density lipoprotein cholesterol ( LDL-C ) levels were blinded to the patient and physician until Week 8; from Week 8, LDL-C levels were communicated to physicians.
From Week 12, dose adjustment from 75 to 150 mg Q2W, or vice versa, was possible per physician's clinical judgment according to patient's LDL-C levels.
Patients who had received Alirocumab ( n = 655 ) compared with placebo ( n = 330 ) in the parent studies exhibited similar rates of treatment-emergent adverse events ( TEAEs; 87.3% vs. 83.9% ) during OLE ( 2.5 years median Alirocumab exposure ).
Overall, 33 patients ( 3.4% ) experienced TEAEs leading to permanent treatment discontinuation.
At Week 8, Alirocumab has reduced mean LDL-C by 44.2% ( reduction from 151.9 mg/dL at parent study baseline to 84.9 mg/dL ); reduction in LDL-C was consistent to Week 96 of OLE.
Reductions in lipid parameters were similar regardless of treatment allocation in the parent study.
In conclusion, in patients with HeFH, no unexpected long-term safety concerns were observed with Alirocumab compared with previously published data; durability of LDL-C-lowering over 3 years ( including 1.5 years of parent trials ) was demonstrated. ( Xagena )
Farnier M et al, Atherosclerosis 2018; 278: 307-314