Investigational Drug Shows Promise in Hypercholesterolemia

Sanofi and Regeneron recently announced that their investigational hypercholesterolemia drug, alirocumab, met its primary efficacy endpoints in a pair of late-stage trials.

The studies, which were the first phase 3 trials to assess the efficacy and safety of alirocumab administered every 4 weeks, compared the reduction from baseline in low-density lipoprotein cholesterol (LDL-C) at 24 weeks with alirocumab versus placebo in hypercholesterolemia patients.

The first trial, Odyssey Choice I, compared alirocumab 300 mg taken every 4 weeks with placebo in 803 hypercholesterolemia patients with moderate to high cardiovascular (CV) risk. The second trial, Odyssey Choice II, compared alirocumab 150 mg given every 4 weeks with placebo in 233 hypercholesterolemia patients with high CV risk and/or a history of intolerance to 2 or more statins.

More than 68% of patients who enrolled in the first trial were also treated with statins, while none of the second trial’s participants received statin therapy. In both trials, alirocumab-treated patients who did not achieve their pre-specified LDL-C goals or at least a 30% reduction in their LDL-C levels from baseline were switched to alirocumab 150 mg every 2 weeks at 12 weeks.

“In the new monthly dosing trials, Odyssey Choice I and Choice II, the mean percent reduction in LDL-C from baseline was consistent with that seen in previous phase 3 trials evaluating alirocumab every other week dosing,” said Regeneron Vice President Bill Sasiela, PhD, in a press release. “These results continue to validate our clinical development approach, which is designed to investigate various alirocumab doses and intervals to address patients’ lipid-lowering needs.”

The most common adverse events experienced by the trials’ participants were injection site reactions, headache, upper respiratory tract infection, arthralgia, nausea, sinusitis, pain in extremity, and fatigue. Alirocumab-treated patients experienced injection site reactions more frequently than those in the placebo group.

The monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) continues to undergo clinical development; to date, no regulatory agency has evaluated alirocumab’s safety and efficacy.

“Despite current lipid-lowering therapies, many patients at high CV risk struggle to reach optimal LDL-C levels,” said Jay Edelberg, MD, PhD, head of Sanofi’s PCSK9 Development & Launch Unit. “The Odyssey clinical trial program has provided key insights and allowed us to investigate alirocumab administered every four weeks in different patient populations, including those who cannot get control of their high LDL-C because of difficulty tolerating statin therapy.”