Sanofi and Regeneron Pharmaceuticals are moving a novel cholesterol treatment into Phase III trials in the next few weeks following the publication of full mid-stage data.
The drug in question, SAR236553/REGN727, is a subcutaneous fully-human antibody targeting PCSK9 (proprotein convertase subtilisin/kexin type 9) for patients with heterozygous familial hypercholesterolaemia (heFH). The full set of data, which were presented at the European Atherosclerosis Society Congress in Milan, follow positive top-line results announced in November.
The trial randomised 77 patients with heFH whose low-density lipoprotein-cholesterol (LDL-C) levels remained uncontrolled on statin therapy with or without Merck & Co's Vytorin (ezetimibe). Across the four doses tested, patients receiving SAR236553 for 12 weeks achieved a mean LDL-C reduction of 28.9% to 67.9%, compared to 10.7% in those on placebo. For the 150 mg (every two weeks), 93.8% of patients achieved LDL-C levels lower than 100 mg/dL compared to 13.3% of patients on placebo, and 81.3% reached LDL-C levels lower than 70 mg/dL compared to none on placebo.
Based on the results and following discussions with the US and European regulatory authorities, Sanofi and Regeneron intend to initiate a global Phase III programme in June. They will be the first late-stage studies of an investigational drug targeting PCSK9 and the French drugmaker noted that statins actually stimulate the production of PCSK9, which limits their own ability to lower LDL-C.
The companies quoted Evan Stein, director of the Metabolic and Atherosclerosis Research Center in Cincinnati and principal investigator of the study, as saying that heFH is "a common, serious, and often undiagnosed cause of early heart disease [and] there remains a high degree of unmet need in these patients". He added that these data suggest that SAR236553 / REGN727 "may provide a new option, on top of existing therapies, to lower LDL-cholesterol".