Sanofi and Regeneron Pharmaceuticals have announced additional positive results from a phase 2 trial of SAR236553/REGN727 in patients with heterozygous familial hypercholesterolemia (heFH). SAR236553/REGN727 is a subcutaneously administered, fully-human antibody targeting PCSK9 (proprotein convertase subtilisin/kexin type 9) in clinical development.
The results from this study were published ahead of print in The Lancet, on 26 May, and also presented at a late-breaking oral session at the 80th European Atherosclerosis Society Congress (EAS) in Milan, Italy, (25–28 May). Positive, top-line results from this study were announced in November 2011.
The trial randomized 77 patients with heFH whose LDL-cholesterol (LDL-C) levels remained uncontrolled on statin therapy with or without ezetimibe. Across the four different dosing regimens tested, patients receiving SAR236553/REGN727 for 12 weeks achieved a mean LDL-C reduction from baseline of 28.9% to 67.9%, compared to 10.7% in patients receiving placebo (p<0.05). In addition, in the most intense dose regimen tested where the greatest LDL-C reduction was observed (150 milligrams [mg] every two weeks), 93.8% of patients achieved LDL-C levels lower than 100 mg/dL (2.59 mmol/L), compared to 13.3% of patients on placebo, and 81.3% reached LDL-C levels lower than 70 mg/dL (1.81 mmol/L), compared to none on placebo.
There were no serious adverse events (SAE) on active treatment, while a single SAE was recorded for a patient in the placebo group. There were no elevations in liver function tests (LFT) >3 times the upper limit of normal (ULN) and no cases of elevated creatinine kinase (CK) were reported. The most common adverse event reported was injection-site reaction.
“Heterozygous familial hypercholesterolemia is a common, serious, and often undiagnosed cause of early heart disease. There remains a high degree of unmet need in these patients as a large percentage are unable to reach optimal LDL-C goals despite being on maximal lipid-lowering therapy,” said Evan A Stein, director of the Metabolic and Atherosclerosis Research Center in Cincinnati, Ohio, and principal investigator of the study. “These data suggest that SAR236553/REGN727 may provide a new option, on top of existing therapies, to lower LDL-cholesterol and finally reach LDL-C goals for these difficult-to-treat patients.”
Sanofi and Regeneron also announced that based on discussions with the US and European regulatory authorities, they intend to initiate a global phase 3 programme with SAR236553/REGN727 in June. This will be the first phase 3 programme of an investigational drug targeting PCSK9.
“These data, along with recently presented data in patients with hypercholesterolemia, further support our belief that blocking PCSK9 with our antibody has the potential to offer a novel mechanism for lowering LDL-cholesterol in a broad range of patients,” said George D Yancopoulos, chief scientific officer, Regeneron and president, Regeneron Laboratories.
“Our global phase 3 programme will include patients with high unmet medical need, such as patients with familial hypercholesterolemia or with elevated cardiovascular risk who cannot reach their LDL-cholesterol goals with current standard therapies. The programme reflects our excitement and commitment to develop this potential therapeutic option for these patients,” said Elias Zerhouni, president, Global Research & Development, Sanofi.