More positive data on effectiveness of novel monoclonal antibody

New phase 2 data demonstrate substantial reductions in LDL when patients with heterozygous familial hypercholesterolemia were administered REGN727/SAR236553, a fully human monoclonal antibody directed against proprotein convertase subtilisin/kexin type 9 serine protease, or PCSK9.

The randomized, double blind, placebo-controlled, dose-finding study included 77 patients with heterozygous familial hypercholesterolemia. The patients’ LDL levels remained uncontrolled (≥100 mg/dL) on statin therapy, with or without ezetimibe. Patients were assigned to placebo or one of four active dose regimens of REGN727/SAR236553 (REGN727; Sanofi/Regeneron): 150 mg at 4-week intervals; 200 mg at 4-week intervals; 300 mg at 4-week intervals; or 150 mg at 2-week intervals. All patients were followed for 20 weeks for safety.

The primary endpoint was change in LDL from baseline to 12 weeks. Across the four dosing regimens tested, patients assigned REGN727 for 12 weeks achieved a mean LDL reduction from baseline of 28.9% to 67.9% compared with 10.6% in patients assigned placebo (P<.05 for all dose groups). In addition, in the most intense dose regimen tested in which the greatest LDL reduction was observed (150 mg every 2 weeks), 93.8% of patients achieved LDL levels <100 mg/dL vs. 13.3% of patients assigned placebo, and 81.3% achieved LDL levels <70 mg/dL vs. none on placebo, according to a press release.

Therapy was well tolerated in this patient population. One serious adverse event was reported in the placebo group and none were reported in the REGN727 group. Additionally, there were no elevations in liver function tests more than three times the upper limit of normal, and no cases of elevated creatinine kinase were reported. The most common adverse event was injection-site reaction.

“There remains a high degree of unmet need in these patients [with heterozygous familial hypercholesterolemia], as a large percentage are unable to reach optimal LDL goals despite being on maximal lipid-lowering therapy. These data suggest that SAR236553/REGN727 may provide a new option, on top of existing therapies, to lower LDL and finally reach LDL goals for these difficult-to-treat patients,” Evan A. Stein, MD, PhD, director of the Metabolic and Atherosclerosis Research Center in Cincinnati, said in the release.

The phase 2 trial was conducted at 16 lipid clinics in the United States and Canada.

Results were published online in The Lancet and were also presented during a late-breaking clinical trials session at the 80th European Atherosclerosis Society Congress in Milan, Italy. Other positive data were presented at the American College of Cardiology 61st Scientific Sessions in March.

The companies also announced the initiation of a global phase 3 program with SAR236553/REGN727 in June, according to the release.

For more information:

Stein EA. Lancet. 2012;doi:10.1016/S0140-6736(12)60771-5.

Stein EA. Abstract #1398. Presented at: the 80th European Atherosclerosis Society Congress; May 25-28, 2012; Milan, Italy.

Disclosure: The study was funded by Sanofi and Regeneron.