Sanofi (France) and Regeneron Pharmaceuticals, Inc. Announce Publication of Phase 2 Results with LDL Cholesterol-Lowering PCSK9 Antibody in the New England Journal of Medicine
Published: Nov 01, 2012
PARIS and TARRYTOWN, N.Y., Oct. 31, 2012 /PRNewswire/ -- Sanofi (EURONEXT: SAN and NYSE: SNY) and Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that results from a Phase 2 trial of SAR236553/REGN727 in patients with primary hypercholesterolemia were published in the October 31, 2012 issue of the New England Journal of Medicine.
The study enrolled patients with primary hypercholesterolemia with elevated LDL-C (greater than or equal to 100 mg/dL) who were on a stable low dose of atorvastatin (10 mg). The primary objective of the study was to compare the effect on LDL-C lowering of switching to a high dose of atorvastatin alone (80 mg) versus a high dose of atorvastatin combined with SAR236553/REGN727 administered in a 1ml injection every two weeks.
Patients who received SAR236553/REGN727 administered in a 1ml injection every two weeks plus atorvastatin 80 mg achieved a mean reduction of 73% in LDL-C, compared to a mean reduction of 17% for patients who switched to atorvastatin 80 mg alone (p<0.001) after eight weeks. Ninety percent (90%) of patients achieved a pre-specified level of 70mg/dL compared to 17.2% for patients who switched to atorvastatin 80 mg alone (p<0.001).
The study also included a third arm in which SAR236553/REGN727 150mg administered in a 1ml injection every two weeks was added to the stable 10 mg of atorvastatin. Ninety-six percent (96.6%) of patients achieved the pre-specified goal of 70mg/dL in this treatment group.
In this trial, the most common adverse events (AE) reported in patients treated with SAR236553/REGN727 plus atorvastatin were headache, dizziness, and diarrhea. There was one serious AE in the SAR236553/REGN727 plus atorvastatin 80 mg group (dehydration) that was deemed not to be treatment-related.
This study was part of the Phase 2 program of SAR236553/REGN727, an investigational, subcutaneously administered, fully-human antibody targeting PCSK9 (proprotein convertase subtilisin/kexin type 9) that is currently being studied in the ODYSSEY Phase 3 trials for the lowering of low-density lipoprotein cholesterol (LDL-C). Preclinical studies have shown that inhibiting PCSK9 leads to an increase in LDL receptors, which bind to LDL-C and clear it from the blood stream. The publication can be accessed at http://www.nejm.org.
Additionally, new data from the Phase 2 studies of SAR236553/REGN727 will be presented at oral sessions at the American Heart Association's Scientific Sessions 2012 (AHA). Results of these presentations are embargoed until the times listed below. The presentations are:
Embargoed until November 6, 2012 at 9:30 AM PST:
- Effect of SAR236553/REGN727 Fully Human Monoclonal Anti-Proprotein Convertase Subtilisin/Kexin Type 9 Antibody on Plasma Lipoprotein(a) Concentrations: Pooled Analysis from Three Phase 2 Studies. Tuesday, November 6, 2012, 9:30-9:45 AM PST. Presenter: Daniel Gaudet, M.D., Professor of Medicine, University of Montreal. [Abstract No. 14725]
Embargoed until November 6, 2012 at 4:45 PM PST :
- Effect of REGN727/SAR236553 Anti-Proprotein Convertase Subtilisin/Kexin Type 9 Fully Human Monoclonal Antibody in Patients with Elevated Triglycerides/Low High-Density Lipoprotein Cholesterol: Data from Three Phase 2 Studies. Tuesday, November 6, 2012, 4:45-5:00 PM PST. Presenter: Robert Dufour, M.D., M.Sc., Associate Director, Institut de Recherches Cliniques de Montreal. [Abstract No. 16127]
PCSK9 is known to contribute to circulating LDL-C levels, as it binds to LDL receptors resulting in their degradation so that fewer are available on liver cells to remove LDL-C from the blood. Moreover, traditional LDL-lowering therapies such as statins actually stimulate the production of PCSK9, which limits their own ability to lower LDL-C. Inhibiting the PCSK9 pathway is therefore a potentially novel mechanism for lowering LDL-C.
About SAR236553/REGN727 and the Phase 2 Program
SAR236553/REGN727, created using Regeneron's VelocImmune® technology, is a fully human monoclonal antibody directed against PCSK9, administered via subcutaneous injection. By inhibiting PCSK9, a determinant of circulating LDL-C levels in the blood, SAR236553/REGN727 increases the number of free LDL receptors which can clear circulating LDL-C from the bloodstream.
SAR236553/REGN727 has been studied in three Phase 2 clinical studies: Two dose ranging studies in patients with hypercholesterolemia; one with 183-patients, and another with 92-patients, and one study of 77 patients with heterozygous familial hypercholesterolemia (heFH). In the primary hypercholesterolemia trials treatment with different dose regimens of SAR236553/REGN727 on top of statin therapy significantly reduced LDL-C from baseline by 40% to 72% over the 8 or 12-week treatment period. A third Phase 2 study was in patients with heFH whose LDL-C levels remained elevated despite statin therapy with or without ezetimibe. Across the four tested doses of SAR236553/REGN727 administered for up to 12 weeks, patients achieved a mean reduction in LDL-C from baseline of 28% to 68%. In the Phase 2 program, injection site reactions were the most common adverse events with SAR236553/REGN727. Rare cases of hypersensitivity reaction were also reported. There were five serious adverse events (SAE) in the active treatment arms (1.8%, 5/275) and two SAEs in the placebo groups (2.6%, 2/77).
About Regeneron Pharmaceuticals
Regeneron is a fully integrated biopharmaceutical company that discovers, invents, develops, manufactures, and commercializes medicines for the treatment of serious medical conditions. Regeneron markets three products in the United States, EYLEA® (aflibercept) Injection, ZALTRAP® (ziv-aflibercept) Injection for Intravenous Infusion, and ARCALYST® (rilonacept) Injection for Subcutaneous Use; ZALTRAP is co-commercialized with Sanofi. Phase 3 studies are in progress with EYLEA in two additional indications and with product candidates sarilumab and REGN727. Regeneron has active research and development programs in many disease areas, including ophthalmology, inflammation, cancer, and hypercholesterolemia. Additional information and recent news releases are available on the Regeneron web site at www.regeneron.com.
Sanofi, a global and diversified healthcare leader, discovers, develops and distributes therapeutic solutions focused on patients' needs. Sanofi has core strengths in the field of healthcare with seven growth platforms: diabetes solutions, human vaccines, innovative drugs, consumer healthcare, emerging markets, animal health and the new Genzyme. Sanofi is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).
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SOURCE Regeneron Pharmaceuticals, Inc.