New England Journal of Medicine Publishes Positive Detailed Results From Praluent® (alirocumab) Injection Cardiovascular Outcomes Trial
TARRYTOWN, N.Y. and PARIS, Nov. 7, 2018 /PRNewswire/ --
Praluent significantly reduced major adverse cardiovascular events by 15% (p<0.001)
Praluent was associated with a 15% lower risk of death from any cause (hazard ratio [HR] 0.85; 95% confidence interval [CI], 0.73 to 0.98)1
Additional analyses, including mortality, to be presented at upcoming American Heart Association Scientific Sessions, November 10-12
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced that the New England Journal of Medicine (NEJM) has published positive detailed results of the 18,924-patient ODYSSEY OUTCOMES trial.
The trial met its primary endpoint, showing that Praluent® (alirocumab) Injection significantly reduced the risk of major adverse cardiovascular events (MACE) in patients who had suffered an acute coronary syndrome (ACS), which included a heart attack or unstable angina. MACE occurred in 903 patients (9.5%) in the Praluent group and in 1,052 patients (11.1%) in the placebo group (HR 0.85; 95% CI, 0.78 to 0.93; p<0.001).
Death from any cause was less frequent among Praluent-treated patients. Praluent was associated with a 15% lower risk of death; death occurred in 334 (3.5%) patients in the Praluent group and 392 (4.1%) patients in the placebo group (HR 0.85; 95% CI, 0.73 to 0.98).1
The NEJM publication also includes results for MACE and other secondary endpoints including death, according to subgroups of baseline LDL-C (low-density lipoprotein cholesterol) levels, which are described in detail in the Supplementary Appendix. The data showed that patients with higher LDL-C at baseline (at least 100 mg/dL) were at greater risk of MACE, as well as other secondary endpoints, including death. Moreover, the greater risk-reduction occurred in this category of patients: in the Praluent group MACE was reduced by 24% (HR 0.76; 95% CI, 0.65 to 0.87) and death from any cause was 29% lower (HR 0.71; 95% CI, 0.56 to 0.90) compared to placebo.2
Adverse events were similar between groups, except for injection site reactions (Praluent 3.8%, placebo 2.1%).
Results of the ODYSSEY OUTCOMES trial were presented at the American College of Cardiology's 67th Annual Scientific Session & Expo in March 2018. Additional analyses, including of mortality, will be presented later this week at the American Heart Association Scientific Sessions 2018.
"Despite the use of statins, many patients with coronary heart disease go on to have recurrent cardiovascular events, underscoring the need for additional treatment options. This need is particularly urgent among patients with acute coronary syndrome and LDL-C levels that remain high, despite best possible application of statin therapy," said Dr. Gregory G. Schwartz, M.D., Ph.D., University of Colorado School of Medicine, Aurora, CO, and co-chair of the trial. "These data in the New England Journal of Medicine show that adding alirocumab to intensive or maximum tolerated statin treatment significantly reduced the risk of future cardiovascular events. This benefit was heightened among study patients with higher LDL-C levels at baseline."
The effect of Praluent on cardiovascular morbidity and mortality is currently being reviewed by regulatory authorities and has not yet been fully evaluated. Data from the ODYSSEY OUTCOMES trial has been submitted to regulatory authorities in the European Union and in the U.S., where the target action date for the Food and Drug Administration (FDA) decision is April 28, 2019.
ODYSSEY OUTCOMES Trial Design
ODYSSEY OUTCOMES (n=18,924) assessed the effect of Praluent on the occurrence of MACE in patients who had experienced an ACS between 1-12 months (median 2.6 months) before enrolling in the trial, and who were already on intensive or maximally-tolerated statin treatment. Patients were randomized to receive Praluent (n=9,462) or placebo (n=9,462) and were assessed for a median of 2.8 years, with some patients being treated for up to five years. Approximately 90% of patients were on a high-intensity statin.
MACE, the primary endpoint, was a composite of death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization.
The trial was designed to maintain patients' LDL-C levels between 25-50 mg/dL, using two different doses of Praluent (75 mg and 150 mg). Praluent-treated patients started the trial on 75 mg every 2 weeks and switched to 150 mg every 2 weeks if their LDL-C levels remained above 50 mg/dL (n=2,615). Some patients who switched to 150 mg switched back to 75 mg if their LDL-C fell below 25 mg/dL (n=805), and patients who experienced two consecutive LDL-C measurements below 15 mg/dL while on the 75 mg dose (n=730) stopped active Praluent therapy for the remainder of the trial.
Praluent inhibits the binding of PCSK9 (proprotein convertase subtilisin/kexin type 9) to the LDL receptor and thereby increases the number of available LDL receptors on the surface of liver cells to clear LDL, which lowers LDL-C levels in the blood. Praluent is being developed by Regeneron and Sanofi under a global collaboration agreement and was invented by Regeneron using the company's proprietary VelocImmune® technology that yields optimized fully-human monoclonal antibodies.
Praluent is approved in more than 60 countries worldwide, including the U.S., Japan, Canada, Switzerland, Mexico and Brazil, as well as the European Union (EU). In the U.S., Praluent is approved for use as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of LDL-C. The effect of Praluent on cardiovascular morbidity and mortality has not been determined.
Important Safety Information for the U.S.
Do not use Praluent if you are allergic to alirocumab or to any of the ingredients in Praluent.
Before you start using Praluent, tell your healthcare provider about all your medical conditions, including allergies, and if you are pregnant or plan to become pregnant or if you are breastfeeding or plan to breastfeed.
Tell your healthcare provider or pharmacist about any prescription and over-the-counter medicines you are taking or plan to take, including natural or herbal remedies.
Praluent can cause serious side effects, including allergic reactions that can be severe and require treatment in a hospital. Call your healthcare provider or go to the nearest hospital emergency room right away if you have any symptoms of an allergic reaction including a severe rash, redness, severe itching, a swollen face, or trouble breathing.
The most common side effects of Praluent include: redness, itching, swelling, or pain/tenderness at the injection site, symptoms of the common cold, and flu or flu-like symptoms. Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
Talk to your doctor about the right way to prepare and give yourself a Praluent injection and follow the "Instructions for Use" that comes with Praluent.
You are encouraged to report negative side effects of prescription drugs to the FDA.
Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
Please click here for the full Prescribing Information.
(1) Analyses for the death endpoints in the overall study fell outside of the statistical hierarchy; and in accordance with recently-implemented NEJM policies, the hazard ratio (HR) and its confidence interval (CI) were published, but no P-values were reported.
(2) Analyses of the death endpoint based on baseline LDL-C levels was not included in the statistical hierarchy; and in accordance with recently-implemented NEJM policies, the hazard ratio (HR) and its confidence interval (CI) were published, but no P-values were reported.
About Regeneron Pharmaceuticals, Inc.
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents life-transforming medicines for people with serious diseases. Founded and led for 30 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to seven FDA-approved treatments and numerous product candidates in development, all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, neuromuscular diseases, infectious diseases and rare diseases.
Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite® technologies, such as VelocImmune® which produces optimized fully-human antibodies, and ambitious research initiatives such as the Regeneron Genetics Center, which is conducting one of the largest genetics sequencing efforts in the world.
For additional information about the company, please visit www.regeneron.com or follow @Regeneron on Twitter.
Sanofi is dedicated to supporting people through their health challenges. We are a global biopharmaceutical company focused on human health. We prevent illness with vaccines, provide innovative treatments to fight pain and ease suffering. We stand by the few who suffer from rare diseases and the millions with long-term chronic conditions.
With more than 100,000 people in 100 countries, Sanofi is transforming scientific innovation into healthcare solutions around the globe.
Sanofi, Empowering Life
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This press release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. ("Regeneron" or the "Company"), and actual events or results may differ materially from these forward-looking statements. Words such as "anticipate," "expect," "intend," "plan," "believe," "seek," "estimate," variations of such words, and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. 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SOURCE Regeneron Pharmaceuticals, Inc.