Sanofi and Regeneron Announce New Results from Six Phase 3 Trials Showing that Alirocumab Significantly Reduced LDL Cholesterol

PARIS AND TARRYTOWN, N.Y., Nov. 19, 2014 /PRNewswire/ -- Sanofi and Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced new detailed positive results from six Phase 3 ODYSSEY trials that showed alirocumab significantly reduced low-density lipoprotein cholesterol (LDL-C, or "bad" cholesterol). Alirocumab is an investigational fully human monoclonal antibody targeting the protein PCSK9 (proprotein convertase subtilisin/kexin type 9) that is being evaluated for its ability to lower LDL-C.

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All six trials, ODYSSEY LONG TERM, COMBO I, ALTERNATIVE, OPTIONS I, OPTIONS II, and HIGH FH, met their primary efficacy endpoint of a greater reduction in LDL-C at 24 weeks, versus either active comparator or placebo, which included standard-of-care therapy. Detailed results from these trials were presented as part of a special session on the ODYSSEY program today, and on November 17 during a late-breaker presentation at the American Heart Association (AHA) Scientific Sessions in Chicago, IL. The companies had announced in July that all six studies met their primary efficacy endpoints.

"In these trials patients treated with alirocumab achieved significant and robust LDL-C reductions compared to baseline," said Jennifer Robinson, M.D., M.P.H., Director of the Prevention Intervention Center, Professor, Departments of Epidemiology & Medicine, College of Public Health at the University of Iowa. "New interim results from ODYSSEY LONG TERM provide further support for alirocumab's consistent safety profile, including in more than 500 patients who achieved LDL-C levels lower than 25 mg/dL."

The trials assessed alirocumab in hypercholesterolemic patients who were at high cardiovascular (CV) risk, had an inherited form of high cholesterol known as heterozygous familial hypercholesterolemia (HeFH), and/or a history of intolerance to two or more statins, including one at the lowest dose. All patients received alirocumab in addition to standard-of-care lipid-lowering therapy, with the exception of some patients in ODYSSEY ALTERNATIVE.

Table 1: Summary of Primary Efficacy Endpoint and Most
Common Adverse Events (AEs)

a. Occurred in at least 5 percent of alirocumab-treated patients
b. Previously reported in August 2014
c. P<0.0001
d. 95 percent confidence interval of the LS mean difference vs. placebo: 57.5-69 percent reduction
e. 95 percent confidence interval of the LS mean difference vs. placebo: 59-64 percent reduction
f.  45 patients on atorvastatin 40 mg starting dose switched to rosuvastatin 40 mg
g. For patients on atorvastatin 20 mg starting dose p=0.0004; for patients on atorvastatin 40 mg starting dose p<0.0001
h. For patients on rosuvastatin 10 mg starting dose p<0.0001; patients on rosuvastatin 20 mg starting dose did not reach statistical significance

In a pre-specified interim analysis of the ongoing, 78-week ODYSSEY LONG TERM safety, tolerability and efficacy trial, a generally comparable rate of AEs was observed among the 37 percent (n=562) of alirocumab-treated patients who achieved two consecutive LDL-C values of less than 25 mg/dL, as compared to the overall alirocumab patient population in this trial.

ODYSSEY ALTERNATIVE is the first trial of a PCSK9 inhibitor to reassess statin intolerance, as measured by skeletal muscle AEs, by including a validation arm (atorvastatin 20 mg). In clinical practice, 10 to 25 percent of patients report intolerance to statins, and many have poorly-controlled LDL-C, which puts them at greater risk of CV events.^[1],[2] In this trial, there were fewer skeletal muscle AEs in the alirocumab group compared to patients treated with atorvastatin (32.5 percent versus 46 percent, hazard ratio = 0.61; nominal p value = 0.042), and there was no significant difference when compared to the ezetimibe group (41 percent). In addition, there were numerically fewer discontinuations for skeletal muscle AEs in the alirocumab group, but this did not reach statistical significance (alirocumab 16 percent, ezetimibe 20 percent, atorvastatin 22 percent). In comparison, the overall rate of discontinuations for skeletal muscle AEs across the Phase 2 and 3 alirocumab placebo-controlled studies, where the majority of patients were also on statins, was 0.4 percent for alirocumab (n=2,476) and 0.5 percent for placebo (n=1,276).

Patients in all six randomized, double-blind, Phase 3 ODYSSEY trials received alirocumab via a single, self-administered 1-mililter (mL) subcutaneous injection, every two weeks. Alirocumab-treated patients received the 150 milligram (mg) dose in ODYSSEY LONG TERM and HIGH FH, and the 75 mg dose (increasing to 150 mg if needed to reach pre-specified LDL-C levels) in ODYSSEY ALTERNATIVE, OPTIONS I, OPTIONS II, and COMBO I. In the trials that used an individualized approach with 75 mg and 150 mg doses, the majority of patients reached their LDL-C goal while remaining on the 75 mg dose. Average baseline LDL-C levels in all six trials were between approximately 100-120 mg/dL, with the exception of ODYSSEY ALTERNATIVE and HIGH FH where baseline LDL-C levels were greater than 190 mg/dL.

The six ODYSSEY trials reported at AHA Scientific Sessions 2014, along with results from four other Phase 3 studies, encompass more than 5,000 patients studied in double-blind trials for 24-104 weeks. Regulatory submissions are planned in the U.S. and EU before the end of this year.

The ODYSSEY clinical trial program is ongoing. Click here for more information on alirocumab, LDL-C, and the ODYSSEY studies presented at the AHA Scientific Sessions 2014. Alirocumab is currently under clinical development and its safety and efficacy have not been evaluated by any regulatory authority.

About Sanofi
Sanofi, an integrated global 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).

About Regeneron Pharmaceuticals, Inc.
Regeneron is a leading science-based biopharmaceutical company based in Tarrytown, New York that discovers, invents, develops, manufactures, and commercializes medicines for the treatment of serious medical conditions. Regeneron commercializes medicines for eye diseases, colorectal cancer, and a rare inflammatory condition and has product candidates in development in other areas of high unmet medical need, including hypercholesterolemia, oncology, rheumatoid arthritis, asthma, and atopic dermatitis. Several Regeneron programs are based on human genetics findings. For additional information about the company, please visit www.regeneron.com.

References:
1. Bruckert E, Hayem G, Dejager S, et al. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients — the PRIMO study. Cardiovasc Drugs Ther. 2005;19:403–414.
2. Cohen JD, Brinton EA, Ito MK, Jacobson TA. Understanding statin use in America and gaps in patient education (USAGE): an internet-based survey of 10,138 current and former statin users. J Clin Lipidol. 2012 May-Jun;6(3):208-15.

Sanofi Forward-Looking Statements
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Regeneron Forward-Looking Statements
This news release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. ("Regeneron"), 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. These statements concern, and these risks and uncertainties include, among others, the nature, timing, and possible success and therapeutic applications of Regeneron's products, product candidates, and research and clinical programs now underway or planned, including without limitation alirocumab; unforeseen safety issues resulting from the administration of products and product candidates in patients, including serious complications or side effects in connection with the use of Regeneron's product candidates in clinical trials, such as the ODYSSEY global trial program evaluating alirocumab; the likelihood and timing of possible regulatory approval and commercial launch of Regeneron's late-stage product candidates, including without limitation alirocumab; ongoing regulatory obligations and oversight impacting Regeneron's research and clinical programs and business, including those relating to patient privacy; determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron's ability to continue to develop or commercialize Regeneron's products and product candidates; competing drugs and product candidates that may be superior to Regeneron's products and product candidates; uncertainty of market acceptance and commercial success of Regeneron's products and product candidates; the ability of Regeneron to manufacture and manage supply chains for multiple products and product candidates; coverage and reimbursement determinations by third-party payers, including Medicare and Medicaid; unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its sales or other financial projections or guidance and changes to the assumptions underlying those projections or guidance; the potential for any license or collaboration agreement, including Regeneron's agreements with Sanofi and Bayer HealthCare LLC, to be cancelled or terminated without any further product success; and risks associated with intellectual property of other parties and pending or future litigation relating thereto. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2013 and its Form 10-Q for the quarter ended September 30, 2014. The reader is cautioned not to rely on any forward-looking statements made by Regeneron. Regeneron does not undertake any obligation to update publicly any forward-looking statement, including without limitation any financial projection or guidance, whether as a result of new information, future events, or otherwise.

Contacts Sanofi:

Contacts Regeneron:

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SOURCE Sanofi; Regeneron Pharmaceuticals, Inc.