Sanofi and Regeneron Report Positive Results with Sarilumab in First Phase 3 Rheumatoid Arthritis Registration Trial

PARIS and TARRYTOWN, N.Y., Nov. 22, 2013 /PRNewswire/ -- Sanofi (EURONEXT: SAN andNYSE: SNY) and Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that in the SARIL-RA-MOBILITY Phase 3 clinical trial in adult patients with active rheumatoid arthritis (RA) who were inadequate responders to methotrexate (MTX) therapy, sarilumab (the first fully-human anti-IL-6R monoclonal antibody) treatment in combination with MTX improved disease signs and symptoms as well as physical function, and inhibited progression of joint damage.

"IL-6 blockade is emerging as an important therapeutic approach for rheumatoid arthritis," said Neil Graham, M.B.B.S., M.D., M.P.H., Vice President, Program Direction, Immunology and Inflammation, Regeneron Pharmaceuticals.  "We are encouraged with these Phase 3 results, which demonstrated efficacy at both doses of sarilumab, each administered every other week."

The 52 week SARIL-RA-MOBILITY Phase 3 trial enrolled approximately 1,200 patients with active, moderate-to-severe rheumatoid arthritis, and who were inadequate responders to MTX therapy. Patients were randomized to one of three subcutaneous treatment groups, all in combination with MTX and dosed every other week: sarilumab 200 milligrams (mg), sarilumab 150 mg, or placebo.

Both sarilumab groups showed clinically relevant and statistically significant improvements compared to the placebo group in all three co-primary endpoints (p<0.0001).

(1) Improvement in signs and symptoms of RA at 24 weeks, as measured by the American College of Rheumatology score of 20 percent improvement (ACR20).

• 66 percent, 58 percent, and 33 percent in the sarilumab 200 mg, sarilumab 150 mg, and placebo groups respectively, all in combination with MTX.

(2) Improvement in physical function, as measured by change from baseline in the Health Assessment Question-Disability (HAQ-DI) at week 16. 

(3) Inhibition of progression of structural damage at Week 52, as measured by the change in the modified Van der Heijde total Sharp score (mTSS).

• 0.25, 0.90, and 2.78 in the sarilumab 200 mg, sarilumab 150 mg, and placebo groups respectively, all in combination with MTX.
• The group receiving the 200 mg dose of sarilumab + MTX had a reduction of approximately 90 percent in the radiographic progression assessed by the mTSS compared to the radiographic progression with placebo + MTX at week 52.

ACR Results at week 24

Treatment Group	ACR20^ (%)	ACR50 (%)	ACR70 (%)
200 mg sarilumab + MTX	66*	46*	25*
150 mg sarilumab + MTX	58*	37*	20*
Placebo + MTX	33	17	7

^Primary Endpoint
*p<0.0001 compared to placebo group

In the SARIL-RA-MOBILITY trial, there was a higher incidence of treatment emergent adverse events leading to withdrawal in the sarilumab treatment groups compared to placebo (13.9 percent in 200 mg, 12.5 percent in 150 mg and 4.7 percent in placebo). 

Infections were the most frequently reported adverse events and were reported with a higher incidence in the sarilumab groups compared to placebo, all in combination with MTX (39.6 percent for 200 mg, 40.1 percent for the 150 mg group and 31.1 percent for placebo).  The incidence of serious infections was 4.0 percent in the 200 mg + MTX group, 2.6 percent in the 150 mg + MTX group, and 2.3 percent in the placebo + MTX group.  Among patients treated with sarilumab, a dose dependent decrease in mean neutrophil counts was observed.  Serious infections were not associated with grades 3 and 4 neutropenia in this study.  Increases in mean LDL cholesterol, and transaminases were observed.  These safety findings were consistent with those observed in prior investigational studies with sarilumab.    

"Irreversible joint damage can be a consequence for patients suffering from rheumatoid arthritis, and this is accompanied by reduced physical function in these patients," said Tanya M. Momtahen, M.S., Sarilumab Global Project Head, Sanofi.  "This remains a major concern for rheumatoid arthritis patients.  We are encouraged by these Phase 3 results and the impact sarilumab demonstrated on inhibition of progression of structural damage assessed radiographically in this study."

Additional analyses of efficacy and safety data from the SARIL-RA-MOBILITY study will be presented at a future medical conference.

About Sarilumab
Sarilumab (REGN88/SAR153191) is the first fully-human monoclonal antibody directed against the IL-6 receptor (IL-6R).  Sarilumab is a subcutaneously delivered inhibitor of IL-6 signaling, which binds with high affinity to the IL-6 receptor.  It blocks the binding of IL-6 to its receptor and interrupts the resultant cytokine-mediated inflammatory signaling.  Sarilumab was developed using Regeneron's VelocImmune® antibody technology.

The investigational agent described above is currently under clinical development and its safety and efficacy have not been fully 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
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 markets 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.  For additional information about the company, please visit www.regeneron.com.

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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, 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 sarilumab; 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; the likelihood and timing of possible regulatory approval and commercial launch of Regeneron's late-stage product candidates; ongoing regulatory obligations and oversight impacting Regeneron's research and clinical programs and business; 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, to be cancelled or terminated without any further product success; and risks associated with third party intellectual property 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, 2012 and its Form 10-Q for the quarterly period ended September 30, 2013.  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.

SOURCE Regeneron Pharmaceuticals, Inc.