Paris, France and Tarrytown, N.Y. – November 16, 2016 – Sanofi and Regeneron Pharmaceuticals, Inc. today will present results of SARIL-RA-MONARCH, a Phase 3 study, which demonstrated the superiority of investigational sarilumab monotherapy versus adalimumab (marketed by AbbVie as HUMIRA®) monotherapy in improving the clinical signs and symptoms in adults with active rheumatoid arthritis (RA). The results are being presented today at an oral session during the American College of Rheumatology (ACR) Annual Meeting in Washington, DC.
“Approximately 30 percent of people with RA are being treated with biologic monotherapy largely due to intolerance to methotrexate,” said Dr. Gerd Burmester, Charité – University Medicine, Berlin, Germany and lead study author. “In the MONARCH monotherapy study, sarilumab was more effective than adalimumab, which is one of the most commonly used biologics today.”
The SARIL-RA-MONARCH study enrolled 369 adults with active RA who were inadequate responders to, intolerant of, or inappropriate candidates for methotrexate (MTX). Patients were randomized to receive either subcutaneous sarilumab monotherapy (200 mg every 2 weeks) or adalimumab monotherapy (40 mg every 2 weeks); patients who did not respond adequately to adalimumab could increase to weekly dosing. Top-line results were previously announced in March 2016.[i]
The primary endpoint was change from baseline in DAS28-ESR at 24 weeks, which demonstrated a statistically significant difference in favor of sarilumab (-3.28 for sarilumab compared to -2.20 for adalimumab, p less than 0.0001).1 DAS28-ESR is a measure of disease activity in RA, which includes the evaluation of 28 joints in the body for tenderness and swelling, a general health assessment by the patient, and ESR, a laboratory measure for inflammation.[ii]
The study also met other important endpoints including improvement in American College of Rheumatology (ACR) criteria and the Health Assessment Questionnaire – Disability Index (HAQ-DI).1 Results included:
- A greater improvement in signs and symptoms of RA with sarilumab as measured by the proportion of patients achieving a 20 percent improvement in the ACR criteria (72 percent for sarilumab vs. 58 percent for adalimumab, p less than 0.01). The proportion of patients achieving ACR50 was also higher with sarilumab (45 percent for sarilumab vs. 29 percent for adalimumab, p=0.0017) as well as for ACR70 (23 percent for sarilumab vs. 11 percent for adalimumab, p=0.0036).1
- Rates of DAS28-ESR remission (score<2.6) were higher for sarilumab vs. adalimumab (26 percent for sarilumab vs. 7 percent for adalimumab, p less than 0.0001).1
- Improvements in HAQ-DI were observed with sarilumab vs adalimumab. The change in baseline to week 24 in HAQ-DI for sarilumab was -0.61 vs. -0.43 for adalimumab (p=0.0037).1
The study also observed greater numerical response in Clinical Disease Activity Index (CDAI). The change in baseline to week 24 was -28.9 for sarilumab vs. -25.2 for adalimumab. Higher rates of CDAI remission were also observed for sarilumab (7 percent) vs. adalimumab (2 percent).1 Adults treated with sarilumab also experienced greater improvement in functional disability, pain and fatigue over adults treated with adalimumab. These improvements included patient-reported outcomes, which were measured by Medical Outcomes Short Form 36 Health Survey; physician component summary score (PCS) and mental component summary score (MCS); and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F).
The incidence of adverse events (64 percent for both groups), serious adverse events (5 percent for sarilumab vs. 7 percent for adalimumab), infections (29 percent for sarilumab vs. 28 percent for adalimumab), and serious infections (1 percent for both groups) were generally similar between groups. Neutropenia, which was not associated with infections, was more common with sarilumab (14 percent for sarilumab vs. 1 percent for adalimumab), as has been seen in previous studies with IL-6 inhibitors. Injection site erythema (8 percent sarilumab vs. 3 percent adalimumab) was also more common with sarilumab.1
The safety and efficacy of sarilumab have not been fully evaluated by any regulatory authority. If approved, sarilumab will be marketed by Regeneron and Sanofi Genzyme, the specialty care global business unit of Sanofi.
[i] Burmester G. et al.#3321 Efficacy and Safety of Sarilumab Versus Adalimumab in a Phase 3, Randomized, Double-blind, Monotherapy Study in Patients With Active Rheumatoid Arthritis With Intolerance or Inadequate Response to Methotrexate. Arthritis Rheumatol. 2016; 68 (suppl 10).
[ii] Arthritis Foundation. “Measuring Disease Activity in Rheumatoid Arthritis.” http://www.arthritis.org/living-with-arthritis/life-stages/remission/measuring-disease-activity.php. Last accessed October 2016.