Clinical Trials

Date: 2016-11-16

Type of information: Results

phase: 3

Announcement: presentation of results at the American College of Rheumatology (ACR) Annual Meeting

Company: Sanofi (France) Regeneron Pharmaceuticals (USA - NY)

Product: sarilumab (REGN88/SAR153191)

Action mechanism: monoclonal antibody. Sarilumab (REGN88/SAR153191) is a fully human monoclonal antibody directed against the alpha subunit of the IL-6 receptor complex (IL-6R Alpha).  Sarilumab is a high-affinity, subcutaneously delivered inhibitor of IL-6 signaling.  It blocks the binding of IL-6 to its receptor and interrupts the resultant cytokine-mediated inflammatory signaling cascade.  Sarilumab was developed using Regeneron's VelocImmune® antibody technology.

Disease: rheumatoid arthritis

Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases

Country: Chile, Czech Republic, Germany, Hungary, Israel, Republic of Korea, Peru, Poland, Romania, Russian Federation, South Africa, Spain, Ukraine, UK, USA

Trial details:

• The SARIL-RA-MONARCH study has been designed to demonstrate that sarilumab monotherapy is superior to adalimumab monotherapy with respect to signs and symptoms as assessed by disease activity score 28 (DAS28)-erythrocyte sedimentation rate (ESR) in patients with active rheumatoid arthritis (RA) who are either intolerant of, or considered inappropriate candidates for continued treatment with methotrexate (MTX), or after at least 12 weeks of continuous treatment with MTX, are determined to be inadequate responders.
• The study enrolled 369 adults that 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. (NCT02332590)

Latest news:

• • On November 16, 2016, Sanofi and Regeneron Pharmaceuticals have presented results of SARIL-RA-MONARCH, a Phase 3 study, which demonstrated the superiority of investigational sarilumab monotherapy versus adalimumab monotherapy in improving the clinical signs and symptoms in adults with active rheumatoid arthritis. The results are being presented  at an oral session during the American College of Rheumatology (ACR) Annual Meeting in Washington, DC. Top-line results were previously announced in March 2016 (see below).
• 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).  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).
• 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).
• - 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).
• - 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).
• 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). 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. • On March 11, 2016, Regeneron Pharmaceuticals and Sanofi announced that a Phase 3 monotherapy study met its primary endpoint demonstrating that sarilumab was superior to adalimumab (marketed by AbbVie as HUMIRA®) in improving signs and symptoms in patients with active rheumatoid arthritis (RA) at Week 24.
• The primary endpoint was change from baseline in DAS28-ESR at 24 weeks, which demonstrated a statistically significant difference in favor of sarilumab (-3.25 for sarilumab compared to -2.22 for adalimumab, p less than 0.0001). The study also met clinically important secondary endpoints including improvements in signs and symptoms of RA as measured by patients achieving a 20 percent improvement in the American College of Rheumatology (ACR) criteria (72 percent for sarilumab vs. 58 percent for adalimumab, p less than 0.01). Additional positive secondary endpoints included ACR50 and ACR70 response, and improvement in physical function, as measured by the Health Assessment Questionnaire - Disability Index (HAQ-DI) as compared to adalimumab (p less than 0.01 for all of these measures). 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, and ESR, a laboratory measure for inflammation.
• 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.

Is general: Yes