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COMBINATION THERAPY
KEVZARA combination therapy demonstrated
rapid, sustained, consistent clinical response
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After week 16 in MOBILITY, patients with an inadequate response could have been treated with open-label KEVZARA 200 mg every 2 weeks.1

CO-PRIMARY ENDPOINTS1-3

ACR20 response at week 24: Patients achieved 66%* with KEVZARA 200 mg + MTX compared to 33% with placebo + MTX

ΔHAQ-DI at week 16: -0.58* with KEVZARA 200 mg + MTX compared to -0.30 with placebo + MTX

ΔmTSS from baseline at week 52: 0.25 with KEVZARA 200 mg + MTX vs 2.78 with placebo + MTX*: KEVZARA 200 mg + MTX provided an absolute difference of -2.52 units (CI: -3.38, -1.66) in mean ΔmTSS relative to placebo + MTX

*P<0.0001; P<0.001.

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CO-PRIMARY ENDPOINT DATA (TNF-IR)2-4

ACR20 response at week 24: Patients achieved 61%* with KEVZARA 200 mg + DMARD(s) compared to 34% with placebo + DMARD(s)

ΔHAQ-DI at week 12: 0.49 with KEVZARA 200 mg + DMARD(s) compared to -0.29 with placebo + DMARD(s)

COMBINATION OPEN-LABEL EXTENSION (OLE) STUDY DESIGN

KEVZARA + MTX/DMARD(S) SAFETY AND EFFICACY EVALUATED OVER TIME5

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INCIDENCE OF ADVERSE EVENTS (PRIMARY ENDPOINT)
  • Long-term efficacy was evaluated in adult patients who completed MOBILITY or TARGET and subsequently enrolled in EXTEND OLE5
  • Long-term safety was evaluated in all 2887 adult patients who received ≥1 dose of KEVZARA in combination with DMARD(s)5

*These 2 studies were discontinued due to low enrollment.6,7

Patients participating in the EXTEND OLE trial received KEVZARA 200 mg regardless of prior treatment in the placebo-controlled trials, except for patients who were previously dose-reduced to KEVZARA 150 mg due to safety issues, who continued on KEVZARA 150 mg.5

Patients in the EASY OLE study received KEVZARA 150 mg regardless of their prior treatment.3

STUDY CONTEXT AND LIMITATIONS

OLE STUDY LIMITATIONS AND ADDITIONAL STUDY CONTEXT
  • These data are not included in the KEVZARA US full Prescribing Information
  • Open-label extension studies tend to include patients who respond to treatment and exclude those who discontinue treatment for any reason. As such, evaluating long-term efficacy using continuous variables can be influenced by progressively smaller numbers of patients remaining in the study
  • Data presented are descriptive in nature, and no statistical comparisons are made
  • Clinical data were analyzed based on all available data as observed
LONG-TERM SAFETY ANALYSIS
  • This was a comprehensive safety analysis from pooled studies of patients who received at least 1 dose of sarilumab in combination with DMARD(s)
LONG-TERM EFFICACY ANALYSIS
  • Efficacy assessments in this analysis did not include all of the primary endpoints from the placebo-controlled period of the pivotal trials analyzed
  • For analysis of no radiographic progression, linear extrapolation was used to impute missing data. Patients with missing data after the imputation were considered progressors

DMARDs=disease-modifying antirheumatic drugs.

Given the limitations and context described above, caution should be used in interpreting open-label extension (OLE) data. There are limitations associated with open-label study design, including decreasing sample size and potential continued involvement of responders and attrition of non-responders. Data presented are descriptive in nature and no statistical comparisons are made.

MTX=methotrexate; RA=rheumatoid arthritis; hsCRP=high-sensitivity C-reactive protein; anti-CCP=anti-cyclic citrullinated peptide; RF=rheumatoid factor; SJC=swollen joint count; TJC=tender joint count; q2w=once every 2 weeks; ACR20=American College of Rheumatology 20% improvement criteria; HAQ-DI=Health Assessment Questionnaire-Disability Index; mTSS=modified total Sharp score; TNFi=tumor necrosis factor inhibitor; DMARDs=disease-modifying antirheumatic drugs; TNF-IR=tumor necrosis factor inhibitor inadequate response or intolerant; MTX-IR=methotrexate inadequate response.

References: 1. Genovese MC, Fleischmann R, Kivitz A J, et al. Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: results of a phase III study. Arthritis Rheumatol. 2015;67(6):1424-1437. 2. KEVZARA [prescribing information]. Bridgewater, NJ: Sanofi/Regeneron Pharmaceuticals, Inc. 3. Data on file, Sanofi/Regeneron. Integrated summary. October 25, 2019. 4. Fleischmann R, van Adelsberg J, Lin Y, et al. Sarilumab and nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis and inadequate response or intolerance to tumor necrosis factor inhibitors. Arthritis Rheumatol. 2017;69(2):277-290. 5. Fleischmann R, Genovese M, Lin Y, et al. Long-term safety of sarilumab in rheumatoid arthritis: an integrated analysis with up to 7 years’ follow-up. Rheumatology (Oxford). 2019. doi:10.1093/rheumatology/kez265. [Epub ahead of print]. 6. NIH. Effect of SAR153191 (REGN88) with methotrexate in patients with active rheumatoid arthritis who failed TNF-α blockers. https://clinicaltrials.gov/ct2/show/NCT01217814. Accessed September 3, 2020. 7. National Library of Medicine. An evaluation of sarilumab plus methotrexate compared to etanercept plus methotrexate in RA patients not responding to adalimumab plus methotrexate (RA-COMPARE). https://clinicaltrials.gov/ct2/show/NCT01764997. Accessed September 3, 2020.

QUICK ACR RESPONSE

ACR20 clinical response was observed in MTX-IR and TNF-IR patients as early as 2 weeks in MOBILITY and as quickly as 4 weeks in TARGET, respectively, after the first dose. 1

ACR RESPONSES AT WEEK 242,3

*P<0.0001; P<0.01.

DMARD(s) in TARGET and MOBILITY include MTX, sulfasalazine, leflunomide, and/or hydroxychloroquine.

KEVZARA provided patients with uncontrolled RA
fast, lasting clinical improvement1
ACR20 RESPONSE SUSTAINED THROUGH WEEK 521,2

§P<0.0001, P value is for descriptive purposes only and is not adjusted for multiplicity.

||P<0.0001.

MTX-IR=methotrexate inadequate response; TNF-IR=tumor necrosis factor inhibitor inadequate response or intolerant; ACR20=American College of Rheumatology 20% improvement criteria; MTX=methotrexate; q2w=once every 2 weeks; DMARDs=disease-modifying antirheumatic drugs.

SIGNIFICANT IMPROVEMENTS IN HAQ-DI
∆HAQ-DI: MOBILITY ITT POPULATION1,2

IN MOBILITY, NEARLY

50%

OF MTX-IR PATIENTS MAINTAINED CLINICALLY MEANINGFUL IMPROVEMENT IN PHYSICAL FUNCTION THROUGH WEEK 52 WITH KEVZARA 200 mg + MTX3*
Week 16: KEVZARA 200 mg + MTX: 57% (229/399) vs placebo + MTX: 42% (169/398);
Week 52: KEVZARA 200 mg + MTX: 48% (190/399) vs placebo + MTX: 26% (104/398)

*Minimal clinically important difference. HAQ-DI change from baseline ≥0.3 units.

HAQ-DI=Health Assessment Questionnaire-Disability Index; MTX-IR=methotrexate inadequate response; TNF-IR=tumor necrosis factor inhibitor inadequate response or intolerant; ITT=intent to treat; MTX=methotrexate; q2w=once every 2 weeks; DMARDs=disease-modifying antirheumatic drugs.

INCREASED INHIBITION OF
RADIOGRAPHIC PROGRESSION

56% OF MTX-IR PATIENTS HAD NO RADIOGRAPHIC PROGRESSION WITH KEVZARA
AT 52 WEEKS vs 39% OF PATIENTS TREATED WITH PLACEBO2*

MEAN CHANGE IN mTSS AT WEEK 522,3
91-percent

greater inhibition of joint damage progression
with KEVZARA 200 mg + MTX vs placebo + MTX2

*Defined as mean change from baseline in total Sharp score of ≤0.

Based on post hoc comparisons of mean change in mTSS per treatment group. Week 52 analysis employs linear extrapolation method to impute missing or post rescue data.2

MTX-IR=methotrexate inadequate response; mTSS=modified total Sharp score; MTX=methotrexate.

OPEN-LABEL EXTENSION DATA LIMITATIONS
Given the limitations and context described above, caution should be used in interpreting open-label extension (OLE) data. There are limitations associated with open-label study design, including decreasing sample size and potential continued involvement of responders and attrition of non-responders. Data presented are descriptive in nature and no statistical comparisons are made.
OPEN-LABEL EXTENSION DATA:
INTERPRET WITH CAUTION
CLINICAL RESPONSE OVER 5 YEARS
POOLED ACR20/50/70 RESPONSE OVER TIME1