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HEAD-TO-HEAD MONOTHERAPY
The MONARCH head-to-head superiority
trial measured effect on disease activity,
physical function, and clinical response
with KEVZARA vs adalimumab

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

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)

MONARCH OLE STUDY DESIGN5:
A 24-week, randomized, double-blind, double-dummy, phase 3 superiority study to evaluate the efficacy and safety of KEVZARA 200 mg q2w monotherapy (n=184) vs adalimumab 40 mg q2w monotherapy (n=185) in patients who should not continue treatment with MTX due to intolerance or inadequate response.‡§‖ The primary endpoint was ΔDAS28-ESR; secondary endpoints included ΔDAS28-ESR <2.6, ACR20/50/70, ΔDAS28-CRP, ΔHAQ-DI.5

PRIMARY ENDPOINT DATA5

  • Change from baseline DAS28-ESR at 24 weeks: -3.28# with KEVZARA 200 mg q2w monotherapy compared to -2.20 with adalimumab 40 mg q2w monotherapy
  • The safety profiles of KEVZARA and adalimumab were generally comparable except for neutropenia and injection site erythema for KEVZARA and headache and RA for adalimumab

*P<0.0001; P<0.001; Efficacy analyses were conducted in the ITT population, which included all randomized patients, including those who increased the dose frequency of adalimumab or matching placebo. Data collected after permanent treatment discontinuation period were excluded; §After week 16, dose escalation to adalimumab qw was permitted for patients who did not achieve ≥20% improvement in TJC and SJC;The recommended dose of adalimumab SC is 40 mg q2w. Some patients not taking concomitant MTX may derive additional benefit from increasing the SC dosing frequency to 40 mg qw; see adalimumab full Prescribing Information.5,6; #P<0.0001; difference: -1.08 (95% CI: -1.36 to -0.79).5

MONARCH STUDY CONTEXT AND LIMITATIONS

ADDITIONAL STUDY CONTEXT

  • MONARCH data are not included in the KEVZARA US full Prescribing Information
  • DAS28-ESR and FACIT-Fatigue were endpoints in MONARCH; however, there are no DAS28-ESR or FACIT-Fatigue data in the KEVZARA US full Prescribing Information

USE OF ADALIMUMAB

  • Adalimumab and KEVZARA have different indications and can be used differently in clinical practice
  • Dose escalation from adalimumab 40 mg q2w to 40 mg qw was permitted after week 16 in patients who had not achieved at least 20% improvement in TJC and SJC. By week 24, dosing for 8.6% of patients on adalimumab was adjusted

STUDY LIMITATIONS (MONARCH)

  • KEVZARA and adalimumab can be used as monotherapy or in combination with nonbiologic DMARDs. In MONARCH, both agents were only used as monotherapy
  • The efficacy of KEVZARA monotherapy has not been compared to that of KEVZARA + MTX or adalimumab + MTX
  • MONARCH did not evaluate radiographic outcomes in either treatment group

Given the limitations and context described above, caution should be used in interpreting monotherapy data.

MONARCH LONG-TERM STUDY DESIGN

OPEN-LABEL EXTENSION (OLE) STUDY DESIGN: A 276-week (ongoing) randomized, double-blind, double-dummy phase 3 superiority study extension designed to assess the safety and efficacy of long-term continuous KEVZARA monotherapy and switching from adalimumab monotherapy to KEVZARA monotherapy in 320 adult patients who completed the MONARCH study. Primary endpoint was safety. Secondary endpoints included DAS28-ESR, DAS28-CRP, HAQ-DI, CDAI, SDAI, and ACR20/50/70.7

PRIMARY ENDPOINT DATA7

  • Overall, safety observations in the OLE population were consistent with those in the MONARCH study and previous studies of KEVZARA, with no unexpected safety signals
  • Long-term safety and efficacy of KEVZARA were demonstrated in patients who continued treatment with KEVZARA from MONARCH through OLE ≥72 weeks

MONARCH LONG-TERM STUDY CONTEXT AND LIMITATIONS

OLE AND ADDITIONAL STUDY CONTEXT

  • These data are not included in the KEVZARA US full Prescribing Information
  • Long-term safety analysis included all patients who received at least 1 dose of KEVZARA monotherapy
  • Analysis of clinical data was based on all available data as observed
  • Data presented are descriptive in nature and no statistical comparisons are made
  • OLE 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

Given the limitations and context described above, caution should be used in interpreting 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.

Please see Study Context and Limitations above for more information.

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; DMARDs=disease-modifying antirheumatic drugs; TNF-IR=tumor necrosis factor inhibitor inadequate response or intolerant; MTX-IR=methotrexate inadequate response; DAS28-ESR=Disease Activity Score-28 Erythrocyte Sedimentation Rate; DAS28-CRP=disease activity score 28-C-reactive protein; ITT=intent to treat; qw=once daily; SC=subcutaneous; CDAI=Clinical Disease Activity Index; SDAI=Simple Disease Activity Index.

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. Burmester GR, Lin Y, Patel R, et al. Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial. Ann Rheum Dis. 2017;76(5):840-847. 6. Humira [package insert]. North Chicago, IL: AbbVie Inc; 2019. 7. Burmester GR, Strand V, Rubbert-Roth A, et al. Safety and efficacy of switching from adalimumab to sarilumab in patients with rheumatoid arthritis in the ongoing MONARCH open-label extension. RMD Open. 2019;5(2):e001017. doi:10.1136/rmdopen-2019-001017.

GREATER IMPROVEMENT IN DISEASE
ACTIVITY vs ADALIMUMAB

KEVZARA monotherapy was superior to adalimumab monotherapy in meeting primary endpoint of mean change from baseline to week 24 in DAS28-ESR.1

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greater improvement in DAS28-ESR than adalimumab at week 241

MONARCH (MTX-IR) CHANGE IN DAS28-ESR AT WEEK 241

*Difference: -1.08 (95% CI: -1.36 to -0.79).

DAS28-ESR=Disease Activity Score-28 Erythrocyte Sedimentation Rate; MTX-IR=methotrexate inadequate response; LS=least squares; SE=standard error; q2w=once every 2 weeks.


AT WEEK 24
More than 3x as many
KEVZARA patients achieved low disease activity
(DAS28-ESR <2.6) vs adalimumab monotherapy
(26.6% vs 7.0%; P<0.0001)1

IMPROVED PHYSICAL FUNCTION vs ADALIMUMAB

Significantly greater improvements in HAQ-DI were achieved with KEVZARA monotherapy vs adalimumab monotherapy through week 24.1

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greater improvement in HAQ-DI vs adalimumab at
week 241

MONARCH (MTX-IR)
CHANGE FROM BASELINE IN HAQ-DI AT WEEK 241

HAQ-DI=Health Assessment Questionnaire-Disability Index; MTX-IR=methotrexate inadequate response; LS=least squares; q2w=once every 2 weeks.

GREATER CLINICAL RESPONSE vs ADALIMUMAB

Significantly more patients achieved ACR responses with KEVZARA monotherapy vs adalimumab monotherapy through week 24.1

MONARCH: (MTX-IR)
ACR RESPONSE AT WEEK 241

*P<0.01.
ACR20=American College of Rheumatology 20% improvement criteria; MTX-IR=methotrexate inadequate response; q2w=once every 2 weeks.

More patients achieved greater control of disease activity
with KEVZARA vs adalimumab1
MONARCH OPEN-LABEL EXTENSION
DATA LIMITATIONS
Given the limitations and context described above, caution should be used in interpreting 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.
MONARCH OPEN-LABEL EXTENSION DATA: INTERPRET WITH CAUTION
CHANGE IN DISEASE ACTIVITY
MEAN CHANGE FROM BASELINE IN DAS28-ESR1-3

DAS28-ESR=Disease Activity Score-28 Erythrocyte Sedimentation Rate; SE=standard error; q2w=once every 2 weeks.

Changes in disease activity were measured both in patients who
continued treatment with KEVZARA monotherapy and in those who
switched treatment from adalimumab to KEVZARA

MONARCH OPEN-LABEL EXTENSION DATA: INTERPRET WITH CAUTION
IMPROVEMENT IN PHYSICAL FUNCTION
MEAN HAQ-DI OVER TIME2,3

HAQ-DI=Health Assessment Questionnaire-Disability Index; SE=standard error; q2w=once every 2 weeks.

MONARCH OPEN-LABEL EXTENSION DATA: INTERPRET WITH CAUTION
OBSERVED ACR CLINICAL RESPONSE
ACR20/50/70 AT WEEKS 0 AND 48 IN OPEN-LABEL EXTENSION (OLE)2