Read Important Safety Information,
including Boxed WARNING
CONTACT A REPREQUEST SAMPLESLink to the KEVZARA Experience Voucher ProgramVOUCHER PROGRAM

FDA APPROVED

To treat adult patients with polymyalgia rheumatica (PMR) who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper.

APPROVAL PRESS RELEASE 

clinical-remission-data-img
CLINICAL REMISSION DATA
KEVZARA has clinical remission data and
open-label extension data over 4 years
chart-1
chart-1

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.

chart-1
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
chart-1
chart-1
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.

CLINICAL REMISSION DATA (DAS28-CRP <2.6)
WITH KEVZARA
REMISSION DATA (DAS28-CRP <2.6) AT WEEK 24: MOBILITY1,2

Measures of remission do not imply drug-free remission or complete absence of disease.

DAS28-CRP=disease activity score 28-C-reactive protein; MTX=methotrexate; MTX-IR=methotrexate inadequate response; TNF-IR=tumor necrosis factor inhibitor inadequate response or intolerant; q2w=once every 2 weeks; DMARDs=disease-modifying antirheumatic drugs.

CLINICAL REMISSION DATA (SDAI ≤3.3/CDAI ≤2.8)
WITH KEVZARA

KEVZARA 200 mg + MTX SHOWED IMPROVEMENT IN CDAI REMISSION COMPARED TO PLACEBO + MTX IN MOBILITY (MTX-IR)

REMISSION DATA AT WEEK 24: MOBILITY1,4

Measures of remission do not imply drug-free remission or complete absence of disease.

SDAI=Simple Disease Activity Index; CDAI=Clinical Disease Activity Index; MTX=methotrexate; MTX-IR=methotrexate inadequate response; TNF-IR=tumor necrosis factor inhibitor inadequate response or intolerant; q2w=once every 2 weeks; DMARDs=disease-modifying antirheumatic drugs.

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 REMISSION DATA (SDAI ≤3.3/CDAI ≤2.8)
OVER 4 YEARS
REMISSION DATA: SDAI ≤3.3/CDAI ≤2.84,6

Measures of remission do not imply drug-free remission or complete absence of disease.

SDAI=Simple Disease Activity Index; CDAI=Clinical Disease Activity Index; MTX-IR=methotrexate inadequate response; TNF-IR=tumor necrosis factor inhibitor inadequate response or intolerant; MTX=methotrexate; q2w=once every 2 weeks; DMARDs=disease-modifying antirheumatic drugs.

OPEN-LABEL EXTENSION DATA:
INTERPRET WITH CAUTION
CLINICAL REMISSION DATA (DAS28-CRP <2.6)
OVER 4 YEARS
REMISSION DATA: DAS28-CRP<2.67

Measures of remission do not imply drug-free remission or complete absence of disease.

DAS28-CRP=disease activity score 28-C-reactive protein; MTX-IR=methotrexate inadequate response; TNF-IR=tumor necrosis factor inhibitor inadequate response or intolerant; MTX=methotrexate; q2w=once every 2 weeks; DMARDs=disease-modifying antirheumatic drugs.

INDICATIONS

KEVZARA is indicated for treatment of adult patients with:

  • moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).
  • polymyalgia rheumatica (PMR) who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper.

IMPORTANT SAFETY INFORMATION

WARNING: RISK OF SERIOUS INFECTIONS
Patients treated with KEVZARA are at increased risk for developing serious infections that may lead to hospitalization or death. Opportunistic infections have also been reported in patients receiving KEVZARA. Most patients who developed infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.
Avoid use of KEVZARA in patients with an active infection.
Reported infections include:
  • Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients should be tested for latent tuberculosis before KEVZARA use and during therapy. Treatment for latent infection should be initiated prior to KEVZARA use.
  • Invasive fungal infections, such as candidiasis, and pneumocystis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
  • Bacterial, viral and other infections due to opportunistic pathogens.
Closely monitor patients for signs and symptoms of infection during treatment with KEVZARA. If a serious infection develops, interrupt KEVZARA until the infection is controlled.
Consider the risks and benefits of treatment with KEVZARA prior to initiating therapy in patients with chronic or recurrent infection.

CONTRAINDICATION

Do not use KEVZARA in patients with known hypersensitivity to sarilumab or any of the inactive ingredients.

WARNINGS AND PRECAUTIONS

  • Infections. Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving immunosuppressive agents including KEVZARA. The most frequently observed serious infections with KEVZARA included pneumonia and cellulitis. Among opportunistic infections, TB, candidiasis, and pneumocystis were reported with KEVZARA.
    • Hold treatment with KEVZARA if a patient develops a serious infection or an opportunistic infection.
    • Patients with latent TB should be treated with standard antimycobacterial therapy before initiating KEVZARA. Consider anti-TB therapy prior to initiation of KEVZARA in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but having risk factors for TB infection.
    • Consider the risks and benefits of treatment prior to initiating KEVZARA in patients who have: chronic or recurrent infection, a history of serious or opportunistic infections, underlying conditions that may predispose them to infection, been exposed to TB, or lived in or traveled to areas of endemic TB or endemic mycoses.
    • Viral reactivation has been reported with immunosuppressive biologic therapies. Cases of herpes zoster were observed in clinical studies with KEVZARA.
  • Laboratory Abnormalities. Treatment with KEVZARA was associated with decreases in absolute neutrophil counts (including neutropenia), and platelet counts; and increases in transaminase levels and lipid parameters (LDL, HDL cholesterol, and/or triglycerides). Increased frequency and magnitude of these elevations were observed when potentially hepatotoxic drugs (e.g., MTX) were used in combination with KEVZARA. Assess neutrophil count, platelet count, and ALT/AST levels prior to initiation with KEVZARA. Monitor these parameters 4 to 8 weeks after start of therapy and every 3 months thereafter. Assess lipid parameters 4 to 8 weeks after start of therapy, then at 6 month intervals.
  • Gastrointestinal Perforation. GI perforation risk may be increased with concurrent diverticulitis or concomitant use of NSAIDs or corticosteroids. Gastrointestinal perforations have been reported in clinical studies, primarily as complications of diverticulitis. Promptly evaluate patients presenting with new onset abdominal symptoms.
  • Immunosuppression. Treatment with immunosuppressants may result in an increased risk of malignancies. The impact of treatment with KEVZARA on the development of malignancies is not known but malignancies have been reported in clinical studies.
  • Hypersensitivity Reactions. Hypersensitivity reactions have been reported in association with KEVZARA. Hypersensitivity reactions that required treatment discontinuation were reported in 0.3% of patients in controlled RA trials. Injection site rash, rash, and urticaria were the most frequent hypersensitivity reactions. Advise patients to seek immediate medical attention if they experience any symptoms of a hypersensitivity reaction. If anaphylaxis or other hypersensitivity reaction occurs, stop administration of KEVZARA immediately. Do not administer KEVZARA to patients with known hypersensitivity to sarilumab.
  • Active Hepatic Disease and Hepatic Impairment. Treatment with KEVZARA is not recommended in patients with active hepatic disease or hepatic impairment, as treatment with KEVZARA was associated with transaminase elevations.
  • Live Vaccines. Avoid concurrent use of live vaccines during treatment with KEVZARA due to potentially increased risk of infections. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving KEVZARA.

ADVERSE REACTIONS

  • For Rheumatoid Arthritis: The most common serious adverse reactions were infections. The most frequently observed serious infections included pneumonia and cellulitis. The most common adverse reactions (occurred in at least 3% of patients treated with KEVZARA + DMARDs) are neutropenia, increased ALT, injection site erythema, upper respiratory infections, and urinary tract infections.
  • For Polymyalgia Rheumatica: Serious adverse reactions of neutropenia occurred in 2 patients (3.4%) in the KEVZARA group compared to none in the placebo group. The proportion of patients with serious infections was similar in the KEVZARA group (5.1%) compared to the placebo group (5.2%). The common adverse reactions occurring in ≥5% of patients treated with KEVZARA were neutropenia, leukopenia, constipation, rash pruritic, myalgia, fatigue, and injection site pruritus.

DRUG INTERACTIONS

  • Exercise caution when KEVZARA is co-administered with CYP substrates with a narrow therapeutic index (e.g. warfarin or theophylline), or with CYP3A4 substrates (e.g. oral contraceptives or statins) as there may be a reduction in exposure which may reduce the activity of the CYP3A4 substrate.
  • Elevated interleukin-6 (IL-6) concentration may down-regulate CYP activity such as in patients with RA and hence increase drug levels compared to subjects without RA. Blockade of IL-6 signaling by IL-6Rα antagonists such as KEVZARA might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to altered drug concentrations.

USE IN SPECIFIC POPULATIONS

  • KEVZARA should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Because monoclonal antibodies could be excreted in small amounts in human milk, the benefits of breastfeeding and the potential adverse effects on the breastfed child should be considered along with the mother’s clinical need for KEVZARA.
  • Use caution when treating the elderly.

Advise patients to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

Please click here to see full Prescribing Information, including Boxed WARNING.

INDICATIONS

KEVZARA is indicated for treatment of adult patients with:

  • moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).
  • polymyalgia rheumatica (PMR) who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper.

IMPORTANT SAFETY INFORMATION

WARNING: RISK OF SERIOUS INFECTIONS
Patients treated with KEVZARA are at increased risk for developing serious infections that may lead to hospitalization or death. Opportunistic infections have also been reported in patients receiving KEVZARA. Most patients who developed infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.
Avoid use of KEVZARA in patients with an active infection.
Reported infections include:
  • Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients should be tested for latent tuberculosis before KEVZARA use and during therapy. Treatment for latent infection should be initiated prior to KEVZARA use.
  • Invasive fungal infections, such as candidiasis, and pneumocystis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
  • Bacterial, viral and other infections due to opportunistic pathogens.
Closely monitor patients for signs and symptoms of infection during treatment with KEVZARA. If a serious infection develops, interrupt KEVZARA until the infection is controlled.
Consider the risks and benefits of treatment with KEVZARA prior to initiating therapy in patients with chronic or recurrent infection.

CONTRAINDICATION

Do not use KEVZARA in patients with known hypersensitivity to sarilumab or any of the inactive ingredients.

WARNINGS AND PRECAUTIONS

  • Infections. Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving immunosuppressive agents including KEVZARA. The most frequently observed serious infections with KEVZARA included pneumonia and cellulitis. Among opportunistic infections, TB, candidiasis, and pneumocystis were reported with KEVZARA.
    • Hold treatment with KEVZARA if a patient develops a serious infection or an opportunistic infection.
    • Patients with latent TB should be treated with standard antimycobacterial therapy before initiating KEVZARA. Consider anti-TB therapy prior to initiation of KEVZARA in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but having risk factors for TB infection.
    • Consider the risks and benefits of treatment prior to initiating KEVZARA in patients who have: chronic or recurrent infection, a history of serious or opportunistic infections, underlying conditions that may predispose them to infection, been exposed to TB, or lived in or traveled to areas of endemic TB or endemic mycoses.
    • Viral reactivation has been reported with immunosuppressive biologic therapies. Cases of herpes zoster were observed in clinical studies with KEVZARA.
  • Laboratory Abnormalities. Treatment with KEVZARA was associated with decreases in absolute neutrophil counts (including neutropenia), and platelet counts; and increases in transaminase levels and lipid parameters (LDL, HDL cholesterol, and/or triglycerides). Increased frequency and magnitude of these elevations were observed when potentially hepatotoxic drugs (e.g., MTX) were used in combination with KEVZARA. Assess neutrophil count, platelet count, and ALT/AST levels prior to initiation with KEVZARA. Monitor these parameters 4 to 8 weeks after start of therapy and every 3 months thereafter. Assess lipid parameters 4 to 8 weeks after start of therapy, then at 6 month intervals.
  • Gastrointestinal Perforation. GI perforation risk may be increased with concurrent diverticulitis or concomitant use of NSAIDs or corticosteroids. Gastrointestinal perforations have been reported in clinical studies, primarily as complications of diverticulitis. Promptly evaluate patients presenting with new onset abdominal symptoms.
  • Immunosuppression. Treatment with immunosuppressants may result in an increased risk of malignancies. The impact of treatment with KEVZARA on the development of malignancies is not known but malignancies have been reported in clinical studies.
  • Hypersensitivity Reactions. Hypersensitivity reactions have been reported in association with KEVZARA. Hypersensitivity reactions that required treatment discontinuation were reported in 0.3% of patients in controlled RA trials. Injection site rash, rash, and urticaria were the most frequent hypersensitivity reactions. Advise patients to seek immediate medical attention if they experience any symptoms of a hypersensitivity reaction. If anaphylaxis or other hypersensitivity reaction occurs, stop administration of KEVZARA immediately. Do not administer KEVZARA to patients with known hypersensitivity to sarilumab.
  • Active Hepatic Disease and Hepatic Impairment. Treatment with KEVZARA is not recommended in patients with active hepatic disease or hepatic impairment, as treatment with KEVZARA was associated with transaminase elevations.
  • Live Vaccines. Avoid concurrent use of live vaccines during treatment with KEVZARA due to potentially increased risk of infections. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving KEVZARA.

ADVERSE REACTIONS

  • For Rheumatoid Arthritis: The most common serious adverse reactions were infections. The most frequently observed serious infections included pneumonia and cellulitis. The most common adverse reactions (occurred in at least 3% of patients treated with KEVZARA + DMARDs) are neutropenia, increased ALT, injection site erythema, upper respiratory infections, and urinary tract infections.
  • For Polymyalgia Rheumatica: Serious adverse reactions of neutropenia occurred in 2 patients (3.4%) in the KEVZARA group compared to none in the placebo group. The proportion of patients with serious infections was similar in the KEVZARA group (5.1%) compared to the placebo group (5.2%). The common adverse reactions occurring in ≥5% of patients treated with KEVZARA were neutropenia, leukopenia, constipation, rash pruritic, myalgia, fatigue, and injection site pruritus.

DRUG INTERACTIONS

  • Exercise caution when KEVZARA is co-administered with CYP substrates with a narrow therapeutic index (e.g. warfarin or theophylline), or with CYP3A4 substrates (e.g. oral contraceptives or statins) as there may be a reduction in exposure which may reduce the activity of the CYP3A4 substrate.
  • Elevated interleukin-6 (IL-6) concentration may down-regulate CYP activity such as in patients with RA and hence increase drug levels compared to subjects without RA. Blockade of IL-6 signaling by IL-6Rα antagonists such as KEVZARA might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to altered drug concentrations.

USE IN SPECIFIC POPULATIONS

  • KEVZARA should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Because monoclonal antibodies could be excreted in small amounts in human milk, the benefits of breastfeeding and the potential adverse effects on the breastfed child should be considered along with the mother’s clinical need for KEVZARA.
  • Use caution when treating the elderly.

Advise patients to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

Please click here to see full Prescribing Information, including Boxed WARNING.