Dupixent is indicated for the treatment of moderatetosevere atopic d - PDF document

1 Dupixent is indicated for the treatment
Dupixent is indicated for the treatment of moderate-to-severe atopic dermatitis in adult patients who are candidates for systemic therapy.Data Issued in February 2018For further information please review the Israeli PI approved by MoH First targeted biologic for adults with moderate-to-severe atopic dermatitisRapid and sustained improvement in: Lesion extent and severity Quality-of-life measuresDiscontinuation rates due to adverse events were lower than with placebo at 52 weeksPsrk1xivq xspivefmpmxy tvs�piReferences: 1. Simpson EL et al. J Am Acad Dermatol. 2016;74(3):491-498. Leung DYM et al. J Clin Invest. 2004;113(1):611-617. Suárez-Fariñas M et al. J Allergy Clin Immunol. 2011;127(4):914-964. Gittler JK et al. J Allergy Clin Immunol. 2012;130(6):1344-1314.   Dupixent Israeli SPC 02.18 6. Simpson EL et al. N Engl J Med. 2016. doi: 10.1016/NEJMoa16100020 Data on file (SOLO Continue enrollment) Clinical Trials.gov. n open-label trial of dupilumab (REGN668.S R231893) in patients with atopic dermatitis. Blauvelt et al. Lancet. 2017;389(10086):2287-2303. doi: 10.1016/S0140-6736(17)31191-1 10. Data on file (C FÉ and pooled SOLO data). 11. Simpson EL. Dermatol Ther (Heidelb). 2017;7(2):243-248. 12. Hongbo Y et al. J Invest Dermatol. 2001;121(4):619-664. . Data on file (12-week DLQI Kaplan-Meier curve). 14. Data on file (C FÉ pruritus and DLQI scores).Most common adverse reactions were injection site reactions, conjunctivitis, blepharitis, and oral herpes. Wejixy tvs�pi iwxefpmwlih yt xs 96 wiiow Pooled data from placebo-controlled monotherapy clinical studies and placebo-controlled concomitant therapy with TCS study; patients exposed to DUPIXENT 300 mg QW or 300 mg Q2W.The safety and efficacy of DUPIXENT have not been established in the treatment of asthma. Discontinuation rate (%) DUPIXENT Q2W + TCS (n=110)Placebo + TCS (n=315) 012345678 1

2 .8%7.6% System organ classAdverse reacti
.8%7.6% System organ classAdverse reactionInfections and infestationsCommon(≥1% to <10%)Conjunctivitis,oral herpesBlood and lymphatic system disordersCommon(≥1% to <10%)EosinophiliaImmune system disordersVery rare(0 to ≤1%)Serum sickness/serum sickness-like reactionsNervous system disorder frequencyCommon(≥1% to <10%)HeadacheEye disordersCommon(≥1% to <10%)Conjunctivitis allergic, eye pruritus, blepharitisGeneral disorders and administration site conditionsVery common (≥10%)Injection site reactions Adverse reactions for DUPIXENT in clinical studies,a Adverse reactions for DUPIXENT in clinical studies5,9,a CHRONOS: Discontinuations due toadverse events at weeks Discontinuation rates due to adverse events were lower than placebo at 52 weeks Psrk1xivq wejixy erh xspivefmpmxy tvs�pi mr efszi 64If a systemic hypersensitivity reaction (immediate or delayed) occurs, DUPIXENT should be discontinued immediately and appropriate therapy initiatedPatients who develop conjunctivitis that does not resolve following standard treatment should undergo ophthalmological examinationPatients with comorbid asthma should not adjust or stop their asthma treatments without consulting their physicians. Monitor patients with comorbid asthma carefully following discontinuation of DUPIXENT 5,b 11 2 weeks300 mg every 2 weeksmoving forward2 subcutaneousinjections subcutaneousinjection subcutaneousinjectionLoading dose 300 mg 300 mg300 mg No weight-based dose adjustments neededSelf-administered, subcutaneous, biweekly dosing in adultsDUPIXENT should be stored in a refrigerator, but not frozen (2°C to 8°C)May be kept at room temperature, under 21°C, for up to 14 days NRS, numerical rating scale.De�ned as a ≥4-point improvement in pruritus NRS on a 0- to 10-point scale.Emollient background regimen/therapy was required.Defined as a ≥4-point improvement in DLQI on a 0

3 - to 30-point scale.Last observation car
- to 30-point scale.Last observation carried forward.Rapid and sustained improvement Retmh erh wywxemrih firi�xw Dermatology Life Quality Index (DLQI) The measurement for significance at 2 weeks was a post-hoc analysis.CHRONOS trial design: A randomized, double-blind, placebo-controlled trial of adults with moderate-to-severe atopic dermatitis (N=740), randomized to DUPIXENT 300 mg Q2W plus topical corticosteroids or placebo plus topical corticosteroids for 52 weeks. The coprimary endpoints were at least 75% improvement on the Eczema rea and Severity Index (E SI-71), and an Investigator's Global ssessment (IG ) score of 0 or 1 with a reduction from baseline of ≥2 points at 16 weeks. 106 patients were randomized to DUPIXENT 300 mg Q2W plus topical corticosteroids and 311 patients were randomized to placebo plus topical corticosteroids for 52 weeks.Data derived as a result of post-hoc analysis. CHRONOS: Patients achieving clinically meaningful improvement in pruritus NRS CHRONOS: Patients achieving clinically meaningful improvement in DLQI 0 4 8 12 16 20 24 28 32 36 40 44 48 52 50 40 30 20 Percent with 4-point improvement in pruritus NRS 13Weeks Placebo + TCS (n=249) DUPIXENT 300 mg Q2W + TCS (n=86) Weeks 70 80 90 60 50 40 30 20 100 Percent with4-point improvement in DLQI 0 4 8 12 16 20 24 28 32 36 40 44 48 52 30548085 ~2.5xPP Placebo + TCS (n=264) DUPIXENT 300 mg Q2W + TCS (n=89) patients achieved clinically meaningful improvement in pruritus with + TCS at 52 weeks, seen as early as 2 weekspatients achieved clinically meaningful improvement in DLQI + TCS at 52 weeks Wmkrm�gerx i�gegy ew monotherapyRapid and sustained improvement IG , Investigator's Global ssessment; Q2W, once every 2 weeks.Emollient background regimen/therapy was required.Results depicted in graph were derived from a post-hoc analysis. P

4 ercent of patients achieving EASI-75 We
ercent of patients achieving EASI-75 Weeks48%13%3% 0124681216 P=0.0025 10 Placebo (n=460) DUPIXENT 300 mg Q2W (n=457) �3x P 100 8070 60 50 40 30 20 Weeks Placebo + TCS (n=264) DUPIXENT 300 mg Q2W + TCS (n=89) 6569 Percent of patients achieving EASI- 75 10 8070 60 50 40 30 20 381723 0 4 8 12 16 20 24 28 32 36 40 44 48 52 0 SOLO 1 and SOLO 2 trial design: Two randomized, placebo-controlled trials of identical design(SOLO 1, N=671 and SOLO 2, N=708) in adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment, randomized to DUPIXENT 300 mg Q2W or placebo for 16 weeks. The coprimary endpoints were at least 71% improvement at 16 weeks on the Eczema rea and Severity Index (E SI-71), and an Investigator's Global ssessment (IG ) score of 0 or 1 with a reduction from baseline of ≥2 points at 16 weeks.CHRONOS trial design: A randomized, double-blind, placebo-controlled trial of adults with moderate-to-severe atopic dermatitis (N=740), randomized to DUPIXENT 300 mg Q2W plus topical corticosteroids or placebo plus topical corticosteroids for 52 weeks. The coprimary endpoints were at least 75% improvement on the Eczema rea and Severity Index (E SI-71), and an Investigator's Global ssessment (IG ) score of 0 or 1 with a reduction from baseline of ≥2 points at 16 weeks. 106 patients were randomized to DUPIXENT 300 mg Q2W plus topical corticosteroids and 311 patients were randomized to placebo plus topical corticosteroids for 52 weeks. CHRONOS: Patients achieving EASI-75 Pooled SOLO and : Patients achieving EASI-10,b texmirxw eglmizih ≥;9) mqtvsziqirx mr piwmsr ixxirx erh wizivmxy at 16 weekstexmirxw eglmizih ≥;9) mqtvsziqirx mr piwmsr ixxirx erh wizivmxy + TCS at 52 weeks patients achieved an IGA score of 0 or 1 with a vihygxmsr sj ≥6 tsmrxw at 16 weeksMr WSPS 10 9127) erh 7;2=) sj HYTMXIRX

5 texmirxw eglmizih ≥;9)improvement in l
texmirxw eglmizih ≥;9)improvement in lesion extent and severity and an IG 0 or 1, respectively, vs 14.7% and 10.3% of placebo patientsMr WSPS 60 8826) erh 7:21) sj HYTMXIRX texmirxw eglmizih ≥;9)improvement in lesion extent and severity and an IG 0 or 1, respectively, vs 11.9% and 8.1% of placebo patientsMr GLRSRSW0 7<2;) sj HYTMXIRX patients achieved IGA 0 or 1 vs 12.4% of placebo patientsThe measurement for significance at 4 weeks was a post-hoc analysis. 4 Type I ReceptorType II Receptor IL-4IL-4IL-13IL-4RIL-4RIL-13RDUPIXENTDUPIXENT DUPIXENT selectively inhibits the signaling subunit shared by the receptor complexes for IL-4 and IL-13, inhibiting signaling of these key drivers of atopic dermatitis 5 (N=480)SOLO CONTINUESOLO 1 and 2 responders (N=671)(N=708)SOLO 1 and SOLO 2replicated trials (N=325)CHRONOS(N=740)With TCSMonotherapy Open-label extension 16 weeks52 weeks Trial program for DUPIXENT The largest clinical trial program for atopic dermatitisRecruited patients had a long history of disease (mean: 26 years)along with high disease burden5,6,9E SI, Eczema rea and Severity Index; TCS, topical corticosteroids. DUPIXENT + TCS in patients inadequately controlled with cyclosporine or for whom it is medically inadvisable; 16-week treatment period followed by a 12-week safety follow-up period.The DUPIXENT Phase 3 Trial program enrolled above worldwide, both as monotherapy and with TCSExtensive lesion severity, mean E SI score of ~33 out of 72Intense pruritus: average peak severity of 7 out of 10Large body surface area affected, mea n 50%Quality of life strongly impacted: Dermatology Life Quality Index, mean score of 14 In a study of 380 adult patients Patients with moderate-to-severe atopic dermatitis present with a high level of disease burdenThese results are patient-reported measures collected at screening for all randomized patients who entered a phase 2b clin

6 ical trial of dupilumab for the treatmen
ical trial of dupilumab for the treatment of moderate-to-severe atopic dermatitis for adults who had documented recent history (within 6 months) of inadequate response to topical corticosteroid treatment.* Measured b�y HADS- A - HADS- D 8Relentless pruritus lasting ≥12 hrs/day in 63%Lesionscausedpain and discomfortin 75%Affected social and leisure activities in 44%Symptoms of anxiety or depression*felt by 43%Disrupted sleep5 to 7 nights a week in 55%Loss of work productivity “frequently” or “always” in 46%     \r\n \r\f  
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 \b \b\r\f 3 Atopic dermatitis is a chronic disease driven by tivwmwxirx yrhivpymrk mr�eqqexmsrIL-4 and IL-13 are key Type 2 (including Th2) cytokines of atopic dermatitis that qshypexi xli mqqyri viwtsrwi0 hvmzi tivwmwxirx mr�eqqexmsr0 erh wsvwir fevvmAdapted from: J Allergy Clin Immunol. 2011;131(2):324-336; Guttman-Yassky E et al. J Allergy Clin Immunol.2011;127(6):1420-1432; Guttman-Yassky E et al. MPs, antimicrobial peptides; CCL, chemokine ligand; DC, dendritic cell; IFN-interferon gamma; IL, interleukin; ILC, innate lymphoid cell; LC, Langerhans cell; Th, T-helper cell; TSLP, thymic stromal lymphopoietin.Wyfgpmrmgep mr�eqqexmsr mw epweyw tviwirx xlvsyklsyx xli fshy0 izir mr INDICATIONDUPIXENT is indicated for the treatment of moderate-to-severe atopic dermatitis in adult patientswho are candidates for systemic therapy. CONTROLSee the evidence of long-termTheFIRST BIOLOGICforadults withmoderate-to-severeATOPIC DERMATITI