Improvement in ACR response rates at 3 years1-3

*FUTURE 2 (PsA 1) was a multicenter, randomized, double-blind, placebo-controlled trial that evaluated 397 adult patients with active PsA (≥3 swollen and ≥3 tender joints) despite use of NSAIDs, corticosteroids, or DMARDs. Patients had a diagnosis for ≥5 years and received COSENTYX 75 mg (n=99), 150 mg (n=100), 300 mg (n=100), or placebo (n=98) subcutaneously at Weeks 0, 1, 2, 3, and 4, followed by the same dose every 4 weeks. Patients who received placebo were rerandomized to COSENTYX 150 mg or 300 mg every 4 weeks at Week 16 or Week 24 based on responder status. The primary end point was ACR20 response at Week 24. At baseline, up to 66% and 46% of patients had enthesitis or dactylitis, respectively. Approximately 1/3 of patients discontinued previous treatment with anti–TNF-α agents due to either lack of efficacy or intolerance (up to 3 different TNF-α inhibitors). Approximately 44% of patients were on concomitant methotrexate.1,2

ACR20 response up to 85% at 3 years3†

With COSENTYX 300 mg

Anti–TNF Naive Patients Achieved ACR Response Rates at 3 Years, 300 mg Dose Graph

FUTURE 2 uncontrolled exploratory analysis: As observed in a subgroup from baseline through 3 years.3,4

With COSENTYX 150 mg

Anti–TNF Naive Patients Achieved ACR Response Rates at 3 Years, 150 mg Dose Graph

FUTURE 2 uncontrolled exploratory analysis: As observed in a subgroup from baseline through 3 years.3,4

After Week 24, patients knew they were taking the active treatment but remained blind to the dose until after 1 year. At 1 year, patients were unblinded and the patients who benefited from the study treatment based on the investigator's clinical assessment continued to receive the same active dose as open-label treatment, and patients were assessed every 8 weeks through 2 years, and every 12 weeks through 3 years. As with other uncontrolled studies, this phase of the study has limitations (eg, no placebo comparisons and patients responding better are more likely to stay in the study over time).3,4

In the 300-mg arm, ACR20/50/70 response rates in the anti–TNF-α naive subgroup (n=67) (prespecified exploratory end points) were consistent through Week 156. At baseline, n=63 patients were anti–TNF-α naive in the 150-mg arm. ACR20/50/70 response rates were lower in the anti–TNF-α experienced subgroup, which comprised 1/3 of patients.1-4

All data presented are as observed; patients with missing data at a specific time point are not included in the analysis.1

COSENTYX 150-mg arm includes 18 patients who were up-titrated to 300 mg starting at Week 128, at the investigator’s discretion.3

ACR20 response regardless of MTX use at 3 years3‡

With COSENTYX 300 mg

Notable ACR Response Rates Regardless of MTX Use at 3 Years, 300 mg Dose Graph

FUTURE 2 uncontrolled exploratory analysis: As observed in a subgroup from baseline through 3 years.3,4

With COSENTYX 150 mg

Notable ACR Response Rates Regardless of MTX Use at 3 Years, 150 mg Dose Graph

FUTURE 2 uncontrolled exploratory analysis: As observed in a subgroup from baseline through 3 years.3,4

After Week 24, patients knew they were taking the active treatment but remained blind to the dose until after 1 year. At 1 year, patients were unblinded and the patients who benefited from the study treatment based on the investigator's clinical assessment continued to receive the same active dose as open-label treatment, and patients were assessed every 8 weeks through 2 years and every 12 weeks through 3 years. As with other uncontrolled studies, this phase of the study has limitations (eg, no placebo comparisons and patients responding better are more likely to stay in the study over time).3,4

Patients were allowed to stay on MTX (up to 25 mg/week) if the dose was stable for at least 4 weeks prior to randomization and they had to remain on a stable dose up to Week 52.1

All data presented are as observed; patients with missing data at a specific time point are not included in the analysis.1

COSENTYX 150-mg arm with MTX includes 14 patients who were up-titrated to 300 mg starting at Week 128, at the investigator's discretion. COSENTYX 150-mg arm without MTX includes 17 patients who were up-titrated to 300 mg starting at Week 128.3

At baseline, n=45 patients and n=55 patients were with and without MTX, respectively, in the 300-mg arm and n=46 patients and n=54 patients were with and without MTX, respectively, in the 150-mg arm.3

ACR response rates through 3 years regardless of anti-TNF experience

With COSENTYX 300 mg

Notable ACR Response Rates Regardless of Anti-TNF Experience at 3 Years, 300 mg Dose Graph

§FUTURE 2 uncontrolled exploratory analysis: As observed from baseline through 3 years.3,4

With COSENTYX 150 mg

Notable ACR Response Rates Regardless of Anti-TNF Experience at 3 Years, 150 mg Dose Graph

§FUTURE 2 uncontrolled exploratory analysis: As observed from baseline through 3 years.3,4

After Week 24, patients knew they were taking the active treatment but remained blind to the dose until after 1 year. At 1 year, patients were unblinded and the patients who benefited from the study treatment based on the investigator's clinical assessment continued to receive the same active dose as open-label treatment, and patients were assessed every 8 weeks through 2 years and every 12 weeks through 3 years. As with other uncontrolled studies, this phase of the study has limitations (eg, no placebo comparisons and patients responding better are more likely to stay in the study over time).3,4ll

All data presented are as observed; patients with missing data at a specific time point are not included in the analysis.1

COSENTYX 150-mg arm includes 31 patients who were up-titrated to 300 mg starting at Week 128, at the investigator's discretion.3

At baseline, 100 patients started in the 300-mg arm and 100 patients started in the 150-mg arm.1

llResults in the mixed population, defined as 2/3 anti–TNF-α naive and 1/3 anti–TNF-α experienced.1,2

Complete response rates in enthesitis over 3 years

Complete Response in Enthesitis Data at 3 Years, Graph

FUTURE 2 uncontrolled exploratory analysis: As observed in a subgroup from Week 2 through 3 years.3,4

After Week 24, patients knew they were taking the active treatment but remained blind to the dose until after 1 year. At 1 year, patients were unblinded and the patients who benefited from the study treatment based on the investigator's clinical assessment continued to receive the same active dose as open-label treatment, and patients were assessed every 8 weeks through 2 years and every 12 weeks through 3 years. As with other uncontrolled studies, this phase of the study has limitations (eg, no placebo comparisons and patients responding better are more likely to stay in the study over time).3,4

All data presented are as observed; patients with missing data at a specific time point are not included in the analysis.1

COSENTYX 150-mg arm includes 19 patients who were up-titrated to 300 mg starting at Week 128, at the investigator's discretion.3

At baseline, 64 patients and 56 patients had enthesitis in the 150-mg and 300-mg arm, respectively.1

#Patients with no enthesitis are defined as having a Leeds Enthesitis Index (LEI) score of 0 among patients with a score of 1 or more at baseline.1

Complete response rates in dactylitis over 3 years3**

Complete Response in Dactylitis Data at 3 Years, Graph

**FUTURE 2 uncontrolled exploratory analysis: As observed in a subgroup from Week 2 through 3 years.3,4

After Week 24, patients knew they were taking the active treatment but remained blind to the dose until after 1 year. At 1 year, patients were unblinded and the patients who benefited from the study treatment based on the investigator's clinical assessment continued to receive the same active dose as open-label treatment, and patients were assessed every 8 weeks through 2 years and every 12 weeks through 3 years. As with other uncontrolled studies, this phase of the study has limitations (eg, no placebo comparisons and patients responding better are more likely to stay in the study over time).3,4

All data presented are as observed; patients with missing data at a specific time point are not included in the analysis.1

COSENTYX 150-mg arm includes 14 patients who were up-titrated to 300 mg starting at Week 128, at the investigator's discretion.3

At baseline, 32 patients and 46 patients had dactylitis in the 150-mg and 300-mg arm, respectively.1

††Patients with no dactylitis are defined as having a Leeds Dactylitis Index (LDI) score of 0 among patients with a score of 1 or more at baseline.1

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ACR outcomes confirmed in FUTURE 5 at Week 24—the largest phase 3 study for a biologic in PsA to date5-11

In patients naive to TNF-α inhibitors

Up to 47% ACR50 response achieved5

TNF Naive Patients Achieved ACR 50 Response Rates up to 47% at 24 Weeks, Graph

In patients with anti–TNF-α exposure

Up to 37% achieved ACR50 results5

Anti-TNF Patients Achieved ACR 50 Response Rates up to 37% at 24 Weeks, Graph

See FUTURE 5 study design details

ACR50 in the mixed population5

Mixed Population Patients Achieved ACR 50 Response Rates up to 44% at 24 Weeks, Graph

ACR70 in the mixed population5

Mixed Population Patients Achieved ACR 70 Response Rates up to 26% at 24 Weeks, Graph

Patients who met escape criteria (less than 20% improvement in tender or swollen joint counts) at Week 16 were considered nonresponders at Week 20 and Week 24. Nonresponding patients receiving placebo were rerandomized to receive COSENTYX (either 150 mg or 300 mg every 4 weeks) at Week 16 but are still represented and imputed as nonresponders in the placebo arm. Results were analyzed using nonresponder imputation.5

COSENTYX inhibits progression of joint structural damage at 6 months as measured by mTSS2

Mean change from baseline in mTSS2

Significant Inhibition of Progression of Joint Structural Damage, Mean Change from Baseline

Placebo patients rescued at Week 16 had their value imputed using a linear mixed effects model.

150-mg No Load arm is not included because results were skewed by 2 outliers that showed improvements in radiographic status.

FUTURE 5 study design: FUTURE 5 was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial that evaluated 996 adult patients with active PsA. Patients were randomized to receive COSENTYX 150 mg without load (n=222), 150 mg with load (n=220), 300 mg with load (n=222), or placebo (n=332). Patients who received placebo were rerandomized to receive COSENTYX (either 150 mg or 300 mg every 4 weeks) based on responder status at Week 16 (nonresponders) or Week 24 (responders). The primary end point was the percentage of patients who achieved ACR20 response at Week 16 compared to placebo. Secondary end points included change in mTSS score at Week 24 from baseline, ACR50 response and proportion of patients with dactylitis and enthesitis at Week 16, and overall safety and tolerability. Study population was mixed: more than 2/3 of patients were anti–TNF-α naive and less than 1/3 were anti–TNF-α experienced.5

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COSENTYX maintained clearer skin at 2 years12

In the 300-mg arm (n=245) of the ERASURE study at Week 12*:

*In ERASURE, % of patients achieving an end point on 150 mg (n=245) vs placebo (n=248) at Week 12: PASI 75 (71 vs 4), IGA 0 or 1 (51 vs 2), and PASI 90 (39 vs 1). In FIXTURE, results on 300 mg (n=327) vs placebo (n=326) at Week 12: PASI 75 (76 vs 5), IGA 0 or 1 (62 vs 3), and PASI 90 (54 vs 2). In FIXTURE, results on 150 mg (n=327) vs placebo at Week 12: PASI 75 (67 vs 5), IGA 0 or 1 (51 vs 3), and PASI 90 (42 vs 2). At Week 12 in ERASURE, 65% of patients on COSENTYX 300 mg achieved IGA mod 2011 0 or 1 vs 2% of patients on placebo. All comparisons, P<0.0001. Results similar in FEATURE and JUNCTURE.2

In ERASURE, 59% of patients achieved PASI 90 on 300 mg vs 1% for placebo at Week 12.2

In the COSENTYX 300-mg treatment arm, 81% and 84% of patients in ERASURE and FIXTURE, respectively, who achieved PASI 75 at Week 12 sustained their response at Week 52. In the COSENTYX 150-mg treatment arm, 72% and 82% of patients in ERASURE and FIXTURE, respectively, who achieved PASI 75 at Week 12 sustained their response at Week 52.2

§In the COSENTYX 150-mg treatment arm (n=301), 76% of PASI 75 responders at Week 52 sustained PASI 75 at Week 104. At Week 52, 83% and 64% of patients in the 300-mg and 150-mg treatment arms, respectively, were PASI 90 responders; 71% and 45% of these patients, respectively, sustained their PASI 90 responses to Week 104.12

Study designs: The ERASURE and FIXTURE studies were multicenter, randomized, double-blind, placebo-controlled trials. ERASURE evaluated 738 adult patients who received COSENTYX 300 mg (n=245), COSENTYX 150 mg (n=245), or placebo (n=248). FIXTURE evaluated 1306 adult patients who received COSENTYX 300 mg (n=327), COSENTYX 150 mg (n=327), placebo (n=326), or a biologic active control (n=323). All patients were adults with moderate to severe plaque psoriasis who had a BSA ≥10%, PASI score ≥12, and IGA mod 2011 score ≥3 and were candidates for systemic therapy or phototherapy. Patients received treatment at Weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter. Patients randomized to receive placebo who were nonresponders at Week 12 and did not achieve PASI 75 were then rerandomized to receive COSENTYX 300 mg or 150 mg. All patients were followed for up to 52 weeks. Coprimary end points were PASI 75 and IGA 0 or 1 (clear or almost clear) response at Week 12, evaluated using NRI analysis.2,13,14

llThe ERASURE and FIXTURE extension is a multicenter, double-blind, randomized, uncontrolled, withdrawal study of COSENTYX in patients completing 52 weeks in the ERASURE and FIXTURE studies. Patients treated with COSENTYX 300 mg or 150 mg during the maintenance period in either the ERASURE or FIXTURE core studies and exhibited PASI 75 at Week 52 were eligible to be rerandomized 2:1 to continue the same COSENTYX dose—300 mg (n=363) or 150 mg (n=301)—or receive placebo (withdrawal from active treatment). Placebo patients who experienced relapse (defined as loss of >50% of maximum PASI improvement compared to baseline of the core study) at any visit were retreated with 5 weekly doses of COSENTYX 300 mg (n=136) or 150 mg (n=123), followed by 1 dose every 4 weeks. Primary end point was loss of PASI 75 response from baseline (Week 52) up to Week 68. Other end points included PASI 50/75/90 and IGA mod 2011 0 or 1 response rates over time, proportion of patients who relapsed, and PASI 50/75/90 response rates over time in patients who were retreated with COSENTYX 300 mg (n=181) or 150 mg (n=150) after relapse on placebo.12

Sustained response rates in the ERASURE/FIXTURE extension

PASI 75 and PASI 90 Response Rates at 2 Years, Graph Get your patients started on COSENTYX >

PsA safety profile1-3

Through Week 16

Cosentyx Adverse Reactions Table, PsA Clinical Trials Cosentyx Selected Adverse Events Table, PsA Program

*Adverse reactions listed are those occurring in at least 2% of patients in pooled secukinumab dose group up to Week 16.1

Includes 75-mg, 150-mg, and 300-mg doses (pooled outcome).1

Some patients were IV loaded (10 mg/kg at Weeks 0, 2, and 4).18

§The pivotal psoriatic arthritis program was FUTURE 1 and FUTURE 2.

In the FUTURE 2 open-label extension study

Adverse events of special interest through 3 years in patients with PsA3

Cosentyx Adverse Events in PsA Patients over 3 Years, Clinical Trials

COSENTYX 150-mg arm includes patients who were up-titrated to 300 mg at Week 128, at the investigator's discretion.3

§Includes 75-mg, 150-mg, and 300-mg doses (pooled outcome).3

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ACR=American College of Rheumatology; AS=ankylosing spondylitis; DMARDs=disease-modifying antirheumatic drugs; IGA=Investigator’s Global Assessment; mTSS=modified total Sharp score; MTX=methotrexate; NRI=nonresponder imputation; NSAIDs=nonsteroidal anti-inflammatory drugs; PASI=Psoriasis Area Severity Index; PsA=psoriatic arthritis; PsO=plaque psoriasis; TNF=tumor necrosis factor.

References: 1. Data on file. CAIN457F2312 Clinical Study Report. Novartis Pharmaceuticals Corp; October 2014. 2. Cosentyx [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2018. 3. Data on file. CAIN457F2312 (FUTURE 2): 3-Year Interim Report. Novartis Pharmaceuticals Corp; Sept 2017. 4. Data on file. CAIN457F2312 Interim Study Report. Novartis Pharmaceuticals Corp; November 2015. 5. Mease P, van der Heijde D, Landewé R, et al. Secukinumab improves active psoriatic arthritis symptoms and inhibits radiographic progression: primary results from the randomised, double-blind, phase III FUTURE 5 study. Ann Rheum Dis. 2018;77(6):890-897. 6. Antoni C, Krueger GG, de Vlam K, et al; for the IMPACT 2 investigators. Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial. Ann Rheum Dis. 2005;64(8):1150-1157. 7. Mease PJ, Gladman DD, Ritchlin CT, et al; for the Adalimumab Effectiveness in Psoriatic Arthritis Trial Study Group. Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial. Arthritis Rheum. 2005;52(10):3279-3289. 8. Mease PJ, Fleischmann R, Deodhar AA, et al. Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a Phase 3 double-blind randomised placebo-controlled study (RAPID-PsA). Ann Rheum Dis. 2014;73(1):48-55. ‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬ 9. Mease PJ, Kivitz AJ, Burch FX, et al. Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Arthritis Rheum. 2004;50(7):2264-2272. 10. Genovese MC, Mease PJ, Thomson GT, et al; M02-570 Study Group. Safety and efficacy of adalimumab in treatment of patients with psoriatic arthritis who had failed disease modifying antirheumatic drug therapy. J Rheumatol. 2007;34(5):1040-1050. 11. Ritchlin C, Rahman P, Kavanaugh A, et al; on behalf of the PSUMMIT 2 Study Group. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial. Ann Rheum Dis. 2014;73(6):990-999. 12. Data on file. Data Analysis Report: Study CAIN457A2302E1. Novartis Pharmaceuticals Corp; December 2015. 13. Data on file. AIN457A2302 Clinical Study Report. Novartis Pharmaceuticals Corp; September 2013. 14. Data on file. AIN457A2303 Clinical Study Report. Novartis Pharmaceuticals Corp; September 2013. 15. Data on file. 4-Year Interim Report: Study CAIN457A2304E1. Novartis Pharmaceuticals Corp; December 2016. 16. Data on file. CAIN457F2310 Abbreviated Clinical Study Report. Novartis Pharmaceuticals Corp; June 2017. 17. Data on file. CAIN457F2310 Clinical Study Report. Novartis Pharmaceuticals Corp; November 2014. 18. Data on file. AIN457F Summary of Clinical Safety in Psoriatic Arthritis. Novartis Pharmaceuticals Corp; February 2015.‬‬‬‬‬‬‬