COSENTYX clinical trial end points

FUTURE 2

FUTURE 2 studied a mixed population of patients with PsA: 2/3 biologic-naive and 1/3 anti–TNF-α inadequate responders²

• ACR20 responses at Week 16 (NRI) in the mixed population were 57% (P<0.0001), 60% (P<0.0001), and 18%, respectively, for COSENTYX 300 mg (n=100), 150 mg (n=100), and placebo (n=98)^1,2

• The primary end point of ACR20 responses at Week 24 (NRI) was achieved by 54% of patients on COSENTYX 300 mg (n=100) (P<0.0001), 51% on COSENTYX 150 mg (n=100) (P<0.0001), and 15% on placebo (n=98)^1,2

• Skin lesions improved in patients with coexistent PsO who received COSENTYX (n=99) compared with placebo (n=43), as measured by the PASI^1,2

• Improvements in enthesitis and dactylitis scores were observed in the COSENTYX group compared with placebo at Week 24¹

FUTURE 5

FUTURE 5 studied a mixed population of patients with PsA: more than 2/3 biologic-naive and less than 1/3 anti–TNF-α inadequate responders¹⁰

JOINT¹⁰

ACR20 response rates (NRI) (primary end point) were:

• 63% for COSENTYX 300 mg (n=222) (P<0.0001)

• 56% for COSENTYX 150 mg (n=220) (P<0.0001)

• 27% for placebo (n=332)

ENTHESITIS¹⁰

Complete resolution (LEI=0) in patients with enthesitis at baseline (NRI):

• 56% for COSENTYX 300 mg (n=140)

• 55% for COSENTYX 150 mg (n=141)

• 35% for placebo (n=192)

DACTYLITIS¹⁰

Complete resolution (LDI=0) in patients with dactylitis at baseline (NRI):

• 66% for COSENTYX 300 mg (n=82)

• 57% for COSENTYX 150 mg (n=80)

• 32% for placebo (n=124)

SKIN¹⁰

Patients who achieved PASI 90 (NRI):

• 54% for COSENTYX 300 mg (n=110)

• 37% for COSENTYX 150 mg (n=125)

• 9% for placebo (n=162)

NAIL¹⁰*

Reduction in nail disease (mNAPSI as observed) response rates were^†:

• 51% for COSENTYX 300 mg (n=125)

• 53% for COSENTYX 150 mg (n=128)

• 11% for placebo (n=203)

MAXIMISE

MAXIMISE studied biologic-naive patients with PsA¹³

• The primary end point (ASAS20 responses at Week 12) was achieved by 63% of patients on COSENTYX 300 mg (n=164) compared with 31% for placebo (n=164) (MI; P<0.0001)¹³

• The key secondary end point, ASAS20 responses at Week 12 in patients on COSENTYX 150 mg, was achieved by 66% (n=157) (MI; P<0.0001)¹³

Data from the MAXIMISE trial, whose study design, patient population, and dosing regimen are consistent with those of FUTURE 2. In FUTURE 2, 20% of patients had spondylitis with peripheral arthritis.

*Nail data in PsA were consistent with those in the dedicated nail PsO study, TRANSFIGURE. Improvement from baseline NAPSI at Week 16 (primary end point) (repeated measures analysis) was 46.1% for COSENTYX 300 mg (n=63) and 11.7% for placebo (n=56) (P<0.0001).¹⁴

^†At baseline, mNAPSI scores were 18.0 and 17.8 in the 300-mg and 150-mg arms, respectively. At Week 16, mNAPSI scores were 8.8 and 8.4 in the 300-mg and 150-mg arms, respectively.¹⁰

Study designs

FUTURE 1 study design

FUTURE 1 was a multicenter, randomized, double-blind, placebo-controlled study that evaluated 606 patients with active PsA. Patients were treated with secukinumab 10 mg/kg IV treatment (or placebo) at Weeks 0, 2, and 4, followed by 75 mg or 150 mg subcutaneous COSENTYX treatment (or placebo) every 4 weeks. Patients receiving placebo were rerandomized to receive COSENTYX 75 mg or 150 mg every 4 weeks based on responder status at Week 16 or Week 24. Primary end point was the percentage of patients with ACR20 response at Week 24.^1,15

FUTURE 2 study design

FUTURE 2 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 subcutaneous COSENTYX 75 mg (n=99), 150 mg (n=100), 300 mg (n=100), or placebo (n=98) at Weeks 0, 1, 2, 3, and 4, followed by the same dose every 4 weeks thereafter. 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. Primary end point was the percentage of patients with ACR20 response at Week 24. Study population was mixed: 2/3 of patients were biologic-naive and 1/3 were anti–TNF-α inadequate responders.^1,2,16

FUTURE 3 study design

FUTURE 3 was a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, 3-year study that evaluated 414 adult patients with active PsA. Patients received subcutaneous COSENTYX 150 mg (n=138), 300 mg (n=139), or placebo (n=137) at Weeks 0, 1, 2, 3, and 4, followed by the same dose every 4 weeks thereafter. At Week 16, patients who received placebo were rerandomized to COSENTYX 150 mg or 300 mg every 4 weeks based on responder status at Week 16 (nonresponders) or Week 24 (responders). Primary end point was the percentage of patients with ACR20 response at Week 24. Autoinjector usability was also examined. Safety assessments included evaluation of AEs, SAEs, and immunogenicity.⁴

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 subcutaneous 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 150 mg or 300 mg every 4 weeks, based on responder status at Week 16 (nonresponders) or Week 24 (responders). Primary end point was the percentage of patients with ACR20 response at Week 16. Secondary end points included change in mTSS at Week 24 from baseline. Study population was mixed: more than 2/3 of patients were biologic-naive and less than 1/3 were anti–TNF-α inadequate responders (individual patients could have been exposed to up to 3 TNF-α inhibitors).^10,17

MAXIMISE study design

MAXIMISE was a randomized, double-blind, placebo-controlled, multicenter, 52-week study that evaluated 498 patients with active PsA and axial skeleton involvement (defined by BASDAI score ≥4, spinal pain VAS ≥40 0 to 100 mm scale) who had inadequate response to at least 2 NSAIDs for at least 4 weeks. Patients were randomized to receive subcutaneous COSENTYX 150 mg (n=165), COSENTYX 300 mg (n=167), or placebo (n=166) at Weeks 0, 1, 2, 3, 4, and 8. Primary end point was the proportion of patients with ASAS20 response at Week 12. After Week 12, patients who were placed in the placebo group at baseline were rerandomized to active treatment with COSENTYX 150 mg or 300 mg, administered every 4 weeks from Week 12 to Week 52 (last dose on Week 48) but remained blinded to dose.¹³

ACR=American College of Rheumatology; AE=adverse event; ASAS=Assessment of SpondyloArthritis international Society criteria; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; DMARDs=disease-modifying antirheumatic drugs; IV=intravenous; LDI=Leeds Dactylitis Index; LEI=Leeds Enthesitis Index; MI=multiple imputation; mNAPSI=modified Nail Psoriasis Severity Index; mTSS=modified Total Sharp Score; NAPSI=Nail Psoriasis Severity Index; NRI=nonresponder imputation; NSAIDs=nonsteroidal anti-inflammatory drugs; PASI=Psoriasis Area and Severity Index; PsA=psoriatic arthritis; PsO=plaque psoriasis; SAE=serious adverse event; TNF=tumor necrosis factor; VAS=visual analog scale.

Definitions

AE=adverse event; CV=cardiovascular; CYP3A4=cytochrome 3A4; CYP450=cytochrome P450; EAIR=exposure-adjusted incidence rate; ERA=enthesitis-related arthritis; IBD=inflammatory bowel disease; IV=intravenous; JPsA=juvenile psoriatic arthritis; MACE=major adverse cardiovascular event; MedDRA=Medical Dictionary for Regulatory Activities; PsO=plaque psoriasis; PTs=preferred terms; PY=patient-year; TB=tuberculosis.

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