Establishing clinical equlvalence

PHASE lll CLlNlCAL STUDY

STUDY DESlGN1

N=544 patients with moderate to severe RA, despite MTX treatment

Baseline to
Week 52

Phase lll study; patients randomised (1:1) to lmraldiTM or reference adalimumab (40 mg/0.8 ml injections EOW). At Week 24, patients in latter arm were re-randomised (1:1) to continue reference adalimumab or transitioned to lmraldiTM (adalimumab)  (40 mg/0.8 ml injections EOW)

Primary endpoint: ACR20 at Week 24
Secondary endpoints: Additional efficacy analysis (ACR50, ACR70, DAS28-ESR, and EULAR response), Safety and immunogenicity up to week 52

Abbreviations: ACR20, American College of Rheumatology 20% improvement criteria; EOW, every other week; MTX, methotrexate; PK, pharmacokinetics; RA, rheumatoid arthritis; rADL, reference adalimumab.

REFERENCES

lmraldi™ (adalimumab) controlled disease activity as well as reference adalimumab1

Comparable ACR20 response to reference adalimumab up to Week 24

  • The difference in ACR20 response rate of per-protocol seta was 0.1%, (95% Cl -7.83, 8.13), which was well contained within the predefined equivalence margin (± 15%) at Week 24
  • Comparable efficacy was observed for the secondary endpoints (ACR50 and ACR70)

Adapted from: Weinblatt ME et al. Arthritis Rheumatol. 2018.

a The per-protocol set was the primary analysis set and included patients who completed the week 24 visit, had adherence in the range of 80–120% of the expected number of study drug and MTX doses, and were without any major protocol deviations that could affect the efficacy assessment.

Abbreviations: ACR20, American College of Rheumatology 20% improvement criteria; ACR50, American College of Rheumatology 50% improvement criteria; ACR70, American College of Rheumatology 70% improvement criteria; rADL, reference adalimumab; Cl, confidence interval.

Comparable response rates up to Week 521,2a

  • ACR response rates were maintained after transition from reference adalimumab to lmraldiTM at Week 24
  • Results for the rADL/lmraldiTM and the rADL/rADLb groups were comparable up to Week 52
  • Efficacy between the lmraldiTM/lmraldiTM and rADL/rADL groups was comparable throughout the study
  • Efficacy was maintained from Week 24 to Week 52 across all treatment groups

Adapted from: Weinblatt ME et al. Arthritis Rheumatol. 2018.

a The full-analysis set comprised all randomized patients (intent-to-treat principle); patients who were inadvertently randomized were excluded from this analysis, provided that they did not receive study drug.

b Patients who initially received rADL and continued to do so after re-randomisation at Week 24.

Abbreviations: ACR20, American College of Rheumatology 20% improvement criteria; ACR50, American College of Rheumatology 50% improvement criteria; ACR70, American College of Rheumatology 70% improvement criteria; Cl, confidence interval; rADL, reference adalimumab.

Comparable DAS28 response to reference adalimumab at Week 241

  •  Mean change from baseline to Week 24 in DAS28 was comparable between lmraldi™ (adalimumab) and reference adalimumab
  • The least squares mean for the treatment difference in DAS28 at Week 24 was −0.04 p= 0.69, (95% Cl −0.26, 0.17), which was contained within the predefined equivalence margin (−0.6 to 0.6)1

Adapted from: Weinblatt ME, et al. Arthritis Rheumatol. 2018;70(6):832-840.

Abbreviations: Cl, confidence interval; DAS28, Disease Activity Score in 28 joints based on the erythrocyte sedimentation rate; rADL, reference adalimumab.

Patients who switched to lmraldi™ (adalimumab) maintained DAS28 outcomes2

  • lmprovement in disease activity was maintained when patients switched from reference adalimumab to lmraldiTM

The least squares mean for the treatment difference in DAS28 at Week 52 for rADL/rADL vs rADL/Imraldi™ was - 0.08 (95% CI: - 0.40, 0.24) p= 0.61, which was contained within the predefined equivalence margin (−0.6 to 0.6).

Adapted from: Weinblatt ME, et al. 2018.

a Patients who initially received rADL and continued to do so after re-randomisation at Week 24.

Abbreviations: DAS28, Disease Activity Score in 28 joints based on the erythrocyte sedimentation rate; rADL, reference adalimumab.

lmraldi™ (adalimumab) slowed radiographic progression similarly to reference adalimumab1,2

Radiographic progression was comparable up to Week 52

  • Radiographic progression was minimal and comparable across the treatment arms for lmraldi™  (adalimumab) and reference adalimumab

Adapted from: Weinblatt ME, et al. 2018.

a Patients who initially received rADL and continued to do so after re-randomisation at Week 24.

Abbreviations: mTSS, Modified total Sharp/van der Heijde score; rADL, reference adalimumab.

Comparable safety profile to reference adalimumab2

Comparable safety profile demonstrated across multiple parameters up to Week 521

  • lncidence of treatment-emergent adverse events, severe adverse events, injection site reactions and anti-drug antibodies were comparable for both treatment groups1,3
  • For full safety information, please refer to the lmraldiTM (adalimumab) Summary of Product Characteristics here
Treatment emergent adverse events reported in ≥2% of patients in either treatment group at up to Week 52

Adapted from: CHMP Assessment Report, 2017.

Abbreviations: rADL, reference adalimumab.