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Abstract Number: 972

An Anti-CD28 Domain Antibody, Lulizumab, in Systemic Lupus Erythematosus: Results of a Phase II Study

Joan T. Merrill1, Diane E. Shevell2, Dominique Duchesne2, Miroslawa Nowak2, Sudeep Kundu2, Ihab G. Girgis2, Yanhua Sarah Hu2, Steven G. Nadler3, Subhashis Banerjee2 and John Throup2, 1Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, 2Bristol-Myers Squibb, Princeton, NJ, 3Immunosciences Translational Research, Bristol-Myers Squibb, Princeton, NJ

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: B cells, Lupus, T cells and systemic lupus erythematosus (SLE)

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Session Information

Date: Sunday, October 21, 2018

Session Title: 3S110 ACR Abstract: SLE–Clinical I: Clinical Trials (970–975)

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: The T cell costimulatory molecule, CD28, is critical for the activation of pathogenic T cells in autoimmune diseases.1,2 An anti-CD28 domain antagonist antibody, lulizumab pegol (lulizumab), was evaluated in a Phase 2 study in subjects with active systemic lupus erythematosus (SLE).

Methods: In a 24-week randomized, multicenter, double-blind study of subjects meeting the American College of Rheumatology criteria for SLE3,4, lulizumab was administered SC at doses of 1.25 mg every other week (EOW), 5 mg EOW, 12.5 mg EOW, or 12.5 mg weekly, or placebo (PBO) SC, on a background of standard of care (SOC) medications. Subjects were required to have elevated serum antinuclear antibodies, as well as BILAG “A” (severe) or “B” (moderate) arthritis and/or cutaneous manifestations, and SLEDAI ≥ 6 (at least 4 from clinical features). The maximum dose of corticosteroids could not exceed 30 mg/day of prednisone or equivalent at screening and no more than 10 mg/day at Day 1. The primary endpoint was the proportion of responders using the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) at Day 169 (Week 24).

Results: 349 subjects with SLE were randomized in five treatment arms (N=68-71/arm). There were no differences in the BICLA response rate at Day 169 (PBO = 59.2%, 1.25 mg EOW = 58.6%, 5 mg EOW = 57.4%, 12.5 mg EOW= 63.2% and 12.5 mg weekly=59.4%). Additional efficacy outcome measures (e.g. SRI-4, SRI-6, SRI-8, SLEDAI change from baseline, CLASI change from baseline, CLASI20 and CLASI50) also did not reveal significant differences between groups. Dose-dependent CD28 receptor occupancy correlated with drug exposure. Lulizumab treatment resulted in effects on T and B cell subsets and on markers consistent with the proposed CD28 mechanism of action. Lulizumab appeared to be well-tolerated overall (Table 1).

Table 1. Summary of safety over 24 weeks

PBO

(N =71)

1.25 mg EOW

(N=70)

5 mg EOW

(N=68)

12.5 mg EOW

(N=68)

12.5mg W

(N=69)

Deaths, n (%)

0

2 (2.9)

0

0

0

SAEs, n (%)

6 (8.5)

8 (11.4)

9 (13.2)

4 (5.9)

5 (7.2)

Related SAEs, n (%)

1 (1.4)

0

5 (7.4)

3 (4.4)

3 (4.3)

Discontinued due to SAEs, n (%)

1 (1.4)

5 (7.1)

4 (5.9)

2 (2.9)

3 (4.3)

Total subjects with AEs, n (%)

61 (85.9)

59 (84.3)

60 (88.2)

56 (82.4)

59 (85.5)

Discontinued due to AEs, n (%)

3 (4.2)

9 (12.9)

9 (13.2)

5 (7.4)

8 (11.6)

• 2 deaths in 1.25 mg EOW group were due to cerebral haemorrhage and SLE

Conclusion: There was no significant difference between lulizumab and placebo for the primary (BICLA response rate) or secondary endpoints at Week 24, although PD activity was observed. Lulizumab had a favorable safety profile.

References:

  1. Kow NY, Mak A. Clin Dev Immunol. 2013: 245928.
  1. Suchard SJ, Davis PM, Kansal S, et al. J Immunol. 2013; 191(9):4599–4610.
  1. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, et al. Arthritis Rheum 1982; 25:1271-1277.
  1. Hochberg MC. Arthritis Rheum 1997; 40:1725

Disclosure: J. T. Merrill, BMS, GSK, 2,BMS, GSK, UCB, Questcor, EMD Serono, Amgen, Celgene, Pfizer, RemeGen, Exagen, MedImmune, Lilly, Janssen, Xencor, Sanofi, Neovacs, Immupharma, Astellas, Glenmark, ILToo, 5,Have given talks for BMS but not for Speaker’s bureau, 9; D. E. Shevell, Bristol-Myers Squibb, 1, 3,Merck & Co., Inc., 1; D. Duchesne, Bristol-Myers Squibb, 1, 3; M. Nowak, Bristol-Myers Squibb, 1, 3; S. Kundu, Bristol-Myers Squibb, 3; I. G. Girgis, Bristol-Myers Squibb, 1, 3; Y. S. Hu, Bristol-Myers Squibb, 1, 3; S. G. Nadler, Bristol-Myers Squibb, 1, 3; S. Banerjee, Bristol-Myers Squibb, 1, 3; J. Throup, Bristol-Myers Squibb, 1, 3.

To cite this abstract in AMA style:

Merrill JT, Shevell DE, Duchesne D, Nowak M, Kundu S, Girgis IG, Hu YS, Nadler SG, Banerjee S, Throup J. An Anti-CD28 Domain Antibody, Lulizumab, in Systemic Lupus Erythematosus: Results of a Phase II Study [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/an-anti-cd28-domain-antibody-lulizumab-in-systemic-lupus-erythematosus-results-of-a-phase-ii-study/. Accessed February 1, 2023.
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