SAT0240 Phase 3 trial results with blisibimod, a selective inhibitor of B-cell activating factor, in subjects with systemic lupus erythematosus (SLE)

• Published in: Annals of the rheumatic diseases Vol. 76; no. Suppl 2; p. 864
• Main Authors: Merrill, J, Martin, RS, Shanahan, WR, Scheinberg, M, Kalunian, K, Wofsy, D
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Limited 01.06.2017
• Subjects: Anti-DNA antibodies; Antimalarial agents; Antiphospholipid antibodies; BLyS protein; Cardiolipin; Clinical trials; Complement component C3; Complement component C4; Corticosteroids; Diarrhea; Erythema; Immunoglobulin G; Injection; Lupus; Lymphocytes B; Patients; Phospholipids; Population studies; Prednisone; Proteinuria; Respiratory tract diseases; Response rates; Stockholders; Systemic lupus erythematosus; Urinary tract
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2017-eular.2400

BackgroundTargeted, biologic inhibitors of B-cell Activating Factor (BAFF) have been evaluated in Phase 3 trials in over 5000 patients with SLE. Post hoc analyses of these studies identify lower placebo response and greater treatment effect using more stringent endpoints in patients entering with higher disease activity, greater corticosteroid doses, and/or anti-double-stranded DNA (dsDNA) and low complement C3 or C41,2.ObjectivesThe Phase 3 CHABLIS-SC1 trial evaluated blisibimod, an inhibitor of B-cell activating factor (BAFF), in a “responder population” identified from prior studies with this drug class.Methods442 SLE patients with anti-nuclear antibodies or anti-dsDNA, SELENA-SLEDAI score ≥10 on standard of care medications were randomized to receive weekly subcutaneous blisibimod (200 mg) or placebo. Corticosteroid taper was encouraged from Week 8 with the goal to reach ≤7.5 mg prednisone/day. The primary endpoint at Week 52 was the SLE Responder Index-6 (SRI-6): ≥6-point improvement in SELENA-SLEDAI, no new BILAG 1A or 2B domain scores, and <0.3-point increase in Physician's Global Assessment.ResultsThis study did not meet its primary endpoint at Week 52. Response rates to blisibimod were equivalent to past trials of BAFF inhibitors, but the placebo response was greater. A slightly higher proportion of subjects on blisibimod met the SRI-6 and SRI-4 criteria at most timepoints and more blisibimod-treated subjects achieved corticosteroid taper to prednisone ≤7.5 mg/day from Week 40 through Week 52 (p=0.04 at Week 44). Reductions in peripheral B cell lineages, anti-dsDNA, anti-phospholipid antibodies, and serum immunoglobulins, and increases in complement C3 and C4 were observed with blisibimod (see Table).Blisibimod was well-tolerated. The most common adverse events were upper respiratory tract infection (10.6% vs 14.3% on placebo), urinary tract infection (6.9% vs 10.7%), injection site erythema (7.8% vs 2.0%), injection site reaction (7.3% vs 2.6%), and diarrhea (7.3% vs 2.6%).Table of ResultsBlisibimod (N=245)Placebo (N=197) Disease characteristics at baselineSELENA-SLEDAI mean score13.413.5Low C3/C4 & anti-dsDNA, %62.461.7Proteinuria ≥0.5 g/g, %32.727.9Mean prednisone dose, mg15.615.6Oral immunosuppressant use, %42.441.6Antimalarial use, %61.262.2Results at Week 52 (*p<0.05, **p<0.01)SRI-6 (primary), %46.942.3SRI-4, %56.752.0Taper to ≤7.5 mg prednisone/day, %23.316.9Total B cell change from baseline, counts-3.30**-1.58Anti-dsDNA change from baseline, IU-134.8-75.5C3 and C4 change from baseline, mg/dL0.11**, 0.03**0.03, -0.002Anticardiolipin IgG % change from baseline-12.7*9.3ConclusionsWith a deliberate focus on a “responder population” for whom lower placebo rates were observed in previous trials, much higher placebo response rates were observed in the CHABLIS-SC1 trial. Modest benefits of blisibimod were observed on serological effects and corticosteroid tapering.References van Vollenhoven RF et al. Ann Rheum Dis. 2012;71:1343.Merrill JT et al. Ann Rheum Dis. 2016;75(2):332–40. Disclosure of InterestJ. Merrill Grant/research support from: BMS, GSK, Consultant for: Anthera, GSK, EMD Serono, Lilly, Astra Zeneca, BMS, UCB, Celgene, Biogen, R. Martin Shareholder of: Anthera, Employee of: Anthera, W. Shanahan Shareholder of: Anthera, Employee of: Anthera, M. Scheinberg Consultant for: GSK,Pfizer, Janssen, Genzyme,Anthera, Novartis, Speakers bureau: GSK,Pfizer, Janssen, Genzyme,Anthera, Novartis, K. Kalunian Grant/research support from: GSK, Celgene, UCB, Consultant for: Anthera, Genentech, BMS, Lilly, Biogen, Shire, Exagen, D. Wofsy Consultant for: Anthera, Genentech, Amgen, GSK