Background/Purpose : SM101, which represents the human soluble non-glycosylated version of the Fcγ receptor IIB, binds to the Fc part of autoimmune complexes and inhibits the binding of immune complexes to cell-standing Fcg receptors. It has undergone preclinical and clinical safety and efficacy investigation, with evidence of efficacy in primary immune thrombocytopenia. The mode of action could make SM101 a safe and effective treatment for systemic lupus erythematosus (SLE).

Methods: The objectives of this phase IIa randomised, double-blind, placebo-controlled parallel-group study were to evaluate the safety, tolerability and efficacy of placebo and 2 doses of SM101 (6mg/kg and 12mg/kg), randomised 1:2:2, in patients with SLE. The main inclusion criteria were a diagnosis of SLE, evidence of serological activity (high anti-dsDNA activity or low C3), and a SELENA-SLEDAI score ≥ 6 points, with stratification to include patients with lupus nephritis (LN). Concomitant immunosuppressive therapy with corticosteroids, mycophenolate mofetil (MMF) or azathioprine and adjuvant SLE medication were allowed at constant doses during the study. Eligible patients received an infusion of study drug once a week for the first 4 weeks; study duration was 24 weeks. Data were reviewed regularly by an independent safety monitoring board. Response was measured at 24 weeks according to the SLE Responder Index (combination of SELENA-SLEDAI response ≥ 4 points, no BILAG A or 2 x B flares and no PGA score worsening).

Results: Fifty one eligible patients, 14 with LN, from 8 European countries and Australia, were randomized and received at least one dose of active investigational drug or placebo. Concomitant medications were corticosteroids (96% of patients), MMF (45%), azathioprine (20%) or combinations thereof. Patient numbers per group and response rates are shown in Table 1. The SLE Responder Index response rate was twice as high in the SM101-treated patients compared with placebo, and response in patients with LN was proportionately greater. The response rate on SM101 remains the same after exclusion of 15 patients who received rescue medication. The main clinical drivers for response were improvement in arthritis and in skin eruption (present in 75% and 50% patients respectively) according to the BILAG scale. Both worsened or remained unchanged in placebo patients; in SM101-treated patients improvement or resolution occurred in 57% with arthritis and 45% with skin eruption. No safety signals which could be attributed specifically to SM101 were reported, and no serious adverse events were probably or possibly related to the drug. No anti-drug antibodies were detected.

Conclusion: The encouraging results of this early phase study indicate that the novel biological SM101 warrants further investigation as a treatment for patients with SLE, including patients with LN.

Table 1. Percentage of Patients Responding According to the SLE Responder Index and its Components

	ALL PATIENTS			PATIENTS WITH LN
	Placebo (n=11)	6mg/kg (n=22)	12mg/kg (n=18)	Placebo (n=3)	6mg/kg (n=6)	12mg/kg (n=5)
SLE   Responder Index	18%	36%	39%	0%	50%	60%
SELENA-SLEDAI   Reduction ≥ 4 Points	27%	41%	50%	0%	50%	80%
SELENA-SLEDAI   Reduction ≥ 6 Points	9%	14%	28%	0%	17%	60%
BILAG   No Worsening	91%	77%	100%	100%	83%	80%
PGA   No Worsening	55%	77%	89%	67%	67%	80%

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/sm101-a-novel-recombinant-soluble-human-fc%ce%b3iib-receptor-in-the-treatment-of-systemic-lupus-erythematosus-results-of-a-double-blind-placebo-controlled-multicenter-study/