OP-0122 – Preliminary Safety and Efficacy of Baminercept Alfa (BG9924, LTBR-IG) in the Treatment of Rheumatoid Arthritis (RA)
Baldassare, Fiechtner, Filipowicz-Sosnowska, Jeka, Gorman, Weaver, Beckman. United States and Poland. [Sponsor, Biogen IDEC]
Objective
The aim of this study was to determine the safety and to explore the efficacy of lymphotoxin (LT) beta receptor IgG1 (baminercept alfa, LTBR-Ig, BG9924) in patients with RA. Baminercept alfa is composed of the extracellular domain of human LTBR fused to IgG1 Fc. It binds to LT alpha1/beta2 and LIGHT ligands, thus blocking interaction with their membrane associated receptors.
Methods
This was a blinded, randomized, placebo-controlled, multicenter, Phase 2a trial. Patients with moderate to severe RA who had had inadequate response to ≥1 DMARD continued their stable MTX dose, and were randomized to SQ injections of either baminercept alfa (0.01, 0.05, 0.1, 0.3, 1.0, or 3.0 mg/kg) or placebo every wk for 4 wks. Exploratory efficacy endpoints were DAS28, EULAR response and ACR core set measures.
Results
49 patients were randomized, and 47 received > 1 dose. Baseline demographic and disease activity characteristics were similar across treatment groups. 67% of baminercept alfa treated patients had adverse events (AEs) compared to 55% in the placebo group. No drug-related serious AEs, including serious infections, were reported. The most common AE in baminercept alfa patients was headache (7 [19%] patients vs 1 [9%] placebo patient). At Day 77, the mean change in DAS28 was -1.11 from BL in baminercept alfa patients vs -0.315 in placebo patients, with the 1.0 and 3.0 mg/kg dose group showing the greatest mean change from baseline with -1.434 and -2.441 respectively (Table). 33% patient in the 3.0 mg/kg dose group achieved remission compared to 0% placebo patients. Similar patterns were observed in EULAR response and ACR core set measures.
Efficacy |
Placebo |
0.01 |
0.05 |
0.1 |
0.3 |
1.0 |
3.0 |
|
# of Ptsa |
11 |
6 |
6 |
4 |
5 |
6 |
6 |
|
Baseline DAS28 |
5.706 |
5.087 |
5.803 |
5.148 |
5.198 |
5.890 |
5.858 |
|
Mean DAS Change |
-0.315 |
-0.488 |
-0.222 |
-1.354 |
-0.743 |
-1.434 |
-2.441 |
|
Mean% DAS change |
-5 |
-8 |
-2 |
-29 |
-12 |
-25 |
-43 |
|
Low Dis. Act. (%)b |
1 (9) |
0 |
0 |
2 (50) |
1 (20) |
1 (17) |
3 (50) |
|
Remission (% Pts)c |
0 |
0 |
0 |
2 (50) |
1 (20) |
1 (17) |
2 (33) |
aPts w/ efficacy at day 77; bDefined as DAS28 ≤3.2; cDefined as DAS28 <2.6.
Conclusion
Baminercept alfa was well tolerated. DAS28, EULAR responses and other efficacy measurements improved among patients who received baminercept alfa compared with placebo. Baminercept alfa is a promising novel therapeutic option for RA and warrants further study.
Editorial
Lymphotoxin is a novel therapeutic target and these preliminary data suggest that inhibition of lymphotoxin alpha and beta may have some efficacy in RA. Interestingly, etanercept also inhibits lymphotoxin and there has been debate over the years as to how much this effect of etanercept contributes to its efficacy in RA and in other inflammatory diseases. Thus far the data that lymphotoxin alpha and/or beta is an important player in the pathogenesis of RA are not compelling, but clinical trials such as this in a larger number of patients should provide a more definitive answer to this question.
