PARIS, France—The lymphotoxin  (LT) β-receptor IgG1 (baminercept alfa, LTβR-Ig, BG9924) showed promising safety and efficacy results in phase II data reported at the 2008 EULAR meeting. Baminercept alfa is a construct that includes the human LTβR extracellular domain fused to the human IgG1 Fc domain. The construct binds to LT α1/ β2 and LIGHT ligands on activated lymphocytes and natural killer cells in order to block interactions between those ligands and their receptors on peripheral antigen-presenting and stromal cells.

The study, reported at EULAR by Megan Weaver, MD, of Biogen Idec, was led by Andrew Baldassare, of Rheumatology Consultants in St. Louis, Missouri.¹ It was a blinded, randomized, placebo-controlled, multicenter, phase IIa trial in 49 patients with moderate-to-severe RA whose disease had not been adequately controlled by treatment with more than one DMARD.

All patients continued stable MTX doses and were allowed concomitant RA therapy such as low-dose prednisone, NSAIDs, or hydroxychloroquine sulfate. They were randomly assigned to receive subcutaneous injections of baminercept alfa (0.01, 0.05, 0.1, 0.3, 1, or 3 mg/kg) or placebo once weekly for 4 weeks followed by 8 weeks of observation. The exploratory efficacy endpoints were DAS28, EULAR response, and ACR core set measures (swollen joint count, tender joint count, investigator and patient global assessments, Health Assessment Questionnaire, pain visual analog scale, C-reactive protein, erythrocyte sedimentation rate).

Adverse events rates were 55% in the placebo group versus 67% in the baminercept group, none of which were severe. There were no drug-related serious infections. According to Dr. Baldassare, the most common adverse effect in baminercept patients was headache, which occurred in 19% of treated patients versus 9% of placebo patients.

“At day 77, the mean change in DAS28 was -1.11 from baseline in baminercept alfa patients versus -0.315 in placebo patients,” Dr. Weaver reported. The mean change from DAS28 baseline was -1.434 with the 1 mg/kg dose and -2.441 with the 3 mg/kg dose. One third of the patients in the baminercept 3 mg/kg dose group achieved remission, compared with 0% of placebo patients. Dr. Weaver reported that similar patterns were observed in EULAR response and ACR core set measures. The researchers concluded, “Baminercept alfa is a promising novel therapeutic option for RA and warrants further study.”

Reference

1. Baldassare A, Fiechtner J, Filipowicz A, et al. Preliminary safety and efficacy of baminercept alfa (BG9924, LTβR-IG ) in the treatment of rheumatoid arthritis (RA). Presented at: EULAR 2008; June 11-14, 2008; Paris, France. Abstract OP-0122.