Biogen Idec (CAMBRIDGE, Massachusetts) announced results from its phase IIa trial of baminercept, the first dual-mechanism, lymphotoxin-β (LT-β) and LIGHT pathway inhibitor in development for the treatment of autoimmune diseases, including rheumatoid arthritis (RA). The data suggest clinically meaningful improvements in ACR scores and individual core set measurements in patients with RA who received baminercept compared with placebo.

ACR score improvements and other measures persisted for up to 8 weeks following the final study dose and were seen in patients given the highest doses of 1 mg/kg or 3 mg/kg. Study results suggested improvement in the majority of ACR core set measurements in patients given baminercept compared with placebo. At day 35, patients given the agent showed an average 60% improvement from baseline in swollen joint count and 47% improvement in tender joint count, compared with 4.6% and 6.7% with placebo, respectively. Improvements in these ACR measures persisted for 8 weeks after the final baminercept dose. No serious adverse events attributed to the compound were reported.

The phase IIa blinded, multicenter, placebo-controlled trial was designed to assess the safety, pharmacokinetics, pharmacodynamics, and efficacy of baminercept with methotrexate (MTX), at different dose ranges. Patients (N = 47) were randomized in a dose-escalating fashion to receive placebo or one of six doses of baminercept 0.01 mg/kg to 3 mg/kg once-weekly for 4 weeks, followed by 8 weeks of observation. Patients must have received MTX for at least 3 months prior to enrollment and continued to receive a stable dose of MTX throughout the study period.

Biogen has initiated two phase IIb trials to study baminercept in combination with MTX in patients with moderate-to-severe RA who had an inadequate response to treatment with DMARD therapy or TNF inhibitor.

Preclinical studies suggest that baminercept blocks the function of LTα1ß2 and LIGHT, two critical components of the LT-β pathway implicated in the progression of RA and other autoimmune disorders such as multiple sclerosis, lupus, and Crohn's disease. These diseases are in part characterized by the inappropriate emergence of lymphoid structures in a variety of tissues. Baminercept is thought to act by inhibiting the formation and maintenance of ectopic lymphoid structures implicated in the autoimmune disease cascade. In RA, aberrant immune effector cells may rely on these ectopic lymphoid structures present in inflamed joints to trigger and propagate the chronic inflammatory process. By blocking inappropriate signals from cell-surface LTα1ß2 and LIGHT ligands, the agent may help restore a normal immune environment.

The LT-β pathway was discovered at Biogen and baminercept is a wholly-owned Biogen molecule that was discovered in collaboration with academic scientists. The agent is one of several programs in the company's research and development efforts in rheumatology.