medwireNews: Namilumab induces a rapid and sustained clinically significant response in patients with moderate-to-severe rheumatoid arthritis (RA), with a favorable tolerability profile, show results of the phase II NEXUS trial.
Peter Taylor (University of Oxford, UK) and co-investigators explain that namilumab is “an immunoglobulin G1 monoclonal antibody that binds with high affinity to granulocyte-macrophage colony-stimulating factor (GM-CSF),” potently neutralizing the protein that is “aberrantly overproduced” in RA.
They say their double-blind, placebo-controlled study “demonstrates the benefit of inhibiting macrophage activity targeting the GM-CSF for RA.”
The drug was evaluated in 108 European and Japanese patients (mean age 48 years, 78% women) with moderate-to-severe RA (DAS28-CRP≥3.2), at least four swollen joints, and a visual analog scale pain score of more than 40 mm who had an inadequate response to methotrexate or anti-tumor necrosis factor therapy.
At baseline, average DAS28-CRP scores were similar (5.62–5.71) among the participants randomly assigned to receive placebo (n=27), and those assigned to namilumab 20 mg (n=28), 80 mg (n=25), or 150 mg (n=28), each given at baseline and weeks 2, 6, and 10.
By week 12, all study groups had experienced a dose-dependent reduction in DAS28-CRP from baseline, but the difference in the magnitude of reduction relative to placebo was only significant for patients who received namilumab 150 mg.
In this group, the reduction in DAS28-CRP was significant from week 2 onwards and increased with time, such that by week 12 patients who received namilumab 150 mg had a 0.92-point greater least-squares mean reduction in DAS28-CRP from baseline than those who received placebo (reductions of 1.69 vs 0.77 points).
Patients who received namilumab 150 mg were also significantly more likely to achieve DAS28-CRP remission (≤2.6) or an ACR50 response than those who received placebo, at 26.9% and 42.9% versus 9.0% and 15.0%, respectively.
And the researchers note that the number of participants attaining each of these responses had not plateaued by week 12, “which suggests that peak efficacy might not have been achieved.”
Treatment-emergent adverse events (AEs) were experienced by 55.6% of patients in the combined namilumab groups and 51.9% of those in the placebo group, with nasopharyngitis, dyspnea, bronchitis, and headache most commonly reported.
Few patients experienced AEs of special interest that could be suggestive of pulmonary alveolar proteinosis, and following review, all of the suggestive cases were given an alternative diagnosis.
Writing in Arthritis Research & Therapy, Taylor and co-authors conclude that the “150-mg dose of namilumab should be used to offer maximum efficacy to patients, with acceptable safety,” in future clinical trials.
They add: “From a manufacturing point of view and tolerability for the patient as a subcutaneous injection, 150-mg dose is the maximum feasible dose at the current concentration of the antibody as the investigational product.”
By Laura Cowen
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