Alexion Pharmaceuticals, Inc. announced preliminary results of its Phase IIb study of eculizumab in rheumatoid arthritis patients. The primary efficacy endpoint of the trial was the improvement in ACR20 score after a six-month treatment period. Results of the current trial indicate that the primary endpoint was achieved with statistical significance in one of the two drug treatment arms, the monthly dosing arm. These results are consistent with the positive observations obtained with the monthly dosing regimen in the previous Phase IIa rheumatoid arthritis trial announced in 2001.

This double-blind, randomized, placebo-controlled Phase IIb rheumatoid arthritis trial enrolled approximately 350 patients with chronic disease undergoing treatment with methotrexate or leflunomide. The trial consisted of one placebo and two drug treatment arms, and dosing was conducted over a six-month period. Monthly administration of eculizumab following an induction period was associated with a statistically significant, moderate improvement in the ACR20 score versus placebo at six months. Importantly, monthly therapy was also associated with evidence of a long-term anti-inflammatory effect, with a significant reduction in a key pre-specified objective measure of disease activity, ESR (erythrocyte sedimentation rate), at six months. The other drug treatment arm, biweekly administration of eculizumab following an induction period, was not associated with a significant improvement in ACR20 score. This trial confirms observations from the earlier Phase IIa eculizumab rheumatoid arthritis trial in which the same monthly eculizumab regimen was also associated with a statistically significant, moderate improvement in ACR20 score.

Eculizumab treatment appeared to be safe and well tolerated, with the most common adverse events being upper respiratory tract infection, headache and nausea. The most common serious adverse events were myocardial infarction, accidental injury and cerebral infarction. Serious and common adverse event rates appeared to be similar between placebo and eculizumab in the study population.

“These preliminary data build on the results from the earlier Phase IIa trial indicating that there is statistically significant improvement in clinical symptoms with eculizumab treatment in a broad rheumatoid arthritis population,” stated Dr Leonard Bell, CEO of Alexion. “As we continue to develop eculizumab in multiple clinical settings in which complement is known to contribute to disease, we are particularly encouraged by the significant anti-inflammatory effect and safety of eculizumab observed in this clinical trial. This is relevant to our studies of eculizumab in Paroxysmal Nocturnal Hemoglobinuria (PNH), which we have noted over the past year is the lead indication for eculizumab development.”

After completing the analysis of this Phase IIb rheumatoid arthritis trial, Alexion anticipates presenting the results at an upcoming scientific conference and determining its plans for eculizumab in rheumatoid arthritis.

ACR20 is a measure established by the American College of Rheumatology that requires a 20 per cent improvement in tender and swollen joint count plus a 20 per cent improvement in at least 3 of 5 of the following criteria: patient pain assessment, physician global assessment, patient global assessment, patient self-assessed disability and acute phase reactant.