ABSTRACT: BOSTON, MA — Alexion Pharmaceuticals, Inc. reported that rheumatoid arthritis patients receiving a single dose of its anti-inflammatory complement inhibitor 5G1.1 showed a significant reduction in the signs and symptoms of the often painful joint condition as compared to placebo-treated patients.
The completed clinical trial examined the safety and biologic activity of 5G1.1 in 42 patients with mild to moderate rheumatoid arthritis, each of whom received a single dose of the drug. The company presented data at the 63rd annual American College of Rheumatology (ACR) meeting demonstrating that 50 percent of the patients (n=6) who received a single 8 mg/kg dose achieved an ACR20 score, as compared to 10 percent of the patients (n=10) treated with placebo (P=.07). ACR20 score means that a patient had a 20 percent improvement in tender and swollen joint count plus 20 percent improvement in at least three of five of the following criteria: patient pain assessment, physician global assessment, patient global assessment, patient self-assessed disability and acute phase reactant. It was previously reported, in April 1999, that the single 8 mg/kg dose resulted in a 30 percent decrease (P less than .05) in the levels of the acute phase reactant C-reactive protein, an objective measure of disease activity.
“The study’s results demonstrate that rheumatoid arthritis patients who received a single dose of Alexion’s anti-inflammatory C5 Complement Inhibitor drug, 5G1.1, felt less pain and were better able to function than those patients receiving placebo,” said Dr. Leonard Bell, President and Chief Executive Officer of Alexion. “Further, the clinical measurement in the current study, ACR20 score, which is the same endpoint of our ongoing Phase II safety and efficacy trial with 5G1.1, was met.”
The report, entitled “A Single Dose, Placebo Controlled, Double Blind, Phase I Study of the Humanized Anti-C5 Antibody h5G1.1 in Patients with Rheumatoid Arthritis,” is based on a clinical trial conducted by investigators at North Shore Hospital, Gainesville Clinical Research Center and University of Alabama in collaboration with Alexion. Dr. Christopher Mojcik, a clinical rheumatologist and Senior Director of Clinical Development at Alexion, presented the clinical data.
“In follow-up to this initial single dose 5G1.1 trial in rheumatoid arthritis patients, we are currently enrolling up to 200 patients in a Phase II efficacy trial employing multiple doses of 5G1.1 in rheumatoid arthritis patients,” commented Dr. Mojcik. “We are examining the safety and efficacy of multiple doses of 5G1.1 with the primary efficacy endpoint as the ACR20 score.”
It is estimated that more than two million patients are affected by rheumatoid arthritis, a disease in which the immune system attacks multiple joints as well as the whole body. This chronic immune attack frequently involves multiple organs in the body leading to the onset of fatigue, severe joint destruction, pain and disfigurement.
Dr. Jacques Caldwell of Gainesville Clinical Research Center, a principal investigator in the completed trial and ongoing Phase II trial, commented, “In my experience, inhibition of the complement pathway is a unique approach to treating rheumatoid arthritis. Hopefully, these early results will be confirmed by the ongoing studies in a larger patient cohort.”
Alexion’s C5 complement inhibitors are designed to selectively block the production of inflammation-causing proteins in a process of the human immune system known as the complement cascade. Alexion believes that selective suppression of this immune response will provide a significant therapeutic advantage relative to existing therapies. Because of the generally beneficial effects of the components of the complement cascade prior to C5 and the greater inflammatory disease-promoting effects of the cleavage products of C5, the company has identified C5 as a potentially effective anti-inflammatory drug target. The first two C5 Inhibitors, 5G1.1 and 5G1.1-SC, specifically and tightly bind to C5 blocking its cleavage into harmful byproducts and are designed to inhibit subsequent damage from the inflammatory process. 5G1.1 is currently being tested in Phase II safety and efficacy trials in rheumatoid arthritis and membranous nephritis patients.
Source: Alexion Pharmaceuticals, Inc.