Biogen Idec's Baminercept, the First lymphotoxin-b PATHWAY Inhibitor in development, Shows Promise in Patients with Rheumatoid Arthritis
Investigational Compound Designed to Disrupt Autoimmune Cascade
BOSTON, MA - November 9, 2007 -- Biogen Idec today presented results from its Phase IIa trial of baminercept (LTßR-Ig or BG9924), the first dual-mechanism, lymphotoxin-b (LT-b) and LIGHT pathway inhibitor in development for the treatment of autoimmune diseases, including rheumatoid arthritis (RA). The data suggest clinically meaningful improvements in American College of Rheumatology (ACR) scores and individual core set measurements in patients with RA who received baminercept compared with placebo. Results from the Phase IIa trial were presented at ACR's 73rd Annual Meeting in Boston.
ACR score improvements persisted for up to eight weeks following the final study dose and were seen in patients given 1.0 mg/kg or 3.0 mg/kg once a week subcutaneously for four weeks, the two highest dose groups in the study. The most common adverse event was headache and no serious adverse events attributed to the compound were reported during the study period. Safety results support the continued development of baminercept.
"Pre-clinical studies suggest that baminercept blocks an underlying disease mechanism associated with inflammation," said Evan Beckman, Senior Vice President of Immunology Research and Development at Biogen Idec. "Autoimmune disorders that may be influenced by this mechanism include multiple sclerosis, lupus and Crohn's disease.We are encouraged that the results of this trial suggest potential benefits of targeting the LT-b pathway in developing a new RA treatment option."
Based on the results of this Phase IIa study, Biogen Idec has initiated two Phase IIb trials to study baminercept in combination with methotrexate in patients with moderate to severe RA who had an inadequate response to treatment with a DMARD therapy (disease-modifying antirheumatic drug) or a TNF inhibitor (biologic therapies that target the TNF pathway).
Rheumatoid Arthritis and the LT-b Pathway
In patients with RA, certain immune cells malfunction and attack the joints, causing painful and chronic inflammation as well as destruction of cartilage, tendons and bones. As in other autoimmune diseases, the immune system mistakes healthy cells for foreign invaders. Though the exact cause of RA is unknown, new research is uncovering the immunologic and genetic factors that play important roles in triggering and perpetuating inflammation of the joints.
As shown in preclinical studies, baminercept is thought to inhibit the function of LTa1? and LIGHT, two critical components of the LT-b pathway implicated in the progression of RA and other autoimmune diseases. These diseases are in part characterized by the inappropriate emergence of organized immune cell collections, or lymphoid structures, in a variety of tissues. Baminercept is thought to act by inhibiting the formation and maintenance of out-of-place, or 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 LTa1? and LIGHT ligands, baminercept may help restore a normal immune environment.
The LT-b pathway was discovered at Biogen Idec, and baminercept is a wholly-owned Biogen Idec molecule that was discovered in collaboration with academic scientists. Baminercept is one of several programs in the company's research and development efforts in rheumatology.
Phase IIa Data Results
The Phase IIa blinded, multicenter, placebo-controlled trial was designed to assess the safety, pharmacokinetics, pharmacodynamics and efficacy of baminercept with methotrexate, a standard RA therapy, at different dose ranges. Patients (n=47) were randomized in a dose-escalating fashion to receive placebo or one of six doses of baminercept, ranging from 0.01 mg/kg to 3.0 mg/kg once weekly for four weeks, followed by eight weeks of observation. Patients had to have received methotrexate for at least three months prior to enrollment and continued to receive a stable dose of methotrexate throughout the study period.
Study results suggested improvement in the majority of ACR core set measurements (a series of standard measurement criteria for RA symptom and disease improvement) in patients given baminercept compared with placebo. At day 35, patients given baminercept showed an average 60 percent improvement from baseline in swollen joint count and 47 percent improvement in tender joint count, compared with 4.6 percent and 6.7 percent with placebo, respectively. Improvements in these ACR measures persisted for eight weeks after the final baminercept dose. Similar levels of improvements were observed at day 35 in several other standard markers of inflammation and disease progression. ACR scores and other measures improved in a dose dependent manner, with the greatest improvements reported in the groups receiving 1.0 mg/kg and 3.0 mg/kg.
The most common adverse event in patients receiving baminercept was headache. Transient mild-to-moderate flu-like symptoms were observed in 9 patients (25 percent) within 24 hours after the first dose of baminercept. However, these symptoms responded well to acetaminophen and tended not to recur with subsequent doses. No serious, drug-related adverse events were reported in this study.
About Biogen Idec
Biogen Idec creates new standards of care in therapeutic areas with high unmet medical needs. Founded in 1978, Biogen Idec is a global leader in the discovery, development, manufacturing, and commercialization of innovative therapies. Patients in more than 90 countries benefit from Biogen Idec's significant products that address diseases such as lymphoma, multiple sclerosis, and rheumatoid arthritis. For product labeling, press releases and additional information about the company, please visit www.biogenidec.com <http://www.biogenidec.com/> .
This press release contains "forward-looking statements" regarding Biogen Idec's development of baminercept that are based on current expectations and assumptions that are subject to risks and uncertainties. Only a small number of research and development programs result in commercialization of a product. Factors which could cause actual results to differ materially from Biogen Idec's current expectations include the risk that results observed in the Phase IIa trial may not be predictive of the results to be obtained in the additional studies that would be necessary to demonstrate baminercept to be safe and effective in the treatment of patients with RA. In addition, the company may not be able to meet applicable regulatory standards or regulatory authorities may fail to approve baminercept; and the company may encounter other unexpected hurdles. For further information regarding factors, risks and uncertainties relating to Biogen Idec's drug research and development and other activities, please refer to the filings Biogen Idec has made with the Securities and Exchange Commission, including the "Risk Factors" section of Biogen Idec's Quarterly and Annual Reports, copies of which may be obtained at www.biogenidec.com. Biogen Idec assumes no obligation to update and specifically disclaims any duty to update the information in this press release for any reason, except as required by law, even as new information becomes available or other events occur in the future. All forward-looking statements in this press release are qualified in their entirety by this cautionary statement.
Posted: November 2007