Bristol-Myers Squibb Company and Alder Biopharmaceuticals announced that new data from a dose-ranging phase 2a trial support further development of BMS-945429/ALD518, an investigational monoclonal antibody directed against interleukin-6 (IL-6), as a potential treatment for rheumatoid arthritis (RA).

According to a company release, the phase 2a data will be presented in a scientific session on June 18, 2010, at the Annual Congress of the European League against Rheumatism (EULAR).

The 16-week phase 2a study evaluated the safety and efficacy of BMS-945429/ALD518 in 132 patients with RA inadequately controlled with methotrexate. Patients were randomized to receive intravenous infusions of 80 mg, 160 mg or 320 mg of BMS-945429/ALD518 or placebo once every 8 weeks, for a total of two doses. Efficacy was measured by ACR scores, a standardized measure of percentage improvement in RA signs and symptoms. All three treatment groups met the primary endpoint of statistically significant improvements in the ACR20 score over placebo at Week 12. At Week 16, ACR20 responses were observed in 75% - 82% of subjects receiving 80, 160 and 320 mg doses versus 36% of subjects receiving placebo; ACR50 responses were achieved in 41% - 50% of subjects receiving BMS-945429/ALD518 versus 15% of subject receiving placebo; and ACR70 responses were noted in 22% - 43% of subjects receiving BMS-945429/ALD518 versus 6% of subjects receiving placebo.

The most commonly reported adverse events were increases in liver enzymes (17% in BMS-945429/ALD518 versus 0% in placebo), and these were most frequent in the 320 mg dose group. Four patients discontinued study drug due to liver enzyme abnormalities. Transient neutropenias and increases in cholesterol were also observed in all dose groups. No serious infections, infusion reactions or immunogenicity were observed.

"BMS-945429/ALD518 is one of the first monoclonal antibodies targeted at the IL-6 cytokine to show clinical activity in patients with rheumatoid arthritis, thus providing proof of concept," said Philip Mease, M.D., investigator, Swedish Hospital Clinical Research Division, Seattle, Washington. "I look forward to the next phase of clinical development that will provide additional understanding of the efficacy and safety profile of this antibody."

Based on this data, Bristol-Myers Squibb and Alder, under a collaboration agreement signed in November 2009, will continue to pursue development of BMS-945429/ALD518 in rheumatoid arthritis. Under the collaboration agreement, Alder granted to Bristol-Myers Squibb worldwide exclusive rights to develop and commercialize BMS-945429/ALD518 for all potential indications, except cancer.

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases.

Alder Biopharmaceuticals Inc. uniquely identifies, develops and manufactures novel antibody therapeutics to alleviate human suffering in the autoimmune and inflammatory disease areas.