Promising Phase IIb Data On Clazakizumab In Patients With Moderate-To-Severe Rheumatoid Arthritis To Be Presented At The 2013 Annual Meeting Of The American College Of Rheumatology

Bristol-Myers Squibb Company (NYSE: BMY) and Alder Biopharmaceuticals today announced the presentation of efficacy and safety data from a Phase IIb dose-ranging study of subcutaneous (SC) clazakizumab in adults with moderate-to-severe rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX). Clazakizumab is a humanized anti-IL-6 monoclonal antibody that is directed against the IL-6 cytokine rather than its receptor. In the Phase IIb study clazakizumab doses ranging from 25-200 mg monotherapy and in combination with MTX were studied vs. MTX alone. Adalimumab in combination with MTX was included as an active reference arm. All clazakizumab treatment arms, alone or in combination with MTX, demonstrated efficacy in controlling the signs and symptoms of RA, and met the predefined primary endpoint of a higher ACR20 response rate vs. MTX alone after 12 weeks of treatment. All clazakizumab treatment groups were also associated with improved ACR 20/50/70 response rates and HAQ-DI scores vs. MTX at week 24. Rates of low disease activity and remission with clazakizumab plus MTX, as measured by DAS28 CRP, CDAI and SDAI criteria were numerically greater for clazakizumab at 12 and 24 weeks than the active comparator. The adverse event (AE) rates were similar across all clazakizumab arms. The most frequent AE for clazakizumab was dose-related injection site reactions. The most frequent reason for discontinuation due to AE in clazakizumab treated patients was laboratory abnormality, predominantly transaminase elevations, more frequent in MTX-containing arms. The most frequent serious adverse events (SAEs) were serious infections. Rates of serious infections were generally comparable for clazakizumab and adalimumab combination arms and were numerically greater than MTX alone. “There is a great need for additional disease-modifying therapies that can provide more patients with deep and sustainable remission, helping preserve function and limit further joint damage,” said Paul Emery, M.D., director of MSK Biomedical Unit at the Leeds Teaching Hospitals Trust in the United Kingdom. “Currently, less than 30% of RA patients experience sustained remission as defined by ACR criteria. Clazakizumab is an investigational therapy that neutralizes IL-6 signaling by blocking the IL-6 cytokine, and provides promising remission data that will need to be further investigated.” “Bristol-Myers Squibb has a long-standing commitment to immunoscience research and the development of innovative medicines for patients living with chronic immune-mediated diseases, such as RA,” said Brian Daniels, MD, senior vice president, Global Development and Medical Affairs, Research and Development, Bristol-Myers Squibb. “Despite the recent advances in the treatment of RA, more efficacious therapies are needed. The results of this study support the potential for clazakizumab to fulfill the need for new medicines that can help patients with RA achieve disease control and remission.” Bristol-Myers Squibb has exclusive worldwide rights to develop and commercialize clazakizumab for all indications outside of cancer under a collaboration agreement with its discoverer, Alder Biopharmaceuticals. “We are excited about the Phase IIb data and its confirmation of the earlier promise seen in Phase IIa,” added Randall Schatzman, PhD, president and CEO of Alder Biopharmaceuticals. “We look forward to the clinical advancement of clazakizumab and the potential it has to bring a new treatment to patients suffering with RA.” In a separate pre-clinical study of in-vitro assays, also being presented at the ACR annual meeting, clazakizumab was shown to bind to the IL-6 cytokine with high affinity and block various IL-6-induced functions more potently than tocilizumab, an RA treatment currently on the market that targets the IL-6 pathway. About the Phase IIb Study This was a randomized, dose-ranging, Phase IIb study which evaluated the efficacy and safety of clazakizumab subcutaneous injection alone or in combination with methotrexate (MTX). The study included 418 adults with moderate-to-severe active rheumatoid arthritis (RA) who experienced an inadequate response to MTX. Participants were enrolled and treated in 115 sites throughout North and South America, Europe and Asia. Participants were randomized to one of seven treatment arms: once monthly clazakizumab 25mg, 100mg or 200mg, all on MTX background; once monthly clazakizumab 100mg or 200mg without MTX; MTX alone; or twice monthly adalimumab 40mg + MTX. At week 12, ACR20 response rates (the primary endpoint) were: 78%, clazakizumab 25mg + MTX (p