clazakizumab. BMS-945429, ALD518
Bristol-Myers Squibb, phase 2b study, rheumatoid arthritis,
NONPROPRIETARY NAME ADOPTED BY THE USAN COUNCIL
PRONUNCIATION klaz” a kiz’ ue mab
THERAPEUTIC CLAIM Autoimmune diseases, rheumatoid arthritis
1. Immunoglobulin G1, anti-(human interleukin 6) (human-Oryctolagus cuniculus monoclonal BMS-945429/ALD518 heavy chain), disulfide with human-Oryctolagus cuniculus monoclonal BMS-945429/ALD518 κ-chain, dimer
2. Immunoglobulin G1, anti-(human interleukin-6 (B-cell stimulatory factor 2, CTL differentiation factor, hybridoma growth factor, interferon beta-2)); humanized rabbit monoclonal BMS-945429/ALD518 [300-alanine(CH2-N67>A67)]1 heavy chain (223-217′)-disulfide with humanized rabbit monoclonal BMS-945429/ALD518 light chain dimer (229-229”:232-232”)-bisdisulfide, O-glycosylated
MOLECULAR FORMULA C6426H9972N1724O2032S42
MOLECULAR WEIGHT 145.2 kDa
SPONSOR Bristol-Myers Squibb
CODE DESIGNATION BMS-945429, ALD518
CAS REGISTRY NUMBER 1236278-28-6
Bristol-Myers Squibbalong with Alder Biopharmaceuticals, announced the presentation of efficacy and safety data from a Phase 2b 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, MD, 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 exclusive worldwide rights to develop and commercialize clazakizumab for all indications outside of cancer under a collaboration agreement with its discoverer, Alder Biopharmaceuticals.
immunoglobulin G1-kappa, anti-[Homo sapiens IL6 (interleukin 6, IL-6)], humanized monoclonal antibody;
gamma1 heavy chain (1-450) [humanized VH (Homo sapiens IGHV3-66*01 (83.50%) -(IGHD)-IGHJ3*02 M123>L (115)) [8.8.14] (1-120) -Homo sapiens IGHG1*03 CH