Sirukumab at the EULAR 2012

Sirukumab (formerly known as CNTO 136) is a human MAB that binds to the cytokine IL-6, designed for the treatment of rheumatoid arthritis. So sirukumab will be competiting with tocilizumab. Several studies have been presented at the 2012 EULAR meeting in Berlin. Actually there have been three abstracts to one study and another study using serum samples of the mentioned phase 2 study.


B. Hsu and colleagues presented a phase 2 study with proof of concept part and a dose ranging part to determine efficacious and safe sirukumab dose regimens. It doesn´t surprise that "sirukumab in combination with MTX, improved physical function as well as reduced multiple other signs and symptoms of RA." As tocilizumab marketing is stressing the point of monotherapy, this study on sirukumab comes in combination with methotrexate.


[FRI0181] SIRUKUMAB, A HUMAN ANTI-IL-6 MONOCLONAL ANTIBODY, IMPROVES PHYSICAL FUNCTION IN PATIENTS WITH ACTIVE RA DESPITE METHOTREXATE THERAPY: RESULTS FROM A 2-PART, PROOF-OF-CONCEPT, DOSE-RANGING, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 2 STUDY
B. Hsu1, C.-F. Chiou1, S. Sheng1, J. Smolen2, M. Weinblatt3. 1Janssen R&D, Spring House, PA, United States; 2Medical U of Vienna and Hietzing Hospital, Vienna, Austria; 3Brigham & Women's Hosp, Boston, MA, United States
Conclusions: In this Phase 2 study of patients with active RA despite MTX therapy, sirukumab in combination with MTX, improved physical function as well as reduced multiple other signs and symptoms of RA.


B. Hsu and colleagues show further details of the phase 2 study in another abstract. The new provisional 2011 ACR/EULAR rheumatoid arthritis (RA) remission criteria were used to assess remission rates. The highest remission rates were achieved in the 100 mgs sirukumab SC group.


[OP0025] RESULTS FROM A MULTICENTER, INTERNATIONAL, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 2 STUDY OF SIRUKUMAB, A HUMAN ANTI-IL-6 MONOCLONAL ANTIBODY, IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS DESPITE METHOTREXATE THERAPY
B. Hsu1, S. Sheng1, M.E. Weinblatt2, J.S. Smolen3. 1Janssen Research & Development, LLC, Spring House, PA; 2Brigham and Women's Hospital, Boston, MA, United States; 3Medical University of Vienna and Hietzing Hospital, Vienna, Austria
Conclusions: Higher remission rates according to both the 2011 ACR/EULAR and the DAS28 (CRP) criteria were achieved with sirukumab at SC dose regimens ranging from 25-100 mg q2w-q4w compared with placebo. After placebo crossover to sirukumab, all groups achieved increasing remission rates over time with continued sirukumab treatment. The highest sirukumab dose regimen (100 mg q2w) achieved the highest remission rates. The 2011 ACR/EULAR criteria were more stringent than the DAS28 (CRP) criteria; and the Boolean-based definition was more stringent than the SDAI-based definition.


It feels like Hollywood comes to EULAR - here´s part three of the story. B. Hsu and colleagues on efficacy and safety of SC sirukumab. " Thru wk38, AEs occurred more often w/ SRM than PBO (81 vs 67%), including minor infections/infestations (31 vs 13%), GI disorders (19 vs 10%), & injection site reactions (16 vs 3%). Leukopenia (19, 13% [1 NCI Gr 3]), neutropenia (5, 3% [3 Gr 3]), thrombocytopenia (3, 2% [1 Gr 3, 1 Gr 4]), & lymphopenia (2, 1%, [1 Gr 3, 1 Gr 4]) were reported w/ SRM." We have to see later in real life as for leukopenia and neutropenia. See my blog for these in patients treted with tocilizumab: LINK " SRM was efficacious & generally well tolerated." Look for the whole conclusion below:


[THU0100] RESULTS FROM A 2-PART, PROOF-OF-CONCEPT, DOSE-RANGING, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 2 STUDY OF SIRUKUMAB, A HUMAN ANTI-IL-6 MONOCLONAL ANTIBODY, IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS DESPITE METHOTREXATE THERAPY
B. Hsu1, S. Sheng1, J.S. Smolen2, M.E. Weinblatt3. 1Janssen R&D, Spring House, PA, United States; 2Med U Vienna & Hietzing Hosp, Vienna, Austria; 3Brigham & Women's Hosp, Boston, MA, United States
Conclusions: SRM was efficacious & generally well tolerated. SRM PK were linear over SC regimens ranging from 25 to 100mg.


G. Toedter and colleagues looked at hepcidin levels and markers of anemia in patients of the phase 2 study on sirukumab. They concluded that sirukumab might be effective in reversing inlammation related anemia, but so do other drugs and tocilizumab.


[THU0105] EFFECT OF SIRUKUMAB ON HEPCIDIN LEVELS AND MARKERS OF ANEMIA: RESULTS OF A PHASE 2B TRIAL IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS DESPITE METHOTREXATE THERAPY
G. Toedter, S. Sague, X. Wu, M. Curran, B. Hsu. Janssen Research & Development, LLC, Spring House, PA, United States
Conclusions: Sirukumab was effective in reducing serum concentrations of hepcidin through week 12 of treatment. Serum hemoglobin levels in anemic patients increased significantly following sirukumab treatment, with half of the patients normalizing hemoglobin levels. This indicates that in addition to demonstrating efficacy, treatment of RA patients with sirukumab may be effective in reversing inflammation-related anemia.


Is there a market for sirukumab. Of course, but it´s largely a me too part of the market, if tocilizumab will be out on the market with SC preparation. Janssen would need to establish a SC sirukumab without the need of methotrexate to compete.