Clazakizumab at the EULAR 2014 Meeting in Paris

Clazakizumab is an anti-IL-6 MAB. I haven't written much on clazakizumab so far. Last year at the ACR 2013 Meeting in San Diego there had been a poster/abstract on clazakizumab, on which clazakizumab showed a higher potency than tocilizumab [#2385]. But will this be an advantage? Tocilizumab SC is already available and is still might take a while until clazakizumab comes to the market.

S. Du and colleagues presented the following study [SAT0210]: "X-RAY AND MRI RESULTS FROM A PHASE IIB STUDY OF

SUBCUTANEOUS ANTI-INTERLEUKIN-6 MONOCLONAL ANTIBODY CLAZAKIZUMAB WITH OR WITHOUT MTX IN ADULTS WITH MODERATE-TO-SEVERE ACTIVE RA AND INADEQUATE RESPONSE TO CONVENTIONAL DMARDS INCLUDING METHOTREXATE". Conclusions: Clazakizumab in combination with MTX demonstrated reduced progression of joint damage by MRI as early as 12 weeks and by X-ray after 24 weeks. Larger trials with clazakizumab in RA are warranted to confirm these findings." But good as preliminary data!

M. Weinblatt and colleagues presented [SAT0244]: "A PHASE IIB STUDY OF THE EFFICACY AND SAFETY OF SUBCUTANEOUS CLAZAKIZUMAB (ANTI-IL-6 MONOCLONAL ANTIBODY) WITH OR WITHOUT METHOTREXATE IN ADULTS WITH MODERATE-TO-SEVERE ACTIVE RHEUMATOID ARTHRITIS AND AN INADEQUATE RESPONSE TO METHOTREXATE". N=418 patients were randomized! In results we find: " The rates of serious adverse events ranged from 8.3 to 13.3% in CLZ arms versus 3.3% for pbo ...". Conclusions: "Clazakizumab as monotherapy or in combination with MTX demonstrated efficacy in controlling the signs and symptoms of RA. At Week 24, remission rates with clazakizumab + MTX trended higher than with ADA + MTX. Its safety profile was consistent with the known pharmacology of IL-6 blockade. Clazakizumab is a promising future treatment for RA that warrants further investigation." Still too early to call us off safety concerns!

E. Alemao and colleagues presented [AB0423] "IMPACT OF ANTI-IL-6 MONOCLONAL ANTIBODY, CLAZAKIZUMAB, ON PATIENT-REPORTED OUTCOMES IN PATIENTS WITH RHEUMATOID ARTHRITIS AND AN INADEQUATE RESPONSE TO METHOTREXATE IN A PHASE IIB STUDY".

Conclusions: Treatment with clazakizumab with or without MTX resulted in improvements in multiple PROs and a greater proportion of patients achieved MCID (minimal clinically important differences) on these PROs (patient-reported outcomes) compared with MTX alone in patients with RA with an inadequate response to MTX."

Promising drug candidate, but still has to present phase 3 studies. I hope there won't be new safety concerns as I'm already alerted by the 8.3% to 13.3% serious adverse events in the clazakizumab arms versus 3.3% for placebo [SAT0244]; the authors of the study call the safety profile consistent with the known pharmacology of IL-6 blockade, however. Maybe, we'll get a new drug, but as there already exists an approved anti-IL-6 MAB, where's the niche for this one? Hopefully the company answers this question before coming to the market.