Tuesday, July 2, 2013

Sarilumab at the EULAR 2013 Meeting

I had been wondering, if there is some news on sarilumb as there hadn’t been too much at the ACR 2012 Meeting; see link below.

L.-H. Wang and colleagues presented [FRI0020]: “Preclinical development of sarilumab, the first fully human monoclonal antibody (MAB) against IL-6R alpha: utilization and value of double humanized animal model.” Conclusions: “These results show that sarilumab was biologically active in a humanized mouse model of acute inflammation and achieved a dose‑dependent reduction in SAA following turpentine injection, …”
??? I’m a bit confused and disappointed. I thought we were already past the animal studies.

M. C. Genovese and colleagues presented a post hoc analysis of the MOBILITY study [SAT0117]: “Sarilumab, a subcutaneously-administered, fully-human monoclonal antibody inhibitor of the IL-6 receptor: relationship between EULAR responses and change from baseline of selected clinical parameters.” Conclusions: “Sarilumab doses studied in Phase 3 resulted in a significantly higher proportion of RA patients with improved Hb, hsCRP and EULAR good responses compared to placebo. This preliminary evaluation of a subset of PROs in MOBILITY Part A shows improvements in FACIT and sleep VAS scores that correlated with achievement of a EULAR good response.”
It’s like eight months ago. We only get some preliminary results from a phase 3 study.

R. Fleischmann and colleagues also presented a piece of cake from the MOBILITY study [SAT0136]: “Sarilumab, a fully human MAB against IL-6R alpha, subcutaneously-administered shows significant improvement in RA patients as early as 2 weeks: a time to event analysis for ACR50 and EULAR good response.” Conclusions: “The effect of SAR in reducing signs and symptoms by the ACR50 response and EULAR good and good+moderate criteria was seen early. Pts treated with 150 or 200mg q2w or 100 or 150mg qw were >2 times as likely as Pbo to achieve ACR50 response after 12 wks. A significant improvement in the proportion of EULAR responders was also observed for 4 SAR groups starting at wk 2. These proportional hazard methods support Phase 3 study of 150 and 200mg q2w regimens that provide high hurdle ACR and EULAR clinical responses.”
It doesn’t exceed very much the data, which has been published at the 2012 EULAR Meeting.

And finally let’s look at the study by A. Rafique and colleagues [AB0037]: “Evaluation of the binding kinetics and functional bioassay activity of sarilumab and tocilizumab to the human IL-6 receptor (IL-6R) alpha.” Conclusions: “Based on these in vitro assay data, sarilumab has both a higher relative binding affinity for IL-6Rα, blocks IL-6Rα activation, and inhibits IL-6-induced cellular responses such as cell proliferation at lower concentrations than tocilizumab.”
So, sarilumab might have an edge against tocilizumab.

It might well be that sarilumab would work in lower concentrations, but as tocilizumab has already been evaluated for subcutaneous injection, how big could be an advantage? We've seen two studies, which would be expected before going into phase 2 and 3, and two tidbids from a phase 3 study, which hasn’t been fully evaluated. What are these facts telling us? There must be a strategy included – and I’m not too sure about sarilumab’s future.

ACR 2012: http://rheumatologe.blogspot.de/2012/12/sarilumab-at-acr-2012-in-washington.html  
EULAR 2012: http://rheumatologe.blogspot.de/2012/06/sarilumab-news-from-eular-2012.html  

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