UpdatesPlus Alert: GSK announces positive topline data from Phase 3 sirukumab program

Source:  UpdatesPlus-Rheumatoid Arthritis - for a full and in depth analysis of all key developments in rheumatoid arthritis R&D contact jon.goldhill@leaddiscovery.co.uk

• Sirukumab is a human anti-IL-6 mAb being developed by J&J and GSK.  This is differentiated from (Ro)Actemra and more recently sarilumab which target the IL-6 receptor
  
• A 2 part Phase 2 MTX-IR study of sirukumab opened in 2008.  Part A evaluated q2w sirukumab (100mg sc).  Part B subsequently evaluated q2w (100mg) or q4w dosing (25, 50 or 100mg)
• Data presented at ACR 2011 reported high efficacy (see below) with 100mg q2w producing an ACR50 response of 27% vs 3% with placebo.  Continued treatment with sirukumab increased ACR50 rates further to 60% by 24wks (note that placebo treated patients switched to sirukumab at 12wks preventing placebo correction; the uncorrected rates in corresponding (Ro)Actemra studies were however 30-45%).  It has previously been commented that the high efficacy of sirukumab may reflect the lower expression of ligand vs receptor and/or the high affinity of sirukumab
• Sirukumab entered Phase 3 in 2012.  The program comprises a DMARD-IR and TNFi-IR study (see below).  A head to head comparison with Humira has also been conducted.  Although the
  DMARD-IR study is showing on clinicaltrials.gov as reaching its primary endpoint time frame in 2016, the study stopped enrolling in Oct 2014 with primary endpoints at 16wk for ACR 20 and 52wk for radiographic progression
• GSK has today announced that it has received positive top-line results from the Phase 3 program.  There were reportedly no unexpected safety findings and filing is anticipated for 2016

Comments:  We note that GSK did not specify in its press release that positive data had been received from all of the Phase 3 studies; simply the Phase 3 program.  We have no reason to suspect that any of the three pivotal studies produced negative data although it is possible that 52wk radiographic data have yet to be analyzed from SIRROUND-D.  Also of note, GSK failed to give any any idea of efficacy.  Further data may not become available until EULAR (June 2016) by which time we expect filing to have taken place