Wednesday, June 18, 2014

UpdatesPlus - EULAR 2014- Further data presented on atacicept from APRIL-SLE

The alert below is from our EULAR 2014 coverage.  We have captured most of the key oral and poster presentations delivered at EULAR and will be analyzing these more comprehensively in upcoming issues of our UpdatesPlus service.UpdatesPlus is a service comprising alerts and monthly reports including pipeline and trial updates plus analysis of key information.  The service is designed for industry and academics across the Immunology & Inflammation spectrum.  To register for UpdatesPlus or to get further information please contact

  • Merck Serono's atacicept is an Fc-TACI  fusion protein that neutralizes BAFF and APRIL
  • A  lupus nephritis study closed early due to reported cases of severe infection.  A second SLE study evaluating 75mg or 150mg atacicept (APRIL-SLE) continued at the lower dose and was presented at EULAR and ACR in 2013.  This study employed a loading dose regimen (qw over 4wks followed by q2w dosing for the remaining 48wks)
  • Patients entered a screening period with at least one BILAG A/B score and were treated for flare with steroid.  Steroid dose was then tapered down over approx 10wks and patients who had improved to at least BILAG C/D were randomized to atacicept or control
  • The primary end-point, (BILAG A/B flare over 52wks) was not met at 75mg (58% vs 54% in placebo arm); however patients receiving 150mg demonstrated a reduction (37%)
  • New data presented at EULAR 2014 reported that flares were most often musculoskeletal and mucocutaneous  (lower left in inset)
  • Data were also reported for SLEDAI flare (upper right) and steroid use (lower right).  SLEDAI flare was clearly reduced at both doses.  The number of patients requiring >20mg/d steroid was reduced by 150mg atacicept but not 75mg.  This was reflected in a reduction in the number of patients requiring an increase in steroid dose from baseline
  • As previously reported, two fatal infections were reported in the 150mg arm prior to its discontinuation

Comments:  Merck has recently announced continued development of atacicept in SLE in the Phase 2b ADDRESS II study.  Differing from APRIL-SLE, the study has SRI as a primary endpoint rather than BILAG flare. This is important as SRI incorporates disease improvement (SELENA-SLEDAI) as well as no worsening (BILAG flare).  It is unclear what safeguards are in place to mitigate risk of fatal infection reported in earlier studies. We note that ADDRESS II does not have a loading period and this is likely to have some impact. Likewise reduced exposure from 52 to 24wks may also reduce risk


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