Sunday, October 11, 2015

BI 655066 alert - Phase 3 psoriasis studies announced as Boehringer reports further impressive Phase 2 data for its IL-23 mAb

This exert is from our live coverage of EADV - for comprehensive coverage contact
  • Boehringer presented Phase 2 proof of concept data for IL-23 mAb, BI 655066 at EADV 2014
  • BI 655066 targets the p19 subunit of the IL-23 receptor, while Stelara targets the p40 subunit which is shared by the IL-12 and IL-23 receptor
  • A  single dose produced 58% PASI90 across doses.  Durability of response was remarkable with PASI100 at 12wks maintained to 41-66wks
  • A Phase 2 dose ranging study reported at AAD confirmed efficacy
  • At 90mg or 180mg (0, 4 and 16wks) BI 655066 produced  PASI90 rates of 66% and 86% at 24wks
  • New data from the follow up period were reported this week at EADV (see below)
  • PASI90 rates remained very high at 20 wks after the last treatment with 90mg or 180mg (ie at 36wks).  Rates were 69% and 81% respectively vs 30% for Stelara which started to drop off rapidly from 8wks after the last dose
  • The time to reach PASI90 was presented and this was twice as fast with BI 655066 (57d).  Of interest, the speed of response was related to dose
  • For those patients who achieved PASI 90 a KM curve analysis reported a dramatic increase in the time to PASI90 loss.  This was 169d with Stelara; for 180mg BI 655066, 60% of patients still had PASI90 at the end of follow up (169d after the final dose) and hence a value could not be calculated

Comments:  The data continue to be very impressive for BI 655066, with most opinion leaders at EADV expressing considerable excitement around the molecule.  The consensus opinion appears to be that the high level of efficacy is due to the mode of action rather than long half life or other physio-chemical attributes of BI 655066.  This is interesting because the thinking to date has been that Stelara targets both IL-23 and IL-12 and that the latter is a bystander.  The present data suggests that IL-12 may exert some degree of beneficial effect, and hence the net benefit of blocking IL-23 and IL-12 is less than selectively targeting IL-23 alone.  Alternatively the p19 subunit of IL-23 which is targeted by BI 655066 is a component of another receptor which does not include p40, and hence untouched by Stelara.  A further possibility is that for some unknown reason BI 655066 is able to deplete target cells, whereas Stelara cannot. This is all conjecture and the key points remains that the high efficacy continues to be shown and the progress to Phase 3 which we will describe in our next alert

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