Promising Crohn disease data presented at ECCO for the IL-23 mAb, MEDI2070/AMG-139

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• A number of ECCO presenters commented on the promise of Stelara as a candidate treatment of Crohn disease (and even ulcerative colitis as well).  Phase 3 data are expected in approx 1yr
• Stelara (approved for RA and PsA)  targets p40, a common subunit of IL-12 and IL-23
• AstraZeneca and Amgen are co-developing a related mAb, MEDI2070/AMG-139 for Crohn disease  
• In contrast to Stelara, MEDI2070 targets the p19 subunit of IL-23, leaving the IL-12 pathway unimpeded.  This approach is being adopted for other indications such as PsO, with the suggestion that this may reduce the risk of infection.  To date this has been unproven
• Phase 2a Crohn disease data were presented at ECCO (for a copy of slides please contact us)
• 119 Crohn disease patients received 700mg iv MEDI2070 on days 1 and 29
• Clinical response (CDAI reduction of great than 100pt or CDAI less than 150pt) at 8wk was significantly improved vs placebo, even though 90% patients had previously received 1-2 TNFirs
• A composite endpoint combining symptom and biochemical improvement enhanced apparent efficacy
• TEAEs were unremarkable – in particular infection was unaffected

Comments: The challenge faced by AZ/Amgen will be to differentiate MEDI2070 and Stelara if both are approved. This is particularly so given the likely lead time that Janssen will gain.  Differentiation in terms of infection is questionable.  Possibly  more interesting are potential benefits drawn from psoriasis data.  Numerous IL-23 mAbs are being developed in this space and a consistent observation is the durability of response after treatment withdrawal.  This was particularly remarkable for BI 655066 (data reported last year), also in development for IBD.  Explanation of this phenomenon has yet to be offered although some are suggesting a resetting of the immune system.  Demonstration prolonged maintenance in Crohn disease following treatment tapering would be of obvious benefit and may be considered in Phase 3 designs