Further data presented at ECCO on MAdCAM mAb, PF-00547659 - efficacy demonstrated in ulcerative colitis

This content is sampled from our coverage of ECCO last week and part of our UpdatesPlus service. UpdatesPlus-IBD is a regular report, and is part of our inflammation and dermatology collection. Reports are accompanied by ad hoc e-mail alerts providing near real time analysis of key breaking events.  For access to our full and in depth ECCO report or further information on UpdatesPlus please contact  jon.goldhill@leaddiscovery.co.uk - or access our UpdatesPlus product brochure

• Pfizer provided an update on PF-00547659, its MAdCAM mAb, during the company’s JP Morgan presentation in Jan 2015.  Specifically, data were presented from the Phase 2b ulcerative colitis study, TURANDOT
  
• Approximately 60% patients were TNFi experienced.  12wk clinical remission rates were as high as 24%, but a loss of response at higher doses was observed possibly reflecting a block of protective T cells
• Further data were reported at ECCO (for full presentation please contact us)
• Particularly interesting was mucosal healing response which reflected the clinical remission response curve
• Despite the bell shaped endoscopic response, calprotectin levels fell at all doses
• MAdCAM levels, a biomarker of PF-00547659 fell at 7.5mg and reached 95% inhibition at 22mg

Comments: The new mucosal healing data presented at ECCO is impressive with a delta of 20% at 12wks (vs 16% at 6wks for Entyvio and 10% at 12wk for Humira in ULTRA 2).  Despite this, the dose response is a concern suggesting that at higher doses of PF-00547659, efficacy may be lost.  This is not such a problem if 22mg is a universally optimal dose however this may not be the case, with maximal effective dose potentially depending on the characteristics of the individual.  Moreover, it is possible that there is a balance between positive and negative impact across the entire dose response with an overall negative effect only becoming evident at high doses.  If this is the case more selective targeting, if possible, could further boost efficacy.  These issues deserve further investigation.  The apparent dissociation of calprotectin and mucosal healing is difficult to explain and also warrants further investigation