Promising PKC data on AGI's IBS-D drug

Dublin, Ireland-based AGI Therapeutics has reported encouraging findings on the pharmacokinetic profile of its drug candidate Rezular (AGI-003), which is in Phase III clinical trials for the treatment of diarrhoea-predominant irritable bowel syndrome.

AGI noted that Rezular contains arverapamil, the purified R-isomer form of currently-marketed drug verapamil, which contains equal amounts of both the R- and S-isomer that is most potent on cardiac and vascular tissue. In the assessment, there were no detectable levels of the S-isomer following administration under fasting conditions and thus no evidence of any inter-conversion of Rezular to the S-isomer in vivo. Administration of the drug under fed conditions resulted in some increase in area under the plasma concentration curve (AUC) of the R-isomer compared to fasting conditions, while the S-isomer was only detected in the plasma at trace levels matching the amounts known to be present in the purified form of Rezular. These data indicate that the gastrointestinally-active R-isomer, arverapamil, contained in Rezular can be administered to humans without exposing them to clinically relevant levels of the S-isomer, AGI stated.

Under both fed and fasting conditions, both the peak plasma concentration and AUC of the R-isomer after Rezular administration were less than those seen after administration of racemic verapamil. This indicates that patients taking clinically-relevant doses of Rezular will be exposed to lower systemic levels of the R-isomer compared to currently-approved forms of racemic verapamil, the firm noted, adding that this further supports the development approach agreed with the US Food and Drug Administration for Rezular.