Many companies are attempting to reduce the GI bleeding, ulcers and perforations caused by administration of NSAIDS (e.g., ibuprofen, naproxen, aspirin). Since Vioxx was removed from the market (and it was a safer NSAID with respect to GI), there has been an surge of NSAID activity around these existing actives. We understand that the FDA’s DAARP division is the busiest. We know from many pre-IND and IND meetings that they are probably the most conservative.
Companies are modifying formulations by coating tablets or beads or even moving from oral to topical administration. Others are developing pro-drugs with different targets.
PLx Pharma has examined the mechanism of the GI-attack by NSAIDs and believes that NSAIDs bind to mucosal phosphatidylcholine (PC, a surfactant), which allows acid to permeate and induce necrosis, which is clinically manifested as bleeding, ulcers and perforations. PLx created the pro-drug NSAID-PC, pre-binding the phosphatidylcholine to the NSAID. The NSAID-PC then uncouples post-stomach. After uncoupling, the NSAID behaves just like the RLD and is regulated by FDA accordingly. That is, DAARP understands that there is some circulation of the NSAIDs that can still cause GI problems.
We’ll examine NSAID issues over the next few weeks. Stay tuned.