BMS-986231 (Bristol-Myers Squibb/Ligand) is a second-generation prodrug that chemically breaks down to produce nitroxyl (HNO) and an inactive byproduct. HNO is thought to have a dual mode of action, by improving cardiac function and acting as a vasodilator. Additionally, HNO is thought to enhance myocardial function by improving calcium cycling and also myofilament calcium sensitivity. Finally, HNO acts a vasodilator through activation of soluble guanylate cyclase and activation of potassium channels in vascular smooth muscle.
BMS-986231’s proposed dual mode of action and good tolerability could be presented as an improvement over currently used phosphodiesterase III inhibitors and Simdax (levosimendan; Orion/Tenax Therapeutics). However, more clinical data are required in order to verify the mechanism and identify any possible safety issues. The potential to act as an inotropic agent and a potent vasodilator could result in significant uptake in a highly genericized acute decompensated heart failure market, but until more is known regarding safety, no clear conclusions can be made regarding this product.
- BMS-986231: Acute decompensated heart failure (ADHF)
Figure 1: BMS-986231 for ADHF - SWOT analysis
Figure 2: The author’s drug assessment summary of BMS-986231 for ADHF
Figure 3: The author’s drug assessment summary of BMS-986231 for ADHF
List of Tables
Table 1: BMS-986231 drug profile
Table 2: BMS-986231 Phase II data in ADHF
Table 3: BMS-986231 Phase II trials in ADHF