Varespladib

Varespladib blocks secretory phospholipase-A2 (sPLA2), an enzyme fundamental to the functioning of many organisms’ innate immune response. In many animals, including venomous snakes, sPLA2 has evolved into a deadly poison.

As the most enzymatically active of the major classes of snake venom toxins, sPLA2 plays a critical, direct role in life-threatening tissue destruction, bleeding, and paralysis. It is present in 95% of all snake venoms.

Ophirex recognized sPLA2 as an optimal target for treating snakebite envenomation and searched for an effective inhibitor. In Ophirex’s preclinical studies, varespladib demonstrated ideal anti-snake venom properties, and previous clinical studies of the drug for other indications provided valuable data.

Eli Lilly originally discovered and developed varespladib, but after clinical studies of the anti-inflammatory sPLA2 inhibitor in severe sepsis and rheumatoid arthritis did not show efficacy, the company discontinued its program. The data generated included more than 4,000 patients and established varespladib’s excellent safety profile, particularly in acute use.

All venom sPLA2 toxins have the same groove in the "active" part of the venom, which is critical for the venom to work and has not changed over millions of years. Varespladib fits into this universal groove like a wedge, disabling the venom sPLA2 — no matter what type it is or what it looks like on the outside.

In animal models challenged with snake venoms from across the globe, varespladib has shown unparalleled efficacy, rescuing animals from 100% (or more) lethal doses of venoms. In our large animal (porcine) studies, we saw varespladib repeatedly reverse venom-induced paralysis, restore blood clotting, and save lives, outperforming gold-standard antivenoms.