Letter to the editor regarding conflicting reports of opaganib efficacy against high-fat diet-induced obesity.

Opaganib is a first-in-class, clinical stage drug that modulates sphingolipid metabolism resulting in anticancer and anti-inflammatory activity in vivo in many rodent models. Of particular relevance, we previously showed that opaganib has anti-obesity efficacy in mice fed a high fat diet. A recent publication by another group reported that opaganib has no beneficial activity in the same model. We argue herein that those studies were flawed because of the use of an unusually low opaganib dose, as well as a route and schedule of administration that do not provide sufficient blood levels for opaganib efficacy. We are concerned that these limitations provide a misleading representation of opaganib efficacy in this model of obesity and type 2 diabetes.