Idorsia: Failure in Phase III

The Allschwil-based company announced that in its Phase III study MODIFY, lucerastat did not meet its primary endpoint in patients with Fabry disease. The news came as a surprise to the company, as the the drug seemed to be doing just what it was designed to do: “Lucerastat was well tolerated and biochemically it did exactly what we were expecting; as previously seen, in this study we saw a substantial and consistent reduction of plasma Gb3, confirming the pharmacological activity of lucerastat,” said Guy Braunstein, head of Idorsia’s Global Clinical Development. He added: “Despite this biological effect, no reduction in neuropathic pain was observed after six months of treatment.”

Fabry disease is a rare, genetic, lysosomal storage disorder that results in reduced ?-galactosidase A –  an enzyme that normally breaks down a fatty product known as globotriaosylceramide (Gb3) in the cells of the body. Over time, this results in an accumulation of Gb3 deposits throughout the body, leading to progressive symptoms, such as neuropathic pain. Reducing the Gb3 accumulation, however, did not bring with it a pain reduction in the MODIFY study, leaving Idorsia with an uncertain future. “Taking into account the quality of the study, the volume of data we have collected, and some observations made in the six-month double-blind placebo-controlled treatment period, we need to wait for the results of the interim analysis of the open-label phase before making a decision. I expect to be in a position to share our future direction before the end of year,”  commented Idorsia CEO Jean-Paul Clozel.