Idorsia Drug Flops in Fabry Disease, Program's Future Pending


Biotech firm Idorsia today reports that the trial of its candidate treatment for Fabry disease has failed to meet its primary endpoint, leaving the illness with a still large unmet need for oral therapies. 

Its Phase III MODIFY study had hoped to find a positive effect of its oral substrate reduction therapy lucerastat on adult patients who have been diagnosed with Fabry disease. Fabry disease is a rare, genetic illness that leads to nervous system damage, characterized by neuropathic pain and damage to the cardiovascular and gastrointestinal systems. It also damages major organs such as the skin, ears, eyes, lungs, and kidneys. 

Patients diagnosed with this disease will have a much lower or absent a-galactosidase (alpha-GaIA), which is an enzyme that breaks down globotriaosylceramide (Gb3), which, when accumulated, resulting in a reduced life expectancy and poor quality of life. 

At present, there are hardly any well-tolerated oral treatments that address these symptoms. Fabry disease patients are typically given agalsidase-beta (Fabrazyme by Sanofi Genzyme), agalsidase-alpha (Replagal by Shire, now Takeda), or migalastat hydrochloride (Galafod by Amicus Therapeutics) to help assist the delivery of blood supply to the brain and normalize organ function. All three are FDA-approved. Other drugs are only intended to provide relief for individual symptoms.

The MODIFY trial evaluated the effect of oral monotherapy candidate lucerastat in 118 patients over a period of six months, with a 2:1 ratio of receiving either lucerastat or a placebo. At the end of the study, which produced the outcome reported with no reduction in neuropathic pain, 107 of the participants opted to join an extended clinical trial (labeled NCT03737214) by another 48 months to determine the tolerability and long-term safety of the drug, as well as its efficacy on both heart and kidney function.

"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," said Jean-Peal Clozel, managing director and chief executive officer of Idorsia, in a statement. 

It has been quite a busy year for Idorsia, which posted positive first half financial results in July on the back of a strong clinical development pipeline. Idorsia is currently working on several trials to find treatments for insomnia, hypertension, systemic lupus erythematosus, rare lysosomal storage disorders, cerebral vasospasm, binge eating disorders, pediatric epilepsy, and several others involving immune response. 

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