Zagociguat, an Investigational Tx for Mitochondrial Diseases, Gets Orphan Drug Status

The Food and Drug Administration (FDA) has granted Orphan Drug designation to zagociguat for the treatment of mitochondrial disease.

Zagociguat is a small molecule activator of soluble guanylate cyclase (sGC) designed to increase nitric oxide (NO) signaling resulting in an increase in cyclic guanosine monophosphate (cGMP) production. It is believed that zagociguat could potentially improve cognition and function in patients with serious diseases, including mitochondrial disease, by compensating for deficient NO-sGC-cGMP signaling.

The designation is supported by data from an open-label, phase 2a study (ClinicalTrials.gov Identifier: NCT04475549) that evaluated the safety and tolerability of zagociguat in adults with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). Treatment with zagociguat was found to improve multiple disease-relevant biomarkers, including mitochondrial function, inflammation, cerebral blood flow, functional brain connectivity, and visually evoked brain activation.

“Orphan Drug designation underscores the FDA’s recognition of zagociguat’s potential promise as a first-ever therapy for patients with MELAS, a rare, genetic mitochondrial disease,” said Peter Hecht, PhD, CEO of Cyclerion. “Cyclerion is working expeditiously to advance this potential treatment to help address the immense unmet needs of patients with MELAS, a patient population in desperate need of therapies.”