Tisento Therapeutics announced that the U.S. Food and Drug Administration has granted Fast Track designation to zagociguat for the treatment of MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes). The designation recognizes the significant unmet medical need for this rare mitochondrial disease and the potential of zagociguat to address both neurological and systemic manifestations.
MELAS is a rare mitochondrial disease affecting multiple organ systems, characterized by severe and burdensome symptoms including chronic fatigue, cognitive dysfunction, muscle weakness, seizures, and stroke-like episodes. The disease often leads to social isolation, reduced quality of life, and shortened life expectancy. Currently, there are no approved treatments for MELAS, with disease management limited to symptomatic treatments and lifestyle changes that are inadequate to manage the debilitating consequences.
Novel Mechanism of Action
Zagociguat represents a first-in-class, brain-penetrant soluble guanylate cyclase (sGC) stimulator. The drug targets sGC, an enzyme found in virtually every cell throughout the body that controls critical physiological functions including neuronal function and blood flow. By stimulating this enzyme, zagociguat is hypothesized to rebalance dysregulated cellular pathways in MELAS and restore cellular functions that support mitochondria, potentially helping restore mitochondrial energy production and physiological function.
In a Phase 2a study in patients with MELAS, zagociguat demonstrated a favorable safety profile with exposure throughout the body including the central nervous system. The study showed improvements in neuronal function, mitochondrial function, and blood flow in the brain.
Phase 2b PRIZM Study
The global Phase 2b PRIZM study is currently evaluating zagociguat's impact on fatigue, cognitive impairment, and other key aspects of MELAS. The randomized, placebo-controlled trial is investigating oral zagociguat at doses of 15 mg or 30 mg compared to placebo, administered once-daily for 12 weeks in participants with genetically and phenotypically defined MELAS.
The study features a crossover design with two 12-week treatment periods separated by a 4-week washout period. All participants will receive zagociguat during one treatment period and placebo during the other. Those completing the study may be eligible for an open-label extension study.
PRIZM will enroll approximately 44 participants at mitochondrial disease centers of excellence across the U.S., Italy, Germany, United Kingdom, Australia, and Canada. The clinical outcome assessments and endpoint strategy were informed by Tisento's interview study in which individuals living with MELAS described the symptoms and impacts most important to them.
Company Leadership Perspective
"People living with MELAS and their families face tremendous challenges and deserve to have treatments that address the aspects of the disease that matter most to them," said Peter Hecht, PhD, chief executive officer of Tisento. "We are pleased to receive Fast Track designation from the FDA in recognition of the MELAS community's unmet medical needs and the potential of zagociguat to be a meaningful therapeutic option to address both neurological and systemic manifestations of the disease."
The Fast Track designation is designed to facilitate development and potentially expedite review of medicines treating serious conditions with unmet medical needs, with the goal of getting important new drugs to patients earlier.
Tisento Therapeutics is a privately held biotech company developing novel medicines for diseases with significant unmet need, beginning with MELAS and other genetic mitochondrial diseases. The company's approach centers on listening to patients and channeling insights into research and clinical programs.
