Khondrion, a biopharmaceutical company focused on therapies for primary mitochondrial disease (PMD), has received FDA clearance for its Investigational New Drug (IND) application for sonlicromanol. This clearance paves the way for a pivotal Phase 3 clinical trial evaluating the drug's potential in adult patients with PMD caused by the m.3243A>G mutation, the most prevalent genetic defect associated with the condition.
The Phase 3 trial, slated to begin in 2025, is a 52-week, double-blind, randomized, placebo-controlled, multi-center study. It aims to enroll 150 adult patients with genetically confirmed m.3243A>G mitochondrial DNA variant. The primary endpoints will focus on chronic fatigue, measured by the Neuro-QoL Fatigue short form questionnaire, and muscle weakness, assessed using the Five Times Sit-to-Stand test. These endpoints were selected based on their relevance to the most burdensome and frequently occurring effects of the disease, as reported by patients.
Sonlicromanol: A Novel Approach to PMD Treatment
Sonlicromanol is a first-in-class, brain-penetrant redox-modulator with anti-inflammatory properties. It is designed to target key metabolic and inflammatory pathways implicated in PMD. Preclinical and clinical data suggest that sonlicromanol may have disease-modifying potential.
Previous clinical trials, including a Phase 2b program published in Brain, have demonstrated encouraging results. The 52-week extension study showed durable improvements in chronic fatigue and muscle weakness among patients treated with sonlicromanol. Specifically, the open-label extension of the Phase 2b program showed statistically significant improvements in the Neuro-QoL Fatigue (p=0.004) and Five Times Sit-to-Stand test (p=0.0161).
Addressing an Unmet Need in PMD
PMDs are a group of inherited neurometabolic disorders affecting approximately 1 in 4,300 individuals in the US. The m.3243A>G variant is the most common genetic defect, with an estimated prevalence of 4.4:100,000. Currently, there are no approved therapies specifically targeting PMD associated with this variant.
"The FDA’s clearance of our IND application for a pivotal Phase 3 trial marks another important milestone for Khondrion’s development of sonlicromanol, a disease-modifying therapy for primary mitochondrial disease that is so desperately needed by PMD patients," said Prof. Dr. Jan Smeitink, Chief Executive Officer at Khondrion. "We look forward to sharing progress of our clinical program including its expected initiation next year."
Sonlicromanol has already been investigated in multiple clinical trials, including studies in adult PMD patients with the m.3243A>G mutation and a Phase 2 study in children with genetically confirmed PMD suffering from motor symptoms. Data from these trials have indicated a favorable safety profile, with some patients receiving sonlicromanol for over two and a half years under a named patient program.
