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Khondrion's Sonlicromanol Receives FDA Clearance for Phase 3 Trial in Primary Mitochondrial Disease

• Khondrion's sonlicromanol, a novel redox-modulator, has received FDA clearance for a Phase 3 trial targeting primary mitochondrial disease (PMD) caused by the m.3243A>G mutation. • The 52-week trial will assess sonlicromanol's impact on chronic fatigue and muscle weakness, the most burdensome symptoms of PMD, enrolling 150 adult patients. • Sonlicromanol demonstrated durable improvements in fatigue and muscle weakness in a Phase 2b extension study, supporting its potential as a disease-modifying therapy. • The Phase 3 trial's design includes the Neuro-QoL Fatigue questionnaire and the Five Times Sit-to-Stand test as primary endpoints to evaluate treatment efficacy.

Khondrion, a biopharmaceutical company focused on mitochondrial disease, has announced FDA clearance of its Investigational New Drug (IND) application for sonlicromanol. This clearance paves the way for a pivotal Phase 3 clinical trial evaluating the drug's efficacy in adult patients with primary mitochondrial disease (PMD) due to the m.3243A>G mutation, the most common genetic defect associated with PMD.
The Phase 3 trial is set to commence in 2025 and will be a 52-week, double-blind, randomized, placebo-controlled, multi-center, parallel-group study. It aims to enroll 150 adult patients with genetically confirmed m.3243A>G mitochondrial DNA tRNALeu(UUR) variant. The primary endpoints selected for this study are the Neuro-QoL Fatigue short form questionnaire and the Five Times Sit-to-Stand test, focusing on chronic fatigue and muscle weakness, which are the most debilitating symptoms reported by PMD patients.

Sonlicromanol: A Potential Disease-Modifying Therapy

Sonlicromanol is Khondrion's lead drug candidate, characterized as a potentially disease-modifying, first-in-class, brain-penetrant redox-modulator with anti-inflammatory properties. It is designed to target key metabolic and inflammatory pathways implicated in PMD.
Prior clinical investigations, including a multicenter Phase 2b program published in Brain, have indicated significant patient benefits with sonlicromanol. A 52-week extension study, with some patients treated for up to 78 weeks, demonstrated sustained improvements in chronic fatigue and muscle weakness among patients receiving sonlicromanol.

Clinical Significance and Unmet Need

There are currently no approved therapies for PMD associated with the m.3243A>G variant, which has an estimated prevalence of 4.4 per 100,000. PMDs, as a group, are the most prevalent inherited neurometabolic disorders, affecting at least 1 in 4,300 individuals, translating to approximately 65,000 people in the US alone. The development of sonlicromanol addresses a critical unmet medical need for these patients.

Prior Clinical Experience

Sonlicromanol has been evaluated in four clinical trials, including three 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 a named patient program in the Netherlands, where seven patients received sonlicromanol for over two and a half years following the Phase 2b extension study, supports the drug's favorable safety profile.

Company Leadership Perspective

Prof. Dr. Jan Smeitink, CEO of Khondrion, stated, "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. We look forward to sharing progress of our clinical program including its expected initiation next year."
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Reference News

[1]
Khondrion receives FDA clearance of IND application for - GlobeNewswire
globenewswire.com · Nov 14, 2024

Khondrion receives FDA clearance for a Phase 3 trial of sonlicromanol, a brain-penetrant redox-modulator with anti-infla...

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