First Patient Dosed in Phase 3 KHENERFIN Study of Sonlicromanol for m.3243A>G Primary Mitochondrial Disease
Khondrion has announced a major milestone in the development of potential treatments for primary mitochondrial diseases: the first patient has now been dosed in the pivotal Phase 3 KHENERFIN study evaluating sonlicromanol, the company’s investigational therapy for adults with the m.3243A>G mutation. This genetic variant is the most common cause of primary mitochondrial disease and is associated with progressive, multisystem involvement and significant unmet medical need.
The 52‑week, randomized, placebo‑controlled trial will assess the efficacy and safety of sonlicromanol, a novel brain‑penetrant redox‑modulator with anti‑ferroptotic and anti‑inflammatory properties. The study’s design builds on encouraging signals from Khondrion’s Phase 2b programme, with primary endpoints focused on the symptoms patients report as most debilitating: chronic fatigue and muscle weakness.
Jasper Levink, CEO of Khondrion, highlighted the importance of this step, noting that the initiation of dosing marks “an important milestone in the development of a potential treatment for patients with m.3243A>G primary mitochondrial disease.” He emphasised that the trial is structured to rigorously evaluate sonlicromanol’s impact on meaningful, patient‑centred outcomes.
Dr. Mirian Jansen, head of the clinical metabolic department at Radboudumc and principal investigator for the study, underscored the burden of m.3243A>G disease, describing it as “a progressive and debilitating condition” that affects multiple organ systems and often leads to increasing disability. She stressed the commitment of investigators to collecting high‑quality data on outcomes that matter in daily life, particularly fatigue and functional decline.
From the patient community, Paula Morandi, Chair of International Mito Patients (IMP), welcomed the news. “Fatigue and muscle weakness are often debilitating and impact every area of life,” she said. “The initiation of the Phase 3 KHENERFIN study is a significant achievement and provides hope to the international mitochondrial disease community.”
The trial aims to enrol up to 220 adults across Europe, the UK, and the US. Participants will be randomized 1:1 to receive either 90 mg sonlicromanol or placebo twice daily for 52 weeks. The two independent primary endpoints are change in NeuroQoL Fatigue Short Form score and performance on the 5‑times sit‑to‑stand test—both key indicators of disease burden and daily functioning.
The launch of KHENERFIN represents an important step forward in the search for effective treatments for mitochondrial disease, and the global patient community will be watching its progress closely.
Paula goes on to say “As IMP, which represents 25 mitochondrial disease patient advocacy groups across five continents, we are encouraged by the progress being made in research and drug development for those living with Primary Mitochondrial Diseases. We optimistically await the outcome of the trial.”