Khondrion Doses First Patient in Phase 3 KHENERFIN Study

NIJMEGEN, The Netherlands, April 16, 2026

Khondrion has announced a significant clinical milestone with the first patient dosed in its pivotal Phase 3 KHENERFIN trial evaluating sonlicromanol, an investigational therapy for m.3243A>G-related Primary Mitochondrial Disease. This randomized, placebo-controlled global study (NCT06451757) marks a crucial step forward in addressing one of the most common genetic causes of mitochondrial disease, a condition characterized by progressive, multi-system dysfunction and significant unmet medical need. The advancement into Phase 3 underscores growing confidence in sonlicromanol’s potential, supported by encouraging Phase 2b clinical signals demonstrating improvements in key disease symptoms such as chronic fatigue and muscle weakness.

Phase 3 KHENERFIN Trial Targets Core Disease Burden

The KHENERFIN study is designed to enroll up to 220 adult patients across Europe, the United Kingdom, and the United States, all with genetically confirmed m.3243A>G mitochondrial DNA mutation. Participants will be randomized in a 1:1 ratio to receive either sonlicromanol or placebo over a 52-week treatment period, administered as oral dispersible tablets twice daily.

The trial’s primary endpoints focus on clinically meaningful outcomes, including changes in NeuroQoL Fatigue scores and performance in the 5-times sit-to-stand test, both reflecting the most debilitating aspects of the disease. These endpoints are strategically chosen to evaluate whether the therapy can deliver tangible improvements in patient function, mobility, and quality of life, addressing the daily challenges faced by individuals living with mitochondrial disorders.

Innovative Mechanism Positions Sonlicromanol as Promising Therapy

Sonlicromanol is a novel brain-penetrant redox modulator with anti-ferroptotic and anti-inflammatory properties, designed to target underlying disease mechanisms rather than just symptoms. By addressing oxidative stress and cellular dysfunction, the therapy aims to provide a disease-modifying approach in mitochondrial disorders, where current treatment options remain extremely limited.

Earlier clinical data from the Phase 2b program demonstrated consistent signals of efficacy and a favorable safety profile, supporting its progression into late-stage development. Experts emphasize that fatigue and muscle weakness, the primary endpoints of the study, are among the most burdensome symptoms affecting patients, significantly impacting daily functioning, independence, and overall quality of life.

Global Collaboration and Unmet Need Drive Development

Primary mitochondrial disease caused by the m.3243A>G mutation is a progressive and debilitating condition affecting multiple organ systems, often leading to increasing disability over time. With no approved curative therapies currently available, the KHENERFIN trial represents a critical advancement in rare disease research and drug development.

The study is supported by collaboration with leading clinical centers and patient advocacy groups, reflecting a strong commitment to patient-centered outcomes and high-quality data generation. Industry leaders and patient organizations have highlighted the importance of this milestone, noting that the initiation of Phase 3 dosing provides renewed hope for patients and families affected by mitochondrial diseases worldwide.

As Khondrion advances this pivotal trial, the results are expected to play a decisive role in determining the future of sonlicromanol as a potential first-in-class therapy for mitochondrial disease. With its innovative mechanism, strong clinical foundation, and focus on meaningful patient outcomes, the KHENERFIN study represents a major step toward addressing a critical gap in rare disease treatment and improving the lives of patients facing severe and life-altering conditions.

Source: Khondrion press release