Khondrion Publishes Phase 2b Study on Sonlicromanol's Potential in Primary Mitochondrial Disease

Khondrion, a biopharmaceutical company based in Nijmegen, the Netherlands, has unveiled significant findings from its Phase 2b clinical trials of sonlicromanol, a promising treatment for primary mitochondrial disease (PMD). The results have been published in the scientific journal, Brain. Sonlicromanol is Khondrion’s leading drug candidate and is designed to penetrate the brain and act as a redox-modulator with anti-inflammatory properties. It aims to target vital metabolic and inflammatory pathways associated with PMD.

The Phase 2b clinical development program for sonlicromanol involved adults suffering from the m.3243A>G genetic mutation, which is the most prevalent cause of PMD. This study was a 28-day, randomized, placebo-controlled, three-way cross-over, dose-finding trial with 27 participants. This was followed by a 52-week open-label extension study. The primary focus was on the most challenging symptoms faced by PMD patients, such as muscle weakness, chronic fatigue, pain, and cognitive decline.

The publication highlights the substantial benefits patients experienced from sonlicromanol. Improvements were noted in several areas, including overall health, quality of life, mood, fatigue, pain, and balance control. Patients who had severe symptoms at the start of the study showed more significant improvements, and continued treatment led to further benefits. These positive effects were observed in multiple domains often affected by PMD, indicating that the treatment’s impact was systemic. Consistent with previous trials, sonlicromanol displayed excellent pharmacokinetics and a strong safety profile, being well tolerated over the 52-week period.

Professor Dr. Jan Smeitink, CEO at Khondrion, emphasized the importance of these findings, stating that the data provide robust evidence of sonlicromanol’s potential to benefit PMD patients, who currently lack effective treatment options. He noted that this is the first clinical trial to show a clear reversal of the major symptoms in progressive mitochondrial disease.

Despite the challenges posed by mitochondrial diseases in clinical development, the trial has significantly expanded understanding of sonlicromanol’s long-term safety and efficacy. The Phase 2b program's success is a crucial step toward further validating outcome measures that will support subsequent clinical research and market authorization. Prof. Dr. Smeitink extended thanks to the patients, their families, clinical study teams, and patient advocacy groups for their contributions to this program.

Insights gained from the Phase 2b program, in conjunction with data from two earlier short-term safety studies, have provided a comprehensive foundation to optimize the design of Khondrion’s upcoming pivotal Phase 3 study. This future study will delve deeper into the potential of sonlicromanol for m.3243A>G PMD patients.

Khondrion is at the forefront of developing therapies for PMD, and sonlicromanol is one of the most advanced drug candidates in this field. The drug has been tested in several clinical trials involving patients with the m.3243A>G mutation and in a 6-month Phase 2 study in children with genetically confirmed PMD and motor symptoms. Sonlicromanol has also received orphan drug designations for treating MELAS syndrome, Leigh disease, and maternally inherited diabetes and deafness (MIDD) in Europe, and for inherited mitochondrial respiratory chain disorders in the US. Additionally, it has been granted a rare pediatric disease designation in the US for MELAS treatment.

Primary mitochondrial disease occurs when mitochondria, which are responsible for cell energy production, malfunction. This can lead to various severe and debilitating illnesses, manifesting from birth or later in life, with symptoms like cognitive issues, learning disabilities, blindness, deafness, heart failure, diabetes, fatigue, and muscle weakness. The m.3243A>G variant includes a spectrum of phenotypes, such as classic MELAS, MIDD, mixed phenotypes (MP), and chronic progressive external ophthalmoplegia (CPEO).

Khondrion continues to work towards developing effective treatments for PMD, aiming to improve the lives of patients affected by this challenging condition.