FDA clears Khondrion's IND application for Phase 3 trial of sonlicromanol for primary mitochondrial disease

Khondrion, a biopharmaceutical company focused on developing treatments for primary mitochondrial disease (PMD), has announced that it has received the green light from the U.S. Food and Drug Administration (FDA) for its Investigational New Drug (IND) application for sonlicromanol. This approval paves the way for a pivotal Phase 3 clinical trial to investigate the efficacy of sonlicromanol in adult patients suffering from PMD caused by the m.3243A>G mutation.

The upcoming Phase 3 trial, which is expected to start in 2025, aims to further validate the promising results observed in prior studies of sonlicromanol. This drug candidate is a first-in-class, brain-penetrant redox-modulator with anti-inflammatory properties that targets key metabolic and inflammatory pathways implicated in PMD. The trial will be a double-blind, randomized, placebo-controlled, multi-center study, expected to enroll 150 adult patients with a genetically confirmed m.3243A>G variant in their mitochondrial DNA.

This mutation is the most common genetic defect causing PMD, a condition characterized by chronic fatigue and muscle weakness. These two symptoms will serve as the primary endpoints for the Phase 3 trial, assessed using the Neuro-QoL Fatigue short form questionnaire and the Five Times Sit-to-Stand test. The Phase 2b program of sonlicromanol has already shown significant patient benefits, including improved outcomes in these areas.

Prof. Dr. Jan Smeitink, Khondrion’s Chief Executive Officer, expressed enthusiasm over the FDA’s clearance, emphasizing the importance of sonlicromanol as a potential disease-modifying therapy for PMD. He noted the company’s anticipation of sharing further progress as they prepare to initiate the trial next year.

Sonlicromanol has been evaluated in four clinical trials, including three involving adult PMD patients with the m.3243A>G mutation and one in children with genetically confirmed PMD. The drug has demonstrated a favorable safety profile, as evidenced by patients in the Netherlands who have been on sonlicromanol for over two and a half years following the Phase 2b open-label extension study.

Khondrion’s dedication to advancing treatments for PMD is further underscored by sonlicromanol’s designation as an orphan drug in both the U.S. and Europe, and its receipt of a rare pediatric disease designation in the U.S. The company is initially targeting PMD patients with the m.3243A>G variant but aims to eventually broaden the availability of sonlicromanol to the wider PMD patient community.

PMD is a group of inherited neurometabolic disorders that affects a significant number of individuals, with an estimated prevalence of at least 1 in 4,300 in the U.S. alone. The condition arises from defective mitochondria, the energy-producing components within cells, leading to a range of severe and debilitating symptoms. These can include cognitive issues, motor dysfunction, fatigue, muscle weakness, and other multisystemic problems.

Khondrion remains committed to developing therapies that address the underlying causes of PMD and improve the quality of life for those affected by this challenging condition.