NIJMEGEN, The Netherlands, May 19, 2026
Khondrion announced that the first patient has been dosed in the Phase II SON4PEM clinical trial evaluating sonlicromanol for the treatment of debilitating fatigue associated with post-exertional malaise (PEM) in patients suffering from post-COVID syndrome. The milestone marks a major advancement in the company’s effort to expand sonlicromanol beyond primary mitochondrial disease into the growing long-COVID treatment landscape, where millions of patients worldwide continue to experience chronic fatigue, reduced physical function, cognitive impairment, and severe worsening of symptoms following even minor physical or mental activity. With no approved therapies currently available specifically targeting PEM-related fatigue in post-COVID patients, the SON4PEM trial positions Khondrion among a small group of companies attempting to address one of the most urgent unmet needs emerging after the global pandemic.
SON4PEM Trial Targets Severe Fatigue and Post-Exertional Malaise
The SON4PEM study is an investigator-initiated, randomized, double-blind, placebo-controlled Phase II clinical trial being conducted at Amsterdam University Medical Center with support from ZonMw, The Netherlands Organisation for Health Research and Development. The study plans to enroll approximately 80 adult patients diagnosed with post-COVID syndrome who continue to experience PEM, a disabling condition where minimal physical or cognitive exertion can trigger prolonged symptom worsening, extreme exhaustion, and loss of daily functioning.
Participants in the study will be randomized to receive either 90 mg sonlicromanol twice daily or placebo over a 13-week treatment period. The trial’s primary endpoint focuses on reduction in fatigue using the validated Fatigue Assessment Scale (FAS), while secondary endpoints will evaluate physical resilience, cognitive function, functional recovery, and broader quality-of-life improvements. According to Khondrion, the study is specifically designed around patient-centered outcomes intended to measure whether treatment can help individuals return to routine activities, employment, and social participation that are often severely disrupted by long-COVID symptoms.
Khondrion stated that sonlicromanol is a proprietary small-molecule redox modulator with anti-inflammatory properties that targets mitochondrial dysfunction and altered cellular stress responses increasingly associated with post-COVID syndrome. Scientific evidence has suggested that persistent mitochondrial impairment may contribute to chronic fatigue and impaired energy metabolism in long-COVID patients, making mitochondrial-targeted therapies an emerging focus area in post-viral disease research.
Growing Global Focus on Long-COVID Therapeutics
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Khondrion CEO Jasper Levink said the initiation of the SON4PEM study represents an important milestone both for the company and for patients facing limited treatment options. He emphasized that post-COVID syndrome continues to affect millions globally, with PEM remaining one of the most life-altering symptoms reported by patients. Levink added that even small improvements in fatigue and exertion tolerance could translate into meaningful gains in independence and everyday functioning.
Professor Michele van Vugt, Principal Investigator of the SON4PEM study at Amsterdam University Medical Center, noted that there are currently no approved therapies specifically targeting PEM in post-COVID syndrome, despite growing recognition of the condition’s impact on long-term health and productivity. She stated that increasing evidence linking mitochondrial dysfunction and inflammatory stress responses to long-COVID makes sonlicromanol a scientifically compelling investigational therapy deserving further clinical evaluation.
TProfessor Michele van Vugt, Principal Investigator of the SON4PEM study at Amsterdam University Medical Center, noted that growing scientific evidence increasingly implicates mitochondrial dysfunction in post-COVID syndrome, making sonlicromanol an important investigational approach worthy of further clinical evaluation. She added that the study is specifically designed around patient-centered outcomes focused on reducing fatigue and improving tolerance to everyday physical and cognitive activities.
The Phase II program also expands Khondrion’s broader clinical strategy surrounding sonlicromanol, which has previously been studied in patients with primary mitochondrial disease (PMD) and recently advanced into the pivotal Phase III KHENERFIN trial across Europe, the United Kingdom, and the United States. Sonlicromanol has additionally received orphan drug designations in both Europe and the U.S. for inherited mitochondrial disorders, along with a rare pediatric disease designation in the United States for the treatment of MELAS syndrome.
As healthcare systems worldwide continue addressing the long-term consequences of COVID-19, the SON4PEM trial could become an important study in the evolving effort to develop targeted therapies for chronic post-viral fatigue and mitochondrial-related disorders.
Source: Khondrion press release
