Khondrion’s mitochondrial disease candidate has missed the mark in a phase 2b clinical trial. But the Dutch biotech, clutching post hoc analyses and long-term follow-up data, plans to advance into the next stage of development anyway in the belief the totality of the evidence supports further work.
The drug candidate, sonlicromanol, is an intracellular redox-modulating small molecule in development as a treatment for primary mitochondrial disease. According to Khondrion, sonlicromanol targets the underlying mechanisms of mitochondrial disease through its triple mode of action, which includes reducing levels of cellular reactive oxygen species and restoring the redox balance.
Khondrion put that idea to the test in a phase 2 clinical trial that randomized 27 people with a specific confirmed mitochondrial DNA mutation and with clinical signs of mitochondrial disease to receive one of two doses of sonlicromanol or placebo orally twice a day.
After 28 days, participants in the sonlicromanol arm performed no better on the attention domain score of cognitive functioning than their peers on placebo, causing the study to miss its primary endpoint. An earlier phase 2 clinical trial found no significant improvements in gait parameters, leading Khondrion to focus on other aspects of mitochondrial disease in its next study.
While the second study missed its primary endpoint, Khondrion again found sources of optimism in the data. The biotech pointed to “positive trends” in post hoc analyses of other cognition and mood-related endpoints and in other domains including fatigue. Participants taking sonlicromanol performed better on a depression scale and cognitive failure questionnaire.
Khondrion also pitched data on the seven subjects in its 52-week open-label follow-up study as a positive for the prospects of sonlicromanol. All participants received the higher of the two phase 2b doses, and “the majority of subjects showed a meaningful improvement” on the NMDAS mitochondrial disease scale. Khondrion reported decreases of up to six points, versus a 0.47-point increase in a historical study.
According to Khondrion, the “more pronounced treatment effects” after 52 weeks are in line with expectations for the slowly progressing rare diseases. Yet, the small size of the follow-up study and lack of a control arm leave scope to question the strength of the findings.
The biotech is sufficiently enthused by the data to talk up its prospects of moving sonlicromanol into a phase 3 clinical trial. Khondrion plans to talk to U.S. and European regulators with a view to starting the study late next year.