Khondrion’s mitochondrial diseases treatment producing positive results

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Clinical-stage pharmaceutical company, Khondrion, discovering and developing therapies targeting primary mitochondrial diseases announced yesterday (November 22) its wholly-owned lead asset sonlicromanol for MELAS spectrum disorder has demonstrated positive treatment results.

MELAS spectrum disorder is a rare progressive mitochondrial disease and sonlicromanol will move into a phase 3 registrational study supported by favorable benefit-risk profile. The treatment will now move into a phase 3 development in MELAS spectrum disorders.

Both Khondrion’s randomized placebo-controlled phase 2b KHENERGYZE study and ongoing phase 2b open label extension KHENEREXT study show statistically significant and/or clinically meaningful results in multiple outcome measures with an acceptable safety profile.

Khondrion’s sonlicromanol progress

In line with previous studies, sonlicromanol was found to be safe and well tolerated in the phase 2b program, with no serious adverse effects. The overall evaluation of the shorter and longer term data from the program shows patient benefits in several domains (cognition and mood, pain, fatigue and balance control) and marked improvements in global health and quality of life assessments. This supports sonlicromanol’s progression into phase 3 clinical development in patients with MELAS spectrum disorders.

Khondrion says that while the 28-day phase 2b study did not meet its primary endpoint of the attention domain score of cognitive functioning, the study demonstrated positive treatment effects in several other cognition and mood-related secondary endpoints.

In line with expectations in these slowly progressing rare diseases, analysis of the data shows more pronounced treatment effects after 52 weeks. These longer-term patient data are, therefore, instrumental in providing valuable insights for the design of the upcoming phase 3 trial.

Mitochondrial disease innovation

Mirian Janssen, one of the principal investigators, Radboud Centre for Mitochondrial Medicine, the Netherlands, said: ‘’I am encouraged by these promising results, especially the improvement in quality of life measurements and NMDAS score over a longer period. The fact that the study-patients wish to continue using sonlicromanol and their personal motivation are also positive signs.

“I have had the privilege to work closely with many of these patients for many years and I am pleased to observe tangible improvements in those patients who have now been treated with sonlicromanol for 52 weeks. I praise Khondrion for its pursuit of mitochondrial disease innovation, care to the patients in its trials and commitment to this development program.”

Details of the KHENERGYZE phase 2b study in adults with MELAS spectrum disorders involved 27 patients treated with sonlicromanol (50 mg and 100 mg bid) for 28 days showed that it did not achieve a statistically significant improvement in the attention domain score of cognitive functioning, as assessed by the computerized Cogstate visual identification test, compared to those who received placebo.

Khondrion notes meaningful improvement

Post-hoc analyses of the study data showed positive trends in several other cognition and mood-related secondary endpoints as well as in other domains including fatigue. More specifically, statistically significant and clinically meaningful treatment effects versus placebo were obtained, amongst others for the Beck Depression Inventory (BDI) and the Cognitive Failure Questionnaire (CFQ). The totality of data suggests better effectiveness of the 100 mg bid dose relative to 50 mg bid. An acceptable safety profile was confirmed.

The KHENEREXT phase 2b, the open label extension study is ongoing. An interim analysis from the study, examining the long-term safety and a broad set of efficacy parameters of sonlicromanol (100 mg bid) in patients who completed the KHENERGYZE study, confirmed the positive results shown in the phase 2b study on BDI and CFQ over a longer period of time in a first cohort of seven patients who received sonlicromanol for 52 weeks.

Khondrion said that on the widely-used NMDAS score, specifically developed and validated to assess disease severity of adult patients with primary mitochondrial disease, the majority of subjects showed a meaningful improvement with a decrease up to 6 points after 52 weeks. An acceptable safety profile was confirmed.

Important milestone for Khondrion

Jan Smeitink, chief executive officer at Khondrion, said: “These results are an important milestone for Khondrion. While sonlicromanol’s effect on the primary endpoint within a 28-day period was insufficient in the phase 2b trial, we believe the broader results from the phase 2b program, now up to 52 weeks, provide unequivocal evidence of the positive clinical impact and important patient benefit that sonlicromanol can provide.

“We are particularly encouraged by the positive signals on overall disease severity, mood, cognition, fatigue, balance and pain, all belonging to the most burdensome symptoms patients experience in their daily lives, as mentioned in UMDF’s Voice of the Patient Report 2019. We look forward to discussing our plans with European and U.S. regulators in the near future, ahead of the initiation of the phase 3 registrational trial which is currently foreseen in late 2023.

“I would like to express my heartfelt gratitude to each of the patients, and their families who have played a part in these studies, and to the patient advocacy groups, the clinical study teams in Nijmegen, Munich, Newcastle and Copenhagen, and Foundations and Governmental bodies for their special contributions to our research. And a huge thank you to the talented team at Khondrion for their continued hard work, furthering this field of research, and for their commitment to finding the new treatments that are so needed for patients.”

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