At Khondrion we are advancing the science of mitochondrial medicine for the benefit of patients and families living with mitochondrial disease.
how medicines are developed
Before a new medication (or drug) can be prescribed by doctors or other healthcare providers it has to be approved by medicines regulators such as the EMA (European Medicines Agency) or FDA (US Food and Drug Administration). For such approval, the new medication must first be tested in humans in order to understand if it is safe and if it is effective, in other words if the drug can treat a medical condition, or disease, without harming patients. This part of a new drug development is called clinical research, and follows earlier preclinical research which is performed on other subjects such as cultured cells or animals.
Clinical trials are well-planned studies in which the safety and effectiveness of a new medication is compared to a placebo, i.e., a lookalike “pill” with no medication in it. In order to obtain objective results and interpretations, the studies are also double-blinded (or coded) meaning that neither the people giving the treatment nor the people receiving the treatment know who is getting the new medication or the placebo. Studies have a specific time duration defined by the investigators and when completed, the data are “unblinded” (or decoded) to reveal who has received the new medication or the placebo.
progressing our investigational medicines
At Khondrion our priority is to take the path which best ensures the rapid development of our pipeline, so we can deliver the much needed, transformative medicines to treat patients living with mitochondrial disease. Clinical trials enable the controlled testing of investigational medicines in defined patient populations to establish their safety and efficacy. We believe it is in the best interests of patients to progress our pipeline through a robust clinical trial process, that will enable us to be confident about the safety and efficacy of our compounds, gain regulatory approval and enable patient access as quickly as possible.
The safety and efficacy of our lead drug candidate, sonlicromanol, are currently being established in our Phase IIb KHENERGYZE clinical trial in adult patients with MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) spectrum disorders and our Phase II KHENERGYC clinical trial in children with a genetically confirmed primary mitochondrial disease and suffering from motor symptoms. The completed Phase IIa KHENERGY study generated consistent pharmacokinetic, safety and tolerability data and sonlicromanol demonstrated significant cognition-related patient improvements. We hope our further studies will enable us to learn more about the safety of this potential medicine and confirm its treatment effect on mitochondrial disease-related symptoms before submission of our research to regulators.
We appreciate the urgent need for new mitochondrial medicines and understand that many patients and their families want to explore all treatment options, including investigational medicines that have yet to be reviewed and approved by regulators. Khondrion does not currently have a compassionate use programme in place for sonlicromanol. Although we have seen early indications of its potential impact on the clinical symptoms of mitochondrial disease, these are from exploratory studies in a small number of adult patients. No safety or efficacy data in children or adolescents is currently available to show how it behaves in this patient group.
The results from our earlier studies have given us confidence to undertake further studies but these are highly controlled and in defined patient populations. We remain hopeful that these trials of sonlicromanol will show it to be a medicine that can bring benefit to patients who so desperately need new treatment options. We are working as quickly as possible to achieve this. We would encourage patients and families living with mitochondrial disease who are seeking more information about mitochondrial disease and available treatment and support options, to speak to their physician or local patient group. Some patient groups that we work with can be found below.
During this phase, the new medication is introduced to human beings for the first time. In the majority of cases the people receiving the drug, or participants, are healthy volunteers (in other words, people without a disease). The primary aim is to evaluate the safety and possible adverse effects of a new drug and therefore to determine a safe dosage that can be used in humans. During this phase investigators also study the pharmacokinetics of the drug, how fast it is absorbed, distributed, metabolized and excreted by and from the body, i.e., “what the body does to the drug”.
In this phase the effectiveness, safety and potential adverse effects of the new drug are evaluated on a small number of patients. These studies give the first indication as to whether the new drug works for the targeted disease. Optimal dosage (quantity and frequency) is also being determined during this phase. These studies are sometimes divided into Phase IIa and Phase IIb trials, where Phase IIa trials are specifically designed to assess dosing and initial efficacy, and Phase IIb trials further explore potential dosing options as well as the efficacy seen earlier in development.
Khondrion’s Phase IIa KHENERGY study was a double-blind, randomised placebo-controlled, study in 18 patients with a particular mutation in their mitochondrial genome and clinical signs of mitochondrial disease.
- Publication of the KHENERGY study results
The Phase IIb KHENERGYZE study further investigates the results from KHENERGY, evaluating dose-effect on cognitive functioning.
- First patients dosed in Phase IIb study of sonlicromanol for mitochondrial diseases
The first Phase II KHENERGYC study in children with movement disorders associated with primary mitochondrial diseases with a variety of genetic causes is ongoing.
Patients who have successfully completed the Phase IIb study in adults are offered to participate in the KHENEREXT study, a 12 months open label extension study to explore long-term tolerability, safety and efficacy.
[Link to press release – Khondrion announces first patients dosed in KHENEREXT Phase IIb extension study examining long-term safety and efficacy of oral sonlicromanol in mitochondrial disease patients]
When a new drug has been shown to be effective and safe enough during the Phase II trial it will then be tested in a large-scale study in an expanded patient population and at different geographical locations. This stage will further demonstrate the drug’s clinical efficacy, safety and optimal dosage.
This phase, also known as the post-marketing phase, takes place after the new medicine has been approved by medicines regulators such as the EMA or FDA. It is designed to further evaluate the long-term effectiveness and safety of the new drug on a large group of patients. Phase IV will also possibly compare the new drug’s cost-effectiveness to other drugs already on the market.
patient organisations we work with
To accelerate the discovery and development of our potential medicines for mitochondrial diseases, we work closely with patients and their families, and a network of patient organisations internationally, to ensure our research programmes are always focused on patients’ needs.