Biotech company Abliva is now preparing for the perhaps biggest step in the company’s history to date – a pivotal phase II/III study with the main candidate KL1333. When designing the study, the company has worked together with several patient organisations to gain a deeper understanding of the patients’ reality.

Lund-based Abliva’s pipeline includes two candidates targeting primary mitochondrial diseases, KL1333 and NV354, both of which have shown encouraging results. KL1333 is being developed for the treatment of mitochondrial disease in adults and is the furthest advanced of the two candidates.

Significant medical need

Primary mitochondrial diseases affect the ability of cells to convert energy and can lead to several severe symptoms. Muscle weakness, chronic fatigue and exercise intolerance are the most common symptoms, while those who are most severely affected also experience life threatening symptoms such as stroke-like episodes and heart failure. In a previous article, BioStock described what everyday life can look like for a patient with mitochondrial disease. Today, there are only a few available treatment options, mostly supplements and vitamins, and the medical need for mitochondrial disease is extensive.

The patients in focus

In June, Abliva conducted a financing round of 200 million SEK, the proceeds of which are focused on the pivotal phase II/III study with KL1333.

When designing the study, extensive work has been done by Abliva to understand the mitochondrial disease patients’ experiences in order to select relevant and sensitive outcome measures, and patient organisations have played a major role in this process. Among other things, in 2021, Abliva conducted a large interview study where the company received assistance with patient recruitment from the US patient organisation United Mitochondrial Disease Foundation (UMDF). Since 1996, UMDF has brought patients together and worked to increase knowledge and awareness of mitochondrial disease.

The interview study included 14 participants in the United States suffering from primary mitochondrial disease, aged between 20 – 75 years old. In the study, the patients talked about how the disease affects their everyday lives.

As part of the work to gain an in-depth understanding of patients’ perspectives, Abliva has also participated in several of UMDF’s patient meetings, presented at the Italian organisation Mitocon’s conferences and attended many other events such as World Mitochondrial Disease Week, Bioblast and mitoNice.

Chronic fatigue – the most challenging symptom for a majority of patients

Along the way it has become clear that chronic fatigue, which is common among patients with mitochondrial disease, is an important symptom to address. Chronic fatigue means that the patient suffers from chronic and extreme fatigue with a lack of both physical and mental energy. The symptom is very common and can affect sufferers daily; for many patients the situation worsens as the disease progresses.

Chronic fatigue can affect physical and mental capacities such as the ability to work, study, perform everyday activities, and enjoy life. Once occurring, the fatigue rarely improves and the severity gradually worsens as the overall disease progresses.

Number two on the list of symptoms that patients wished the pharmaceutical industry would address was muscle weakness. Muscle weakness also commonly limits the patients’ abilities to perform everyday activities.

Study designed with patient focus

The outcome of the collaborations with patient organisations and Abliva’s own patient interviews is that the clinical trial with KL1333 will now focus on the symptoms that truly are the most debilitating for the patients and will evaluate the effect of KL1333 on relieving the symptoms.   

The candidate has previously been evaluated in both healthy volunteers and patients with good results. Last year, the FDA approved Abliva’s IND application for KL1333, making it possible to start a pivotal phase II/III study.  Since then the company has received additional country approvals and the study is still on track to start later this year.