Early clinical trial shows promising results for adults with primary mitochondrial disease

Rare diseases impact around 300 million people globally, but only 5% have approved treatments. Despite increased interest in developing drugs for these diseases, challenges such as small sample sizes, incomplete understanding of disease progression, and lack of reliable outcome measures hinder progress. This is particularly true for primary mitochondrial diseases (PMDs), which remain without approved therapies. PMDs are a group of genetic disorders that affect the energy-producing structures within cells (mitochondria), leading to muscle weakness, fatigue, developmental delays and neurological issues.

The current study, published in Brain, was a double-blind, randomized, placebo-controlled, single and multiple oral dose phase 1a/1b study. The study investigated the safety and tolerability of KL1333, a novel oral molecule that balances certain chemicals in the body that are essential for producing energy.

Sixty four healthy volunteers were recruited to the study, in addition to eight people living with PMD. The participants were recruited by teams led by Professor Robert Pitceathly, at the UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, and Professor Gráinne Gorman, from the Wellcome Trust Centre for Mitochondrial Research in Newcastle. Of the 74 total participants, 54 received KL1333 (six with PMD) and 18 received the matched placebo.

The researchers found noticeable differences between the KL1333-treated and the placebo group; those with PMD who received KL1333 reported less fatigue and showed increased functional strength over ten days.

Results also indicated that KL1333 was safe and well tolerated, with dose-dependent gastrointestinal side effects.

Senior author, Professor Robert Pitceathly, said: “This study represents an important step towards developing a therapy for mitochondrial diseases, a common cause of inherited neurological disorders for which no treatment exists in most instances. It also demonstrates the power of thoughtful trial design, when informed by people living with rare conditions, during the early clinical stages of drug development.”

Lead author, Dr Chiara Pizzamiglio, UCL Queen Square Institute of Neurology said “Fatigue is a disabling and common symptom for those living with PMDs, and this early-stage clinical trial indicates promising results for KL1333.

“Throughout the trial, the voice of patients was central. We worked with those living with PMD to develop relevant and clinically meaningful outcome measures, and the results from this trial have guided the selection of primary end points and inclusion criteria for the ongoing phase 2 efficacy trial.”

Chief Medical Officer of Abliva, Magnus Hansson, said: “A publication in a prestigious journal like Brain highlights the importance of these findings and validates the adaptive trial design, which has informed Abliva’s ongoing Phase 2 FALCON study of KL1333 in primary mitochondrial disease.

“We believe it is important to involve patients early, especially in rare disease studies, and we look forward to advancing KL1333 through clinical development as expeditiously as possible.”

Related:

• Source: adapted from Abliva's press release
• Study in Brain: Optimizing rare disorder trials: a phase 1a/1b randomized study of KL1333 in adults with mitochondrial disease 
• Dr. Chiara Pizzamiglio's academic profile
• Professor Robert Pitceathly's academic profile

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