The RENEO studies were among the first clinical trials exploring a potential treatment for primary mitochondrial myopathy, a form of mitochondrial disease that mainly affects the muscles and currently has no approved disease-modifying treatments.

For patients, this was an important milestone. For the first time ever, people with primary mitochondrial myopathy had the chance to contribute to research testing whether a new treatment could be safe – and whether it could improve symptoms.

A recent paper published in Scientific Reports shares results from an early-stage study of mavodelpar, (also known as REN001), part of a wider programme sponsored by Reneo Pharmaceuticals.

In this Research Zone article, we look at what those results mean, why promising early findings need to be tested in larger studies, and why participation still matters – even when a treatment doesn’t go on to reach patients.

What did the early trial find?

Primary mitochondrial myopathy can cause symptoms such as:

• Fatigue
• Muscle weakness
• Pain
• Difficulty with exercise

These symptoms can significantly affect quality of life and independence.

Mavodelpar was developed to improve how muscles use energy – particularly how they process fats as a fuel source. Researchers hoped this might help muscle cells work more efficiently to improve symptoms.

The paper reports on a Phase 1b trial, an early-stage study focused mainly on safety and tolerability: in simple terms, whether people could take mavodelpar without unacceptable side effects.

23 people received mavodelpar and 17 completed the first 12 weeks of treatment. A longer extension study was planned but stopped early due to COVID-19.

Key findings

• The treatment was generally well tolerated
• Most side effects were mild or moderate (e.g. headache, constipation), each reported by four of the 23 participants
• No serious treatment-related side-effects were reported

Although safety was the main focus, the trial also looked at several exploratory measures, including walking distance, exercise testing, fatigue, quality of life, pain, blood markers and muscle biopsy results. Some of these measures appeared to improve after 12 weeks.

Taken together, the results were encouraging enough to support testing mavodelpar in a later, more rigorous trial.

Why was further evidence needed?

Early trials aren’t designed to prove a treatments works – they’re designed to test safety. This study had important limitations:

• Small number of participants
• No placebo (comparison) group
• Everyone knew they were receiving the treatment

This matters because:

• Fatigue and pain can naturally vary over time
• People may perform better on repeat tests
• Being in a trial can influence how people feel or report symptoms

So while improvements were real for participants, researchers couldn’t be 100% sure they could be attributed to the treatment.

What happened next?

The early results led to a larger, Phase 2b trial, designed to test whether mavodelpar provided clear clinical benefit. However, this later study didn’t meet its main goal because it didn’t show sufficient effectiveness of mavodelpar, and this led to the development programme being discontinued.

This is understandably disappointing for the mitochondrial disease community, particularly for those who gave up their time to take part. However, it highlights an important point – promising early results don’t always translate into real-world treatments.

A treatment can be based on sound science and still not show benefit when tested more rigorously. This is especially true in rare and complex conditions such as mitochondrial disease.

What can we learn from the RENEO studies?

Even though mavodelpar didn’t succeed, the studies provide valuable insights:

• Rare diseases are complex – Primary mitochondrial myopathy is rare, and varies widely between individuals, making trials harder to design.
• Measuring success is challenging – Improvements in walking or fatigue matter to patients, but they must be proven to come from the treatment.
• Biomarkers need improvement – These gave mixed results and didn’t clearly show consistent improvements in mitochondrial function.
• Trial design needs to evolve – Future studies need better outcome measures, more reliable biomarkers and designs suited to smaller patient populations.

These lessons help improve future research, even when one treatment doesn’t succeed.

Why participation still matters

Clinical trials depend entirely on people being willing to take part. In the RENEO studies, participants helped researchers:

• Understand the safety of mavodelpar
• Explore how to measure symptoms like fatigue and mobility
• Determine that the treatment did not provide enough clinical benefit in the end

Although the outcome wasn’t the one people had hoped for, it’s still important. It helps avoid further time and resources being spent on ineffective treatments and helps shape how future studies should be designed.

The need for effective treatments for mitochondrial disease remains urgent and the outcome of the RENEO studies doesn’t change that. If anything, it reinforces the importance of continued investment in clinical trial readiness, better outcome measures, reliable biomarkers and meaningful patient involvement.

For The Lily Foundation, the patient voice remains central to this process. People affected by mitochondrial disease should help shape research priorities, trial design, outcome measures and how results are communicated. This is essential if future trials are to measure what matters most to patients and families.

If you’d like to read more about the RENEO trial, you can read the full accepted manuscript here. Please note that this is an accepted manuscript published online by Scientific Reports.