March 2023 Update: SKYCLARYS™ (Omaveloxolone) has become the first FDA-approved treatment for Friedreich’s Ataxia. You can learn more about SKYCLARYS™ at this link. This Snapshot was written in May 2020 after initial positive results were shared about Omaveloxolone.
A new therapeutic compound shows promise to treat Friedrich’s ataxia.
What is Friedrich’s ataxia (FA)?
Friedrich’s ataxia is a genetic neurodegenerative disease that affects many organs, most notably nerves, muscles, and heart. FA is a recessive ataxia. Symptoms typically present in childhood and result in significant physical disability. Cognition (thinking, memory) remains intact.
Some of the symptoms a person with FA may experience include ataxia (loss of movement coordination), fatigue, muscle weakness, cardiomyopathy (heart issues), scoliosis (curvature of the spine) and sensory impairments (vision, hearing). Life expectancy is reduced as a result of the disease.
The genetic change that is present in FA affects the production of a protein called frataxin. Frataxin deficiency leads to abnormal iron accumulation in mitochondria. As mitochondria are critical for energy metabolism and other important functions in cells, their dysfunction causes faulty energy production and undesirable toxicity in the form of reactive oxygen species.
There is currently no treatment available to patients with FA.
How does Omaveloxolone work?
Omevaloxolone is a synthetic compound. It works by counteracting deficits seen in disease at the cellular level. Omevaloxolone promotes Nrf2, which works to activate a series of defence mechanisms that help cells handle oxidative stress (mentioned above). Nrf2 is also important for improving the energy production machinery mitochondria require to function efficiently. Thus, by activating Nrf2, Omevaloxolone is thought to mitigate oxidative damage, improve energy production, and promote neuroprotection. Additionally, Omevaloxolone and similar compounds exhibit anti-inflammatory action.
What exactly has been validated?
In the MOXIe clinical trial, study participants with FA from several countries were randomized to either daily omaveloxolone (drug) or placebo (control). Their neurological function, activities of daily living, and ataxia were assessed at baseline (at the beginning) and after 48 months of receiving treatment. At the end of this period, the data showed statistically significant improvement in each of these measures. Participants who received omaveloxolone fared better than those who did not (placebo). Additionally, participants who received omaveloxolone saw improvements after treatment compared to their own baseline at the beginning of the study.
What is happening next?
The next step in testing omaveloxolone is to have a long-term study to examine its safety (and any side effects) over the course of a few years. Instead of having a control group in this type of study, called an open-label extension, now everyone enrolled received the same amount of omaveloxolone. This study is already underway and is expected to be completed by 2022. There have been some modifications to the long-term safety study in response to COVID-19, but Reata doesn’t expect there to be a significant delay in their timelines.
If you would like to learn more about omaveloxolone, take a look at these resources by the Reata Pharmaceuticals and ClinicalTrials.gov. To learn more about Friedrich’s Ataxia, visit the Friedrich’s Ataxia Research Alliance website.
Snapshot written by Dr. Judit M. Pérez Ortiz and edited by Larissa Nitschke.