Highlighting the Significant Strides Made in Friedreich Ataxia Care

David R. Lynch, MD, PhD

Among the notable presentations at this year’s International Parkinson and Movement Disorder Society (MDS) Virtual Congress, September 17-22, one highlighted the benefits omaveloxolone (Reata Pharmaceuticals) treatment in patients with Friedreich ataxia (FA). The findings, presented by David R. Lynch, MD, PhD, professor of neurology, University of Pennsylvania Perelman School of Medicine, were from the delayed-start assessment of the MOXIe trial (NCT02255435), the largest study of FA to date.

At the end of the 48-weel placebo-controlled period, patients treated with the investigational agent showed a difference of –2.18 (±0.96) points in modified Friedreich’s Ataxia Rating Scale (mFARS) scores compared to placebo. These results were preserved at the end of the 72-week open-label delayed-start period (–2.92 [±2.13]). The persistent effect of omaveloxolone in this patient population has garnered the attention of clinicians within the field, including Lynch, who believes this could potentially be the first FDA-approved drug for the disease.

Lynch sat down with NeurologyLive to discuss how they plan to further cement their results, the progress made within the field, and what is still be done. He also provided his takeaways from MDS 2021, and the phenomenon surrounding gene therapy and its place within movement disorders.

NeurologyLive: What types of research are important to understanding more about omaveloxolone?

For omaveloxolone, the key thing moving forward is that this study was performed in individuals of 16 to 40 years of age, and there are no safety data of any degree in children to this point. The most important thing will be to see to if it transitions well to children and has some benefit there. If the dosing can be identified, this is just one way to counteract the deficiencies of frataxin. The next step, while we use omaveloxolone, is to find ways to restore frataxin, whether that’s turning the mutant gene back on, which is more than a theoretical possibility, or through protein-based therapy or gene therapy. Those combined approaches are very attractive toward eventually finding a situation where Friedreich ataxia can be essentially stopped or cured.

Can you describe the current knowledge of the disease? What progress has been made thus far?

That’s an interesting question because 23 years ago, when we started this work, the disease was in some ways on its surface very simple. A single protein deficiency which goes to the mitochondria. This should be straightforward. But of course, nothing is ever as simple as it looks. We’ve made an incredible amount of progress in understanding what frataxin does and doesn’t do, ways to restore it, and the downstream pathways. In addition, with the help of the Friedreich’s Ataxia Research Alliance, we’ve made a lot of progress on coming up with measures that can help define the disease, as well as new biomarkers to see what we’re reversing biologically. Now, it’s purely the drug development, which lacks at identifying drugs and bringing them forward for testing. The background is not completely defined, but I think we’ve made enough progress to where we’re ready to move forward in many ways.

What is your biggest takeaway from this year’s MDS Virtual Congress and the direction the field is headed?

For the field in terms of FA research, the most important thing is that we now have reached the era of clinical trials and possible successful development. There’s a big emphasis shown across multiple presentations on how we’re now trying to address rare diseases, not just common diseases like Parkinson disease. Now there’s enough interest in rare disease where it can truly move forward. That’s something which, if you go back 20 years, we were not prepared to do. Collectively, across all the fields, people are doing much better at it now.

Which ongoing therapeutic development are you most excited for in the movement disorder space?

At this point in my career—which I’ve been in for about 35 years—I’ve become very focused on Friedreich ataxia, and I think the area we’re most interested in is gene therapy. Can it be made successful? It works great in mice, but people aren’t mice. It’s a lot more difficult and there will be pragmatic questions that not only involve scientific approaches, but ethical approaches and where to go. That’s something we need to concentrate on to understand, what are the appropriate things to consider? And, what are the appropriate ages? Additionally, what are the appropriate levels of affectation in which we target risky therapies like gene therapy?

Transcript was edited for clarity.

REFERENCE

Lynch DR, Chin MP, Boesch S, et al. Efficacy of omaveloxolone in patients with Friedrich’s ataxia: delayed-start study. Presented at MDS Virtual Congress; September 17-22, 2021. Poster LBA 2.