Over about two weeks, more than 74,000 people worldwide have signed a petition from the Friedreich’s Ataxia Research Alliance (FARA) requesting that omaveloxolone (omav) be made available to people with Friedreich’s ataxia (FA) as quickly as possible.
The petition specifically asks Reata Pharmaceuticals to submit a new drug application (NDA) for omaveloxolone to the U.S. Food and Drug Administration (FDA) on an urgent basis, and that the regulatory agency consider its approval based on existing evidence.
This “call to action” — backed by patients, family members, friends, and FA experts from 118 countries — drew on data from the MOXIe Phase 2 trial (NCT02255435), a two-part study with a long-term extension investigating the safety and efficacy of omaveloxolone in 172 FA patients, ages 16 to 40.
While the primary endpoint of improved neurological function was met, the FDA still determined that the results were not enough to support omav’s approval, leaving open the possibility of a future approval, pending confirmation of benefits in an additional clinical study.
With no treatments currently available for this rare disease, however, FARA argues in its petition that the improvements in neurological function and in activities of daily living after nearly one year of use, coupled with the compound’s favorable safety profile, are sufficiently meaningful in the lives of people with FA to warrant approval.
A key concern raised by FARA is “how robust of a finding in those trials must there be” to secure a favorable FDA decision. The organization asks for clarity from the agency in defining the bar for evidence required for approval, and the number of clinical trials needed.
“We recognize that these are complex questions, which may not have a one size fits all response as different therapeutic interventions will have different risk benefit profiles,” FARA said to Friedreich’s Ataxia News.
“We would like to understand when the FDA is willing to consider applying the flexibility provided by the regulations, to allow for single and adequate well-controlled trial with significant results in a rare disease with unmet medical need,” the organization added.
Reata promptly responded to the petition. “We share your perspective that omaveloxolone is a promising potential treatment for FA,” the company said in an open letter to the FA community, adding that it “will continue to seek a constructive dialogue with the FDA” concerning the possibility of future approval.
“We are prepared to complete the preparation of and to submit a new drug application for omaveloxolone, if the FDA indicates that the clinical trial package would support their review,” the letter continued. “Also, we are prepared to conduct a follow-on study to expand and further bolster the body of evidence supporting omaveloxolone as a potential therapy in FA.”
FARA expressed gratitude for Reata’s “prompt attention and response to the FA community’s petition” and for its commitment to “securing the regulatory approval necessary to make omaveloxolone available to patients with FA.”
But in the meantime, “FA is a progressive disease, and there are currently no approved therapies to treat the condition,” FARA said. “As more time passes, there will be more progression of FA symptoms.”
Even effects that seem small in a clinical trial can profoundly influence a person’s life.
Shandra Trantham, a third-year doctoral student in the Genetics and Genomics Graduate Program at the University of Florida, understands this on a personal level. She participated in part 1 of MOXie, and is currently enrolled in its open-label extension part.
Trantham was diagnosed with FA at age 12, although she began noticing the symptoms three years prior.
“I was in gymnastics and I couldn’t walk on the balancing beam anymore,” she said in an interview with Friedreich’s Ataxia News. “From that, I just got progressively more symptoms.”
Adapting to life with FA came to include using a walker; recording class notes on her phone, as she cannot write notes quickly; and working with a lab tech to perform techniques that require fine dexterity.
Trantham entered the MOXie study in 2015, her first clinical trial. While she did not experience any noticeable changes at the time, she could have been receiving placebo or one of the lower doses of omaveloxolone. “I have no idea what I was on,” she said.
This ambiguity began to change soon after entering its open-label extension in 2019.
“I started noticing benefits in how I was feeling pretty immediately, but obviously I was hesitant to believe that they were actually effects, because I knew that I was taking the real medication, so I might have been making it up in my head,” Trantham said.
Trantham said she felt more stable and that her walking improved, but she retained a measure of skepticism. Fortunately — whether by design or accident — she incorporated a measure of scientific control into her own experience with omaveloxolone, by not telling her mother that she was being treated with an investigational medicine.
“She saw me walking to the car and she was like, ‘What are you doing, you’re walking a lot better.’ And I knew then that I wasn’t just imagining it, because she had noticed and she didn’t even know I was doing the trial,” Trantham said.
Since then, improvements in Trantham’s ankle stability have led her to change from high-top to low-top Converse shoes, and she describes consistently having more energy to work with throughout her day.
“Before I was taking omaveloxolone, I would go to the grocery store, and immediately after coming home, I would need to lie down,” she said. Now, “after being at school and work all day, I come home and I feel fine.”
To Trantham, however minor they may sound, these improvements are the difference between maintaining an accustomed level of comfort or watching it slip away.
Trantham becomes even more aware of them when she sees friends with FA a couple times a year. “I know that every time I see them, they progress a lot, and … if I look at myself, I’m really not progressing,” she said.
“I think that’s because of omav,” she added. “And that’s great for me, but … terrible that my friends don’t have access this medication that could be doing the same thing for them.”
To FARA, experiences like Trantham’s reflect the human value of the average 2.4-point improvement in the modified Friedreich’s Ataxia Rating Scale (mFARS) scores recorded in the MOXie trial. And with no significant safety concerns related to the medication, the organization questions why access shouldn’t be granted.
Healthcare professionals active in the FA community — including neurologists, geneticists, and cardiologists — provided a letter of support to accompany FARA’s petition. In it, they expressed their own concern for the potential damage done by waiting for better results, particularly given the challenges in conducting clinical trials for disorders as rare as FA.
“We don’t believe it is feasible to conduct additional placebo-controlled trials of omav in the United States due to complications of the current pandemic and the limited number of patients available,” they wrote.
“We write to support FARA’s request to Reata to submit a New Drug Application (NDA) on an urgent basis and FDA to exercise the flexibility granted by law and contained in FDA guidance in considering approval of an NDA for Omav in FA based on the existing evidence from clinical trials,” these doctors added.
To Trantham, there’s both safety in omav and the potential for a better future.
“We should be allowed to have access a drug that doesn’t have any adverse side effects and could possibly be effective, because even if it’s not effective, I’d rather waste my money and do something that is probably effective than not spend my money and wait for another trial,” Trantham said.
“Time is neurons and is progression of the disease,” she added. What you lose “you can’t get back.”
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