Skyclarys slows FA progression by more than 50% over 3 years: Study
Researchers compare treated patients with those in natural history study
People with Friedreich’s ataxia who were treated with Skyclarys (omaveloxolone) in the MOXIe trial and its extension for three years had more than 50% slower disease progression compared with patients in a natural history study, according to a new analysis.
“The present results show a meaningful slowing of [Friedreich’s ataxia] progression with [Skyclarys] over a period of 3 years and further support the findings observed in the MOXIe study,” researchers wrote.
The new study, “Propensity matched comparison of omaveloxolone treatment to Friedreich ataxia natural history data,” was published in the Annals of Clinical and Translational Neurology. The work was funded by Skyclarys’ developer Reata Pharmaceuticals, which was recently acquired by Biogen.
Skyclarys first FDA-approved treatment for Friedreich’s ataxia
Earlier this year, Skyclarys made history as the first treatment for Friedreich’s ataxia to be approved by the U.S. Food and Drug Administration (FDA). The daily oral therapy is designed to boost energy production in cells, which is expected to slow disease progression.
The FDA’s approval of Skyclarys was supported by data from a three-part clinical trial called MOXIe (NCT02255435). The trial’s second part tested Skyclarys against a placebo for one year in 103 participants, and results the showed that Skyclarys improved neurological function compared with a placebo.
This was measured with the modified Friedreich’s Ataxia Rating Scale (mFARS), a scale from 0 to 99 that rates neurological impairment in Friedreich’s ataxia, with higher numbers reflecting more neurological problems.
After the first year, participants in MOXIe had the option to continue receiving long-term Skyclarys treatment in the trial’s open-label extension part. The trial is still ongoing, and has found that Skyclarys continues to show benefits for up to three years of treatment.
In this study, scientists aimed to contextualize the long-term effects of Skyclarys compared to what would be expected without treatment. As doing a very long-term trial with a placebo wouldn’t be ethical, the researchers used an approach called propensity matching, in which participants from the trial were matched to patients with similar characteristics.
The scientists used data from the Friedreich Ataxia Clinical Outcome Measures Study (FACOMS; (NCT03090789), a study launched in the early 2000s that collected data on the progression of Friedreich’s ataxia in more than 1,000 patients who did not receive any disease-specific treatment.
From this database, the scientists identified individuals who had clinical and demographic features similar to participants in the MOXIe trial at the point when the trial began. With this strategy, the researchers matched 136 MOXIe participants with 136 patients in FACOMS, who were similar in terms of age, age at disease onset, sex, gait scores, and neurological function.
“Using this approach, the matched FACOMS group in the primary pooled population was highly comparable for demographics and baseline characteristics to the MOXIe extension patients,” the scientists wrote.
To compare disease progression, the researchers analyzed scores on the mFARS in both groups.
After three years, mFARS scores increased (worsened) by an average of 6.6 points for patients in the FACOMS registry. By comparison, among patients in MOXIe, treated with Skyclarys for a median of 2.76 years, scores increased by 3 points — which works out to a 55% slower rate of disease progression with Skyclarys.
Patients originally on placebo also had slower disease progression on Skyclarys
The effect was slightly more pronounced among patients who got Skyclarys in the original trial, who experienced a 61% reduction in the rate of progression in mFARS scores. Notably, patients who’d been on placebo for the first year then started on Skyclarys in the extension also had a significant reduction, of 56%, in disease progression over three years.
“During treatment in the MOXIe extension, [Skyclarys] treatment in the primary pooled population slowed progression by [more than] 50% at each year compared to the corresponding FACOMS external control group, indicating benefit that persisted and accrued over 3 years,” the researchers wrote.
Collectively, the results “demonstrate that treatment with [Skyclarys] provided a clinically meaningful slowing of [Friedreich’s ataxia] progression over a 3-year period compared to untreated, propensity score-matched FACOMS external controls,” the researchers concluded.
The scientists noted that any analysis like this, where participants in one study are compared with participants in a separate study, is inherently imperfect, because it’s impossible to fully match up patients from different studies.
“Although there are limitations to this cross-study analysis, the approach leads to readily interpretable results on the potential benefit” of Skyclarys, they wrote.