MDA 2024: Vatiquinone may help extend FA patients’ ability to walk

Better balance, longer standing ability seen for those on therapy in trial

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The abbreviation MDA, for Muscular Dystrophy Association, is shown against a backdrop of scattered prescription medicine capsules.

Treatment with vatiquinone significantly slowed declines in upright stability among children and young adults with Friedreich’s ataxia (FA) in a clinical trial, leading researchers to predict it could delay the loss of patients’ ability to walk (ambulation) by about nine months.

While the MOVE-FA clinical trial failed to meet its main goal of achieving a significant slowing of overall disease progression with vatiquinone, its team of researchers now suggest that the findings of some new analyses may ultimately be more important for patients.

The researchers noted that the evaluation of upright stability might be a more sensitive measure to capture meaningful changes that might predict ambulation loss or preservation in this group — especially given that preserving the ability to walk is a key goal in FA management.

The findings of the analyses were detailed in a poster titled “Improvement in Upright Stability subscale of mFARS with Vatiquinone Treatment in MOVE-FA: a Phase 3, Double-blind, Placebo-controlled Trial.” The poster was presented at the Muscular Dystrophy Association’s MDA Clinical & Scientific Conference, held last week in Florida and virtually.

Vatiquinone is a small molecule designed to enter the brain and block activity of 15-lipoxygenase, an enzyme involved in signaling pathways that control neuroinflammation and oxidative stress, a type of cellular damage that’s implicated in FA.

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Fatigue, upright stability improvements seen in MOVE-FA

The Phase 2/3 MOVE-FA study (NCT04577352) enrolled 146 FA patients, ages 7 and older, who retained their ability to walk short distances with or without assistance and who could swallow capsules. The participants were randomly assigned to receive oral vatiquinone capsules, at a weight/age-based dose, or a placebo three times daily for 72 weeks, or about 17 months.

The trial’s main goal was to determine whether vatiquinone significantly slowed disease progression relative to the placebo among 7- to 21-year-old ambulatory patients, as assessed by changes in overall scores on the modified Friedreich Ataxia Rating Scale (mFARS).

While vatiquinone slowed mFARS progression by 1.6 points compared to the placebo in these patients, the difference was not statistically significant and the trial failed to meet its main goal.

The treatment did, however, demonstrate a significant benefit relative to the placebo in terms of fatigue reduction and function in the upright stability subscale (USS) of the mFARS.

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Balance is key to ability to walk, researchers note

Data from the FA Clinical Outcome Measures Study (FACOMS) — the largest existing natural history database of FA patients — indicate that the USS, which measures functions related to balance, stance, and mobility, is the main driver of declines in overall mFARS scores for ambulatory patients between the ages of 10 and 21.

That makes it a “relevant metric of disease progression in younger, ambulatory FA patients,” the researchers wrote.

When the team further explored changes in the USS among MOVE-FA trial participants, they found that USS was the only mFARS subscale where disease progression was observed in the placebo group after 72 weeks in the trial. In other measures, functions including the ability to speak and swallow (bulbar function) remained stable, as did upper limb and lower limb function. Those findings were consistent with the natural history of FA.

The USS captures specific tasks related to stance and balance that are mini-milestones of disease progression, with abilities lost in a defined pattern that precedes a person’s loss of independent walking ability.

An FA patient tends to first lose the ability to stand with the feet apart and eyes closed. Next, the ability to stand with the feet together is lost, followed by the loss of ability to stand with the feet apart and eyes open, and finally, loss of ability to walk.

Vatiquinone treatment delayed those first two milestones. Additional analyses of FACOMS data indicated that for each point preserved in the USS, the loss of walking ability is delayed by an estimated 6.9 months.

Vatiquinone treatment resulted in clinically meaningful and statistically significant treatment effects on [a key rating scale that is] a sensitive and predictive endpoint for risk of loss of ambulation, prevention of which is a key goal for therapy in ambulatory FA patients.

Applying that to the MOVE-FA participants, vatiquinone was found to slow the rate of USS declines by 0.8 points per year relative to the placebo. The 1.26-point difference between the groups after 72 months corresponds to about a nine-month delay in the loss of ambulation.

“Vatiquinone treatment resulted in clinically meaningful and statistically significant treatment effects on the USS, a sensitive and predictive endpoint for risk of loss of ambulation, prevention of which is a key goal for therapy in ambulatory FA patients,” the researchers wrote in the study abstract.

MOVE-FA participants who completed the main trial had the option to enter into an open-label extension phase, where all will receive vatiquinone for an additional six months.