FDA requests more studies before approving vatiquinone for Friedreich’s ataxia

Key takeaways:

• Vatiquinone inhibits 15-Lipoxygenase, which regulates the pathways that Friedrich’s ataxia disrupts.
• PTC Therapeutics said it will work to address the issues raised by the FDA.

PTC Therapeutics has not provided substantial evidence that vatiquinone is effective in treating children and adults with Friedreich’s ataxia, the FDA told the company in a complete response letter, according to a press release.

The FDA also said that PTC Therapeutics would need an additional adequate and well-controlled study to support its next new drug application.

Matthew B. Klein, MD, chief executive officer at PTC Therapeutics, said that the company was disappointed by the FDA’s decision in the press release.

“Friedreich’s ataxia is a rare, physically debilitating, life-shortening, neuromuscular disorder that mainly affects the central nervous system and the heart. Symptoms often appear in the first decade of life,” Klein told Healio.

“There is no cure and no treatment option for children under the age of 16,” he continued. “Loss of ambulation commonly occurs in the second or third decade of life.”

As an investigational oral treatment, Klein said, vatiquinone is a small molecule, first-in-class selective inhibitor of 15-Lipoxygenase (15-LO), which regulates the energetic and oxidative stress pathways disrupted by Friedrich’s ataxia.

By inhibiting 15-LO, vatinquinone helps alleviate the consequences of mitochondrial dysfunction and oxidative stress, which leads to less inflammation and oxidative stress in addition to neuronal survival, PTC Therapeutics said in the press release.

“In clinical studies, vatiquinone has been shown to slow disease progression and improve disease symptoms in Friedrich’s ataxia and other related disorders,” Klein said.

These studies included many that involved pediatric patients, with positive outcomes in mortality as well as in symptoms of neurological and neuromuscular disease, the company said.

Matthew B. Klein

“The global, Phase 3 MOVE-FA clinical trial demonstrated significant (P = 0.021) effect on the most meaningful and only responsive portion of the disease rating scale for the enrolled study population, the majority of whom were under 18 years of age,” Klein said.

The Upright Stability Scale is a key metric of disease progression in ambulatory patients with Friedreich’s ataxia, he added.

“In addition to significant effect on the overall scale, benefit was demonstrated in terms of slowing loss of the ability to perform the key individual items of the scale which have been linked to loss of ambulation,” he said. “Beneficial effect was also shown on the fatigue scale as well as the one-minute walk test.”

Further, long-term data indicated that disease progression slowed by approximately 50% over 3 years relative to natural history, which Klein called a significant difference.

“In addition, the drug has a well-established safety profile, including in young children,” Klein said.

The company said that it believes these data demonstrate vatiquinone’s safety and efficacy for both children and adults living with Friedreich’s ataxia.

Advocacy groups representing patients with Friedreich’s ataxia expressed concern with the FDA’s decision.

“Given the significant unmet medical need in our community, particularly in the youngest population (under 16 years old), we are deeply disappointed by this decision,” Jen Farmer, MS, CEO of the Friedreich’s Ataxia Research Alliance, told Healio.

Andrew Rosen, MBA, MA, CEO of the National Ataxia Foundation, said that his organization was disappointed as well.

“There is only one treatment available currently for Friedreich’s ataxia, and vatiquinone would be the first to treat the pediatric population,” Rosen said. “Ataxia is a complex set of progressive neurological diseases, and it will likely take a number of different therapies to treat all ataxia patients.”

Farmer noted that this rare, genetic neuromuscular disease affects approximately 15,000 children and adults around the world, typically beginning in childhood with difficulties in balance and coordination, followed by lost mobility and energy with life-altering consequences.

Further, Farmer said, the “relentlessly progressive” nature of Friedreich’s ataxia underscores the urgency behind the need to make treatments available as soon as possible, and Rosen agreed.

“We need the FDA to understand that rare diseases cannot be held to the same approval standards of more common conditions,” he said.

Andrew Rosen

FDA regulations allow for broad flexibility in reviewing treatments for rare, life-threatening and severely debilitating diseases, Rosen said.

“We will continue to advocate for those guidelines to be followed,” he said.

Meanwhile, Farmer expressed gratitude to everyone involved in getting research to this point.

“We are grateful to everyone at PTC for their hard work on the trials, data analysis, and regulatory submission as well as the study teams at the clinical sites and the individuals from the Friedreich’s ataxia community who participated in the trials,” Farmer said.

Klein said that PTC Therapeutics will meet with the FDA “as soon as possible” to discuss how it could address the issues described in the complete response letter. Advocacy efforts will persist as well.

“We will continue to work with PTC and the FDA to further understand the basis for the FDA’s decision to inform our future efforts,” Farmer said.

The National Ataxia Foundation will work with other patient advocacy organizations and PTC Therapeutics to determine its next steps, Rosen said, as it continues to represent those affected by ataxia during discussions with the FDA and other stakeholders.

“We will make our voice heard,” he said.

For more information:

Matthew B. Klein, MD, and Jen Farmer, MS, and Andrew Rosen can be reached at neurology@healio.com.