FDA Tells PTC It Will Not Approve Its FA Drug

Rare Daily Staff

The U.S. Food and Drug Administration told PTC Therapeutics that it will not approve its application to market vatiquinone for the rare, neurodegenerative disorder Friedreich’s ataxia.

The FDA notified the company that substantial evidence of efficacy was not demonstrated for vatiquinone, and that an additional adequate, well-controlled study would be needed to support resubmission of its application.

Friedreich’s ataxia (FA) is a rare, physically debilitating, life-shortening neuromuscular disorder that mainly affects the central nervous system and the heart. It is the most common hereditary ataxia—abnormal, uncoordinated movements—caused most often by a single genetic defect in the frataxin gene, which leads to reduced production of frataxin. This mitochondrial protein is crucial for cellular metabolism and energy production. Decreased frataxin levels are associated with mitochondrial iron accumulation and increased oxidative stress, which can lead to cell death through ferroptosis.

Symptoms include progressive loss of coordination and muscle strength, leading to poor balance and coordination; difficulty speaking, swallowing, and breathing; curvature of the spine; serious heart conditions; diabetes; and hearing and vision impairment. The severity of symptoms and speed of progression vary between people, and some symptoms may not be evident in all patients. Friedreich’s ataxia is usually diagnosed in childhood or adolescence.

Vatiquinone is a small molecule, first-in-class selective inhibitor of 15-Lipoxygenase—an enzyme that is a key regulator of the energetic and oxidative stress pathways disrupted in Friedreich’s ataxia. Inhibiting 15-LO helps alleviate the consequences of mitochondrial dysfunction and oxidative stress, ultimately decreasing inflammation, reducing oxidative stress, and promoting neuronal survival. Vatiquinone has been evaluated in numerous clinical studies, many focused on pediatric patients, and has demonstrated an impact on mortality risk and a range of neurological and neuromuscular disease symptoms.

“We believe the data collected to date demonstrate that vatiquinone could provide a safe and effective therapy for both children and adults living with Friedreich’s ataxia,” said Matthew Klein, CEO of PTC Therapeutics. “We plan to meet with the FDA to discuss potential steps to address the issues raised in the [complete response letter].”

Photo: Matthew Klein, CEO of PTC Therapeutics