RARE Daily

PTC’s Candidate Fails in Late-Stage Trial in Friedreich Ataxia, Discontinues Early Gene Therapy Programs

May 24, 2023

Rare Daily Staff

PTC Therapeutics reported topline results from the MOVE-FA trial of vatiquinone in patients with Friedreich ataxia that failed to meet its primary endpoint of statistically significant change in mFARS score at 72 weeks in the primary analysis population.

However, vatiquinone treatment did demonstrate significant benefit on key disease subscales and secondary endpoints. In addition, in the population of subjects that completed the study protocol, significance was reached in the mFARS endpoint and several secondary endpoints.

“While we are disappointed that the study did not achieve its primary endpoint, we are encouraged by the findings of meaningful impact on several different aspects of FA disease progression and morbidity over 72 weeks,” said Matthew Klein, CEO, PTC Therapeutics. “Given the signals of clinical benefit, vatiquinone’s well-established safety profile in children, and the unmet medical need for pediatric patients with FA, we look forward to discussing a potential path to registration with regulatory authorities.”

Friedreich 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) and is usually caused by a single genetic defect in the frataxin (FXN) gene that leads to reduced production of frataxin, a mitochondrial protein that is important 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 varies between people and some symptoms may not be evident in all. Friedreich ataxia is usually diagnosed in childhood or adolescence. Approximately 25,000 people have Friedreich ataxia globally.

Vatiquinone is a small molecule, first-in-class selective inhibitor of 15-Lipoxygenase (15-LO), an enzyme that is a key regulator of the energetic and oxidative stress pathways that are disrupted in Friedreich ataxia. Inhibition of 15-LO helps to alleviate the consequences of mitochondrial dysfunction and oxidative stress, ultimately preventing ferroptosis and aiding neuronal survival. Vatiquinone has been evaluated in a number of clinical studies and has demonstrated an impact on mortality risk and a number of neurological and neuromuscular disease symptoms.

While PTC thinks the data justify moving ahead with the drug, at the same time it said it will discontinue preclinical and early research programs in gene therapy as part of a strategic portfolio prioritization, which includes an 8 percent reduction in the workforce. PTC will continue its development and global commercialization of Upstaza, the first-ever approved gene therapy directly administered to the brain. As a result of the prioritization, estimated reductions of approximately fifteen percent in residual 2023 operating expenses are expected. In addition, PTC Therapeutics also said that PTC’s Chief Financial Officer Emily Hill has been relieved of her responsibilities and will be leaving the organization.

The discontinued gene therapy programs include preclinical stage programs in Friedreich ataxia and Angelman syndrome as well as several other programs targeting rare CNS and ophthalmological disorders of high unmet medical need at various stages of preclinical development. The prioritization decision will allow for additional focus on PTC’s proprietary splicing platform as well as additional CNS and metabolic disorders that leverage its differentiated and innovative scientific expertise.

“We are incredibly proud of PTC’s accomplishments in the field of gene therapy, including the pioneering work associated with the approval of Upstaza. We believe that the decision to discontinue our pipeline gene therapy programs enables PTC to focus R&D efforts on our other innovative and differentiated scientific platforms and strongly positions us for long-term growth and success,” Klein said. “Where possible, we will work to ensure that the discontinued gene therapy programs can be developed by other parties so that the therapies have the potential to benefit patients.”

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