European Commission Grants Orphan Drug Designation for Vivet Therapeutics Gene Therapy Product for the Treatment of Cerebrotendinous Xanthomatosis (CTX)

• Pre-clinical data of VTX-806 in mice demonstrated normalization of metabolic parameters in blood and brain, and of upregulated compensatory enzymes
• EUR 4.9 million funding provided by French Government to develop VTX-806 as an effective treatment option to stabilize or reverse symptoms in CTX patients

Paris, France, September 5, 2024 – Vivet Therapeutics (“Vivet”), a clinical stage biotech company developing novel and long-lasting gene therapies for rare inherited liver metabolic disorders, today announces that the European Commission has granted Orphan Drug Designation (ODD) to VTX-806, its gene therapy product for the treatment of CTX, a rare neurodegenerative disease.

Pre-clinical in vivo studies of VTX-806, an Adeno-associated viral (AAV) vector encoding human CYP27A1 for the treatment of CTX, demonstrated a reduction of hepatomegaly in mice, normalization of upregulated compensatory enzymes and of primary and secondary bile acids when compared to current standard of care (SOC) treatments. The submitted data, alongside the chronically debilitating effects of CTX associated leukodystrophies, supported the decision by the EU Commission to grant ODD to VTX-806 as a potential treatment option, bringing significant benefits to patients affected by the burden of CTX in the European Union.

Dr Jean-Philippe Combal, Co-Founder & Chief Executive Officer at Vivet Therapeutics, said: “Early diagnosis and treatment of CTX is crucial to halting disease progression. At present, existing standard of care treatments can only slow or stabilize leukodystrophy, with no cure available. Preclinical data supports VTX-806’s potential as an alternative treatment option to stop, or reverse, disease progression over the long-term, or possibly even cure CTX patients. Receiving ODD from the EU Commission provides Vivet with certain benefits during development and commercialization activities as we press forward with the anticipation of submitting ODD to the US FDA in 2024 and plan to begin preparations to enter clinical development in late 2025.”

VTX-806’s ODD adoption follows the EUR 4.9 million funding Vivet received from the French government to advance the development of the gene therapy for treatment of CTX. The funding covers preclinical research and development activities of VTX-806, including manufacturing process development and a clinical study aimed at identifying neurological biomarkers for the effectiveness of treatment in patients under SOC.

CTX is a rare genetic disorder caused by mutations in the CYP27A1 gene that affects the body’s ability to metabolize cholesterol and bile acids. It is characterized by a buildup of cholestanol in the blood and tissues, which can accumulate in the brain, tendons, eyes, and arteries. This buildup can lead to fatty yellow nodules called xanthomas in the brain’s connective tissues, which can damage the brain and other areas of the body. CTX can present at any age, resulting in chronic diarrhea during infancy, cataracts in late childhood and frequent bone fractures due to brittle bones in children. As a patient enters adulthood, they suffer with progressive leukodystrophy manifesting into dementia, seizures, hallucinations, depression and difficulty with coordination and speech. At present, there is no cure for CTX, only treatment that may stabilize or slow down disease progression.

There are only several hundred identified cases of patients with CTX worldwide¹, due to underdiagnosis, variability of disease presentation (including incomplete penetrance with asymptomatic carriers) and incorrect prediction of pathogenic variants by genetic epidemiology study. Therefore, the exact figure is unknown² but it is estimated that 1000 to 2000 people are affected by CTX in the European Union³ and incidence of 0.1 per million individuals worldwide⁴. These estimates suggest that the actual number of patients with CTX globally is higher than currently reported.

Citations:

¹National Library of Medicines / A blood test for cerebrotendinous xanthomatosis with potential for disease detection in newborns

²National Library of Medicines / Cerebrotendinous Xanthomatosis

³Orphanet Journal of Rare Diseases 18(1):13 / Pramparo T., et al. (2023) ‘Allelic prevalence and geographic distribution of cerebrotendinous xanthomatosis.’

⁴Hunter’s Hope / What is CTX or Cerebrotendinous Xanthomatosis?