EMA Provides Positive Feedback on Variant’s VAR002 Development Pathway

PARIS, April 3, 2025 /PRNewswire/  Variant and the Rare Ocular Diseases Center at the University of Campania Luigi Vanvitelli (UCLV) today announced positive feedback from the EMA on VAR002, an AAV gene therapy for inherited retinal dystrophies linked to CRX mutations. The EMA’s advice supports VAR002’s non-clinical development plan for a first-in-human trial and confirms that the pivotal toxicology study design will support an EU Marketing Authorisation Application (MAA).  

EMA Scientific Advice: Positive Feedback on VAR002

The EMA provided scientific advice supporting VAR002’s non-clinical development plan. The preclinical program, including toxicology and biodistribution studies, is deemed appropriate for a first-in-human clinical trial. This confirms the adequacy of VAR002’s safety and pharmacological profile for clinical translation. The planned study will assess VAR002 in patients with CRX-associated retinal diseases, addressing a key unmet medical need.  The EMA also confirmed that VAR002’s pivotal toxicology study design meets requirements for a future MAA in the EU. This GLP-compliant study will evaluate VAR002’s safety, biodistribution, and potential toxicity.  The EMA acknowledged the study’s relevance to regulatory expectations for gene therapies, supporting VAR002’s non-clinical development strategy toward clinical trials and market approval.

Securing VAR002’s Development

Variant CEO Denis Cayet stated that EMA emphasized the need to address potential risks of CRX transgene expression outside photoreceptor cells due to hGRK1 promoter autoactivation. These recommendations will strengthen preclinical studies and secure VAR002’s development, ensuring high safety and efficacy for clinical trials.  

About VAR002

VAR002 is a recombinant AAV vector for Leber’s congenital amaurosis, retinitis pigmentosa, and cone-rod dystrophy caused by CRX gene mutations. The therapy delivers a functional CRX gene to replace the defective gene, inducing functional CRX protein expression in photoreceptors. Administered via subretinal injection, VAR002 triggers transgene expression in rods and cones. Recent discoveries show VAR002’s potential beyond CRX-related dystrophies, including diseases with phototransduction pathway defects and ciliopathies. Preclinical studies in animal models, including CEP290-associated ciliopathies, demonstrate its ability to restore retinal function across a broader range of genetic disorders, supporting expanded clinical applications.

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