VARIANT Receives Positive Feedback from the European Medicines Agency (EMA) for its Innovative Gene Replacement Therapy, VAR002

PARIS, April 3, 2025 /PRNewswire/ -- Variant, a company dedicated to developing innovative treatments for orphan inherited eye diseases, and the Rare Ocular Diseases Center at the University of Campania Luigi Vanvitelli (UCLV) in Naples today announced that they have received positive feedback from the European Medicines Agency (EMA) on VAR002, an adeno-associated viral vector gene therapy targeting inherited retinal dystrophies linked to CRX mutations. This consultation and subsequent feedback from the EMA ensure that the non-clinical development plan of VAR002 is suitable for a future first-in-human clinical trial. It also confirmed that the planned pivotal toxicology study design will support a Marketing Authorisation Application in the EU.

EMA Scientific Advice : Positive Feedback on VAR002

The European Medicines Agency (EMA) provided scientific advice supporting the non-clinical development plan of VAR002, an adeno-associated viral vector gene therapy targeting inherited retinal dystrophies linked to CRX mutations. The preclinical program, including pivotal toxicology and biodistribution studies, was deemed appropriate to advance towards a first-in-human clinical trial. This endorsement confirms that the data generated so far adequately supports the safety and pharmacological profile of VAR002, ensuring a solid foundation for clinical translation.

The planned study will assess VAR002 in patients with CRX-associated retinal diseases, addressing a critical unmet medical need in ophthalmic gene therapy.

The EMA also confirmed that the planned pivotal toxicology study design for VAR002 aligns with the requirements to support a future Marketing Authorisation Application (MAA) in the EU. The study, conducted in compliance with Good Laboratory Practice (GLP), will assess the safety, biodistribution, and potential toxicity of VAR002, ensuring a comprehensive evaluation of its risk-benefit profile.

The EMA acknowledged the study's relevance in addressing key regulatory expectations for gene therapies, reinforcing the robustness of VAR002's non-clinical development strategy as it advances towards clinical trials and eventual market approval.

Securing the Development Pathway for VAR002

"The EMA has highlighted the need for particular attention to the potential risks associated with CRX transgene expression outside of photoreceptor cells due to autoactivation of the hGRK1 promoter" says Denis Cayet, CEO of Variant. "These recommendations are instrumental in strengthening the robustness of our preclinical studies and, ultimately, securing the development pathway for VAR002, ensuring the highest safety and efficacy standards as we progress toward clinical trials."

ABOUT VAR002
VAR002 is a recombinant adeno-associated viral (rAAV) vector initially developed to treat Leber's congenital amaurosis, Retinitis pigmentosa, and Cone-rod dystrophy due to a mutation in the CRX gene. This gene replacement therapy provides an unmutated copy of the human CRX gene to replace the defective gene, inducing the expression of a functional CRX protein in the photoreceptors. VAR002 is administered as a sterile suspension of viral particles, injected directly into the subretinal space. This triggers the expression of the transgene in the rods and the cones. Recent discoveries have further demonstrated the potential of VAR002 beyond CRX-related inherited retinal dystrophies, particularly in diseases associated with defects in phototransduction pathways and ciliopathies. Preclinical studies in relevant animal models, including CEP290-associated ciliopathies, have highlighted its capacity to restore retinal function in a broader range of genetic disorders, paving the way for expanded clinical applications.

ABOUT VARIANT
Variant is a biotechnology company dedicated to developing innovative gene therapy solutions for inherited retinal diseases. Variant focuses on leveraging retinal transcription factors to restore photoreceptor function in severe retinal dystrophies. Variant has initiated a Translational Preclinical Task Team, working alongside Professor Francesca Simonelli (Naples Hospital, Italy), to accelerate the transition from research to clinical application. 

ABOUT The Centre for Rare Ocular Diseases Center at University of Campania Luigi Vanvitelli, Naples, Italy.
The Centre for Rare Ocular Diseases of the academic hospital University of Campania Luigi Vanvitelli offers diagnostic, rehabilitative and therapeutic courses for patients suffering from hereditary eye diseases. Recently, a "Telethon Advanced Ocular Therapy Unit" was created at the Centre, unique in Italy and among the few in Europe, dedicated to clinical studies aimed to evaluate innovative therapeutic strategies for the treatment of rare ocular diseases. This way, patients can be enrolled in major clinical studies for hereditary eye diseases. 

CONTACT:                                                                                                                                       
Dorothée M.
+33 9 53 73 68 15
[email protected]

SOURCE Variant