On December 9, the National Eye Hospital (CHNO) Quinze-Vingts in Paris and GenSight Biologics announced that the French National Drug Safety Agency (Agence Nationale de Sécurité du Médicament or ANSM), granted the first Temporary Authorization for Use (ATU) for LUMEVOQ™ (GS010) to treat a patient affected by Leber Hereditary Optic Neuropathy (LHON).
Leber Hereditary Optic Neuropathy (LHON) is a rare, inherited mitochondrial genetic disease, which is caused by a mutation in the mitochondrial DNA (most of the time, the ND4 gene involved in cellular respiration), leading to the degeneration of retinal ganglion cells that results in less than a year, irreversible and definitive vision loss. LHON causes the blindness of an estimated 1,400 to 1,500 new patients each year in the United States and Europe.
Developed by the biopharma GenSight Biologics, the GS010 product candidate, also known as LUMEVOQ™, offered to 37 patients a sustainable functional visual recovery after administration of a single intravitreal product injection to each eye (data reported on May 15, 2019, 96 weeks after injection in the Phase III REVERSE trials). LUMEVOQ™ relies on technology arising from research conducted at the Institut de la Vision in Paris, by associating to the ND4 gene a patented sequence allowing targeting mitochondria. This gene is transferred into the cell using an AAV vector (Adeno-Associated Virus). Then, the ND4 gene is transcribed from DNA to RNA into the nucleus of the cell. Thanks to the patented mitochondrial targeting sequence, the RNA is shuttled into the mitochondria where functional proteins are produced to restore the missing function of the ND4 endogenous gene.
The encouraging results from the REVERSE study allowed Dr. Catherine Vignal, Principal Investigator for LUMEVOQ™ trials at the Department of Ophthalmology at Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts and Head of the department of Neuro-Ophthalmology at the Rothschild Foundation in Paris, to request to the French competent authority, for an ATU to treat a patient affected by LHON. In its press release, GenSight committed to provide the product for a bilateral injection.
France’s ATU program is a powerful means of providing LHON patients with the ND4 mutation, with a therapeutic solution, LUMEVOQ™ gene therapyDr. Catherine Vignal, Principal Investigator for LUMEVOQ™ trials at the Department of Ophthalmology at Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts and Head of the department of Neuro-Ophthalmology at the Rothschild Foundation in Paris,
Actually, In France, the only way to use a pharmaceutical product not yet approved with a Marketing Authorization and not recruiting for a clinical trial requires first obtaining an ATU. This ATU is delivered from the ANSM, under certain conditions: if the product is meant to treat, prevent, or diagnose a severe or rare disease; if the product’s efficacy and safety are presumed in the state of scientific knowledge; and if no other appropriate treatment is available in France. The ATU is requested by and remains under the responsibility of the prescribing physician since the product has the potential to benefit the patient.
As indicated by Pr José-Alain Sahel, Director of the Institut de la Vision; Chairman of the Department of Ophthalmology at Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts; Professor and Chairman of the Department of Ophthalmology at the University of Pittsburgh School of Medicine and the University of Pittsburgh Medical Center; and co-founder of GenSight, this ATU “is the result of a decade of research at the Institut de la Vision and a successful partnership with the teams at GenSight Biologics”. In addition, the “Ouvrir les yeux” (Open the eyes) patient association is also pleased with this authorization, which opens the door to other gene therapies.
As GenSight is preparing to file for Marketing Approval in Europe in 2020 for the LUMEVOQ™, this ATU testifies to the strong therapeutic potential of the product on patients suffering from LHON. In the event that Gensight received this famous Marketing Approval in Europe, LUMEVOQ™ could become the second gene therapy treatment in ophthalmology marketed, after the Luxturna from Spark Therapeutics company indicated in hereditary retinal dystrophy.
Aurélie Laubier, PhD, Project manager DIM Thérapie Génique
GenShight Biologics press release : L’hôpital des Quinze-Vingts et GenSight Biologics annoncent une 1ère Autorisation Temporaire d’Utilisation (ATU) de LUMEVOQ™ (GS010) en France
GenShight Biologics press release : GenSight Biologics annonce les résultats positifs à 96 semaines de l’étude clinique de Phase III REVERSE avec GS010 dans la neuropathie optique héréditaire de Leber (NOHL)