Novartis inks pact with Spark Therapeutics to develop, register & commercialize gene therapy voretigene neparvovec outside US

"No otherwise healthy child should have to go blind due to this devastating disease. Gene therapy is a promising new avenue to potentially address this unmet need," said Shreeram Aradhye, global head of medical affairs and chief medical officer, Novartis Pharmaceuticals. "This collaboration builds on our commitment to ophthalmology. We look forward to leveraging our global presence to ensure that patients outside the US have access to this potentially life-changing treatment."

Novartis will make an upfront payment as well as pay milestones and royalties to Spark Therapeutics reflective of the late stage of the opportunity. Spark Therapeutics retains exclusive rights for Luxturna in the US and will retain responsibility for obtaining EMA approval. Commercialization rights will be transferred to Novartis upon successful completion of registration and issuance of market authorization. Novartis has exclusive rights to pursue development, registration and commercialization in all other countries outside the US. Spark Therapeutics will be responsible for the supply of voretigene neparvovec worldwide under a separate manufacturing and supply agreement with Novartis.

Mutations in the RPE65 gene lead to reduced or absent levels of RPE65 isomerohydrolase activity, blocking the visual cycle and resulting in progressive vision loss and ultimately, blindness. Only a few thousand people worldwide are affected by this ultra-orphan condition. Pending approval, Novartis will work with physicians to establish new approaches to facilitating diagnosis and treatment at specialized treatment centers.

Novartis is a leading ophthalmology company, with therapies that treat both front and back of the eye disorders, including retina diseases, glaucoma, dry eye and other external eye diseases. In 2016, approximately 200 million patients worldwide were treated with Novartis ophthalmic products.

Luxturna is an adeno-associated virus (AAV) vector-based gene therapy indicated in the United States for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy. Patients must have viable retinal cells as determined by the treating physician. Mutations in the RPE65 (retinal pigment epithelial 65 kDa protein) gene lead to reduced or absent levels of RPE65 isomerohydrolase activity, blocking the visual cycle and resulting in impairment of vision. Injection of Luxturna into the subretinal space results in transduction of some retinal pigment epithelial cells with a cDNA encoding normal human RPE65 protein, thus providing the potential to restore the visual cycle.

The safety data reflect exposure to Luxturna in two clinical trials consisting of 41 subjects (81 eyes) with confirmed biallelic RPE65 mutation-associated retinal dystrophy. 40 of the 41 subjects received sequential subretinal injections to each eye. The efficacy in pediatric and adult patients with biallelic RPE65 mutation-associated retinal dystrophy was evaluated in an open-label, two-center, randomized trial. The average age of the 31 randomized subjects was 15 years (range 4 to 44 years), including 64% pediatric subjects (n=20, age from 4 to 17 years) and 36% adults (n=11). The efficacy of Luxturna was established on the basis of multi-luminance mobility testing (MLMT) score change from Baseline to Year 1.

Novartis inks pact, spark therapeutics, therapy voretigene neparvovec outside us