On December 19, 2017, the FDA approved Spark Therapeutics’ gene therapy Luxturna for patients with confirmed biallelic RPE65 mutation-associated retinal dystrophies, which include retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA). The FDA decision, which came ahead of the scheduled PDUFA date (January 12, 2018), followed an Advisory Committee panel meeting that voted unanimously in favor of Luxturna’s approval. Luxturna’s launch will not only bring the first pharmacotherapy for RP and LCA patients to the United States, but also heralds a new era of gene therapies in the U.S. healthcare system.

Spark priced Luxturna at $850,000 per patient ($425,000 per eye) in the United States, before discounts.  While various stakeholders are coming to grips with its pharmacoeconomic value, the company is working to establish favorable reimbursement terms for the product, including performance based rebates and reimbursement spread over multiple years, to defray costs.

Separately, Spark and Novartis have recently established a licensing agreement in which Novartis attains exclusive ex-U.S. development and commercialization rights for Luxturna, while Spark retains U.S. rights and the responsibility to secure EMA approval. In return, Spark will receive an upfront payment of $105 million from Novartis, and up to $65 million in additional milestone payments based on near-term European approval and sales in certain markets outside the United States. Moreover, Spark is entitled to future undisclosed royalties on net sales of Luxturna outside the United States.

The agreement may prove to be a highly positive development for RP patients outside the United States. Novartis can leverage its experience with commercializing and marketing Kymriah (a CAR-T gene therapy for ALL) in the United States and Europe, for Luxturna. Moreover, Novartis’s global footprint and its capability, experience, and infrastructure in ophthalmology, combined with Luxturna’s impressive clinical performance, are expected to drive a successful global rollout of the therapy. Such success will likely boost the development of ophthalmological gene therapies, and their worldwide acceptance as a viable treatment.

With Luxturna gaining a foothold and attracting business development interest from a large pharma partner, it’s worth asking “What’s next?” in the RP space. Notably, the RP pipeline comprises numerous additional gene therapies that have the potential to serve larger patients segments than Luxturna. While some of these therapies are genotype-dependent, designed to replace a specific mutated gene, others are genotype-independent, which could in principle serve most or all patients with inherited retinal dystrophies. Such genotype independent approaches include optogenetic strategies or the delivery of a growth factor encoding gene to the retinal cells.

Below, we illustrate the gene therapies in development for RP and LCA and estimate the size of their respective addressable populations. On the graphic, the individual pie “slices” represent the contribution of the various RP subtypes (autosomal dominant; autosomal recessive; X-linked) and the LCA segment to the total population, and the labeled shaded arches represent populations addressable by various gene therapies in clinical or preclinical development. Notably, only a small proportion of RP and LCA patients will be eligible for Luxturna, corresponding to patients with RPE65 mutations (less than 1% of all RP and LCA patients); however, the additional genotype-dependent gene therapies have the potential to serve up to 20% of the RP and LCA patient population, and genotype-independent approaches could see use across the entire population.

Interested to learn more about retinitis pigmentosa and gene therapies? DRG’s Disease Landscape & Forecast (DL&F) module is a comprehensive source of vital disease-specific business and market intelligence. It provides world-class epidemiology, keen insights into current treatment paradigms, in-depth pipeline assessments, and multivariable market forecasts - all supported by detailed primary and secondary research conducted by analysts with deep indication and therapy area expertise.

Access DRG’s in depth analysis of the retinitis pigmentosa market and the clinical and commercial outlook for gene therapies.

Biotech set for good start to 2021

View Now