Expectations for Spark Therapeutics’ Gene Therapy Luxturna in Retinitis Pigmentosa and Leber Congenital Amaurosis


The FDA’s January 2018 regulatory decision deadline on the marketing application for Spark Therapeutics’ gene therapy Luxturna (voretigene neparvovec), for patients with retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA), is being closely watched and eagerly awaited by patients, physicians and industry leaders alike; an EMA ruling on the program will follow later in 2018. Luxturna is a gene therapy that delivers a functional copy of the RPE65, aimed to treat the small subpopulation of RP and LCA patients with mutations in this gene; the program holds orphan drug, breakthrough therapy, and rare pediatric disease designation from the FDA, as well as orphan drug designation from the EMA. If approved, Luxturna would not only be the first pharmacotherapy to launch for RP and LCA, but would also be the first gene therapy to be approved in the United States for any disease—and, thus, a market access pioneer for high-cost, high-impact, single-administration therapeutics.

RP and LCA are areas of high unmet need, which are amenable to gene therapy: RP is an inherited degenerative disorder of the eye that leads to progressive degeneration of retinal photoreceptors, initially presenting as night blindness and tunnel vision, and eventually progressing into blindness. The disease has a complex etiology with mutations in more than 100 genes identified as causative risk factors. LCA is also a retinal degeneration disease with a similar clinical and pathophysiological profile; however, it has an earlier onset (in childhood) and typically progresses faster.

There is no approved pharmacotherapy for either RP or LCA and treatment currently comprises nutritional supplementation and, for some late stage patients, visual prosthetic devices. However, these diseases have become an area of focus for developers of gene therapies, supported by the recent wave of technological advancements made in the field of gene therapy and, more importantly, because of the well-defined genetic underpinnings of inherited retinal disorders, the accessibility of the eye for vector delivery, and the immune-privileged environment of the retina.

Luxturna’s compelling profile will likely support a positive regulatory outcome: Luxturna delivered an impressive performance in a pivotal, 29-patient, open-label Phase III trial; 93% of the treated patients registered a gain in visual function one year after treatment. Furthermore, nearly two-thirds of Luxturna-treated patients in the trial met the multiluminence mobility (MLMT) end point at the lowest light level tested; in contrast, no patient in the control group attained this level of performance. Overall, Luxturna treatment appears to be safe and well-tolerated, although an invasive surgical procedure is required for its subretinal delivery; foveal thinning/reduced visual acuity deemed related to the surgical procedure occurred in one patient. Thought-leading ophthalmologists we interviewed generally have a positive outlook on the likelihood of agent’s approval, projecting ideal use in amenable patients prior to the onset of significant photoreceptor degeneration.

However, Spark must blaze a challenging path to optimize market access and uptake: Although its clinical profile should garner approval for Luxturna, we expect that nonclinical factors including price and formulary coverage will present a challenge for Spark in the lead-in to the product’s launch—especially in the United States, where there is no precedent of a marketed gene therapy. Because Luxturna targets a small percentage of an orphan population, we expect that Spark will seek a high price as compensation for the time, risk, and expenditure associated with the drug’s development; although Novartis (with Kymriah in the U.S. at a price of $475,000 per treatment) and GSK (with Strimvelis in Europe at a price of $709,000 per treatment) have brought comparable clinical breakthroughs to market at lower-than-expected prices, Spark may have a lesser appetite to follow suit as Luxturna will be the company’s only marketed product at launch. As a single-administration, potentially curative therapy, payers would need to absorb the high cost of Luxturna treatment all at once, unless an acceptable risk-based contracting scheme is implemented to distribute the cost over time at level commensurate with clinical performance. However, with the privatized nature of the U.S. health insurance market—which sees patients switch insurers with some regularity—such a payment approach for Luxturna would add logistical burden and risk for Spark.

Although the preservation of vision brings undeniable functional and quality-of-life benefits for amenable patients, Spark must also demonstrate Luxturna’s value to payers. With no approved pharmacotherapies, drug costs associated with the management of RP and LCA are very low, although patients commonly receive multidisciplinary supportive care. As such, Spark will be somewhat more reliant on payers’ willingness to reward innovation and savings on indirect costs with Luxturna, compared with a similar breakthrough in an indication rife with high-cost, chronically-administered products.

Finally, Spark must also work to raise awareness and adoption of genetic testing to maximize the commercial opportunity for Luxturna. The company has launched an initiative to provide free genetic screening for patients with inherited retinal degeneration—ID YOUR IRD—as a step toward the preparation for Luxturna’s launch. The program will ideally identify a pool of Luxturna-eligible patients prior to the product’s launch.

Luxturna will be a transformative therapy for patients and for the healthcare market: Luxturna’s launch will fulfill the unmet need for a curative pharmacotherapy in RP and LCA, albeit for a very small subset of the patient population, and we expect it to provide a life-transforming benefit to a sizeable proportion of the eligible patients over the years. In addition, Luxturna’s launch will also set a benchmark for reimbursement issues surrounding high-cost, single-administration medications with a curative potential, either by persuading payers’ adaptation to support a one-time upfront payment model, or by giving rise to a suitable alternative pricing model. In any case, Spark’s Luxturna will likely be the pioneer gene therapy that will clear the road in the United States, for many other companies with upcoming gene therapies in the pipeline for various genetic disorders.

To learn more about the Retinitis Pigmentosa market, read our Niche & Rare Disease Landscape & Forecast | Retinitis Pigmentosa | US/EU5 content.

In addition, ask about our upcoming Special Report on Gene Therapies, which will examine the clinical and commercial landscape for these next-generation therapeutics for rare diseases.

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