Spark Therapeutics' blindness gene therapy Luxturna backed by FDA panel

An FDA advisory panel on Thursday voted unanimously in favour of supporting approval for Spark Therapeutics' experimental gene therapy Luxturna (voretigene neparvovec), which is designed to treat patients with vision loss due to confirmed biallelic RPE65-mediated inherited retinal disease. Jefferies analyst Michael Yee has said approval of the therapy would "thematically mark a watershed moment for the entire field." 

According to Spark, the advisory committee's recommendation is based in part on data from a randomised Phase III study involving 29 patients, aged four to 44 years, with confirmed biallelic RPE65 mutations. Results from the study, published earlier this year in The Lancet, showed a significant difference between the Luxturna and control groups at one year on the primary endpoint of mean bilateral multi-luminance mobility testing (MLMT) score change. Moreover, Spark said Luxturna-treated patients achieved a "marked difference" versus controls in regards to the secondary endpoints of full-field light sensitivity threshold (FST) testing averaged over both eyes and the mobility test score change for the first injected eye. However, a third secondary endpoint, the change in visual acuity averaged over both eyes, was not statistically significant between the two groups.

Spark added that on average, participants maintained functional gains seen 30 days after Luxturna administration through to their last annual follow-up visit, as measured by MLMT and FST, with observation ongoing. The company also noted that average improvement in FST testing observed in the Luxturna group at one year was more than 100-fold. Further, no serious adverse events or deleterious immune responses were observed with the therapy.

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Spark indicated that it will not unveil the price for Luxturna until after it receives regulatory approval, although analysts have predicted that the potential one-time gene therapy could cost in excess of $1 million. Still, RBC Capital Markets is forecasting $120 million in Luxturna sales next year, if approved, with some analysts suggesting that despite the anticipated price, the market for the therapy remains small due to the rarity of the disease.

Spark CEO Jeffrey Marrazzo remarked "we are spending a lot of time with payers and policy makers to educate them and eliminate surprises, and we are continuing to explore novel payment and reimbursement models. "However, he cautioned that based on current US price reporting regulations, Spark would suffer a "financial penalty on government business if we offered a pay-for-performance model to commercial plans," adding that the company is "engaging frequently in [Washington DC]" to attempt to find a way to overcome the issue.

Institute for Clinical and Economic Review chief medical officer David Rind said gene therapy is "likely to end up truly curing some horrific diseases and we're going to have to figure this stuff out…how we pay for it, how we assess it, what fair pricing is." Meanwhile, Wedbush Securities analyst David Nierengarten commented that regardless of what pricing model Spark selects, Luxturna "will be a precedent setter."

The FDA is expected to issue a decision regarding whether to approve Luxturna by January 12, 2018. The gene therapy has also been submitted for approval in Europe. 

In August, the FDA cleared Novartis' CAR-T cell therapy Kymriah (tisagenlecleucel) for use in certain paediatric and young adult patients with acute lymphoblastic leukaemia, marking the first approval of a gene therapy in the US. Novartis said at the time that a one-time single administration treatment with Kymriah would cost $475 000, but that it was working with the US Centers for Medicare and Medicaid Services on an outcomes-based approach that would allow for payment only when patients respond to the therapy by the end of the first month.

For related analysis, see ViewPoints: Briefing docs presage landfall of first gene therapy for monogenic disease in US. See also ViewPoints: Spark sets the stage for new drug pricing debate with gene therapy review.

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