Rare Daily Staff

The Institute for Clinical and Economic Review, an independent non-profit research institute that analyzes the evidence on the effectiveness and value of drugs and other medical services, said its updated Evidence Report assessing the comparative clinical effectiveness and value of Spark Therapeutics gene therapy Luxturna to treat a genetic ultra-rare disease that causes vision loss found its pricing does not meet standard cost-effectiveness thresholds.

The report, issued January 12, was updated after four weeks of public comment.

Earlier this month Spark announced it would charge $850,000 for the one-time therapy, the first gene therapy approved in the United States to treat a genetic disease. At the time, Spark announced three payer programs: an outcomes-based rebate arrangement with a long-term durability measure, a contracting model, and a proposal to CMS under which payments for Luxturna would be made over time. The programs are intended to help ensure eligible U.S. patients have access to Luxturna.

Luxturna is approved for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy that leads to vision loss and may cause complete blindness in certain patients. The condition affects about 1,000 to 2,000 patients in the United States. The RPE65 gene provides instructions for making an enzyme that is essential for normal vision. There are currently no approved pharmacologic treatment options for IRD due to biallelic RPE65 gene mutations.

Luxturna works by delivering a normal copy of the RPE65 gene directly to retinal cells. These retinal cells then produce the normal protein that converts light to an electrical signal in the retina to restore patient’s vision loss. Luxturna uses a naturally occurring adeno-associated virus, which has been modified using recombinant DNA techniques, as a vehicle to deliver the normal human RPE65 gene to the retinal cells to restore vision.

“While the evidence is clear the therapy improves vision for patients over several years, the long-term duration of this benefit remains unknown. Assuming a 10- to 20-year period of benefit, at list price the treatment does not meet standard cost-effectiveness thresholds, even after accounting for the broader societal benefits improved vision has on productivity and education cost,” said David Rind, Chief Medical Officer at ICER.  “The cost-effectiveness findings move into standard ranges only in analyses that consider these non-medical benefits while also assuming that only younger patients with the best baseline vision receive treatment.”

While ICER acknowledge the need to consider contextual factors that could cause treatments for ultra-rare diseases to be priced at levels that exceed traditional cost-effectiveness thresholds, ICER said “policymakers also will need to consider how to manage pricing and payment arrangements for [Luxturna] to ensure long-term affordability, as well as patient access to the coming wave of genetic therapies for other conditions.”

ICER said that assuming a 10- to 20-year benefit of treatment for 15-year-olds – the average age of patients in the clinical trials – economic analyses found that, at the current price of $850,000, use of the treatment would exceed common cost-effectiveness thresholds.

Considering only direct health care system costs, Luxturna would require discounts between 75 percent and 82 percent to align with the benefit to patients treated at age 15, setting ICER’s value-based price benchmark between $153,000 and $217,000.

When also accounting for societal benefits related to education, greater productivity, reduced caregiver burden, and other factors, Luxturna would still require a 50-57 percent discount to remain below these thresholds, ICER said. Even when assuming an as-yet unproven lifetime benefit for the therapy, if found the cost remains well above commonly accepted thresholds.

ICER said separate analyses suggest that Luxturna meets standard cost-effectiveness thresholds when treating only three-year-old patients and accounting for both direct medical costs and broader societal benefits.

Spark said it disagrees with the base-case model that ICER has included in its revised Evidence Report because it continues to exclude the indirect costs associated with vision loss when assessing the cost-effectiveness of Luxturna.

“ICER’s modified societal perspective model more accurately assesses the cost-effectiveness of voretigene neparvovec, as it incorporates the significant indirect costs associated with the disease and non-medical benefits associated with [Luxturna],” Spark said in a statement emailed to Rare Daily. “In both cases, however, ICER’s analysis still fails to account for any benefit of treatment on quality of life for caregivers/family members.”

The ICER report will be the subject of an upcoming public meeting of the Midwest Comparative Effectiveness Public Advisory Council in Kansas City, Missouri on January 25, 2018. The council is one of ICER’s three independent evidence appraisal committees comprising medical evidence experts, practicing clinicians, methodologists, and leaders in patient engagement and advocacy.

Photo: David Rind, chief medical officer of ICER

This story was posted January 17, 2018 and updated January 17, 2018 to incorporate an comment from Spark

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