The Institute for Clinical and Economic Review has found that a new gene therapy from Novartis AG is more cost-effective than Biogen Inc.'s Spinraza in treating a rare, debilitating infant disease called spinal muscular atrophy.
A Dec. 20 draft report from the U.S. drug pricing watchdog assessed the value of the two therapies, determining that the current standard of care is less cost-effective than the newer therapy.
Spinraza is the only marketed treatment that targets the survival motor neuron gene and induces it to create more of a needed protein that is deficient in patients with spinal muscular atrophy. It was approved in December 2016 by the U.S. Food and Drug Administration to treat most types of the disease.
The experimental gene therapy called Zolgensma from AveXis Inc., which was acquired by Switzerland-based Novartis in April, employs a modified virus to deliver a copy of the survival motor neuron gene to replace the defective one, a one-time treatment. The therapy was granted FDA priority review in early December.
Due to the nature of the disease, the most common type of which affects infants and is generally fatal before the age of 2, long-term data remains unavailable for both treatments. For this reason, the institute's U.K. counterpart, the National Institute for Health and Care Excellence, did not recommend Spinraza for coverage under the country's National Health Service.
The Institute for Clinical and Economic Review, or ICER, uses a measurement for cost-effectiveness known as quality-adjusted life years, or QALYs, a mathematical determination of a drug's effectiveness in prolonging a patient's life and improving quality of that life versus the drug's cost per year.
For Spinraza, ICER estimated a cost of $728,000 per QALY, well above the normal threshold of $50,000 to $150,000 the nonprofit organization uses as a benchmark. The group also pointed out that Spinraza is most effective in patients who have not yet shown symptoms of the disease or whose disease is in early stages.
ICER found that Zolgensma would potentially cost $247,000 per QALY and is a one-time therapy. The watchdog's price for the drug is based on a placeholder value of $2 million, as the therapy is not currently approved. The therapy has only completed tests in patients with Type I spinal muscular atrophy, the most common subtype.
The draft report is open for public comment until the end of January, and ICER plans to publish an evidence report in February.
High cost of care
Without treatment, spinal muscular dystrophy requires around-the-clock care as the disease can result in a complete loss of motor neurons by six months of age, AveXis President Dave Lennon said on a call prior to ICER's release of the report.
"90% of babies who are born with Type I need either permanent breathing support or succumb to their disease by their second birthday," Lennon said. "So you see a rapid progression of disease in these patients up to and including death very quickly."
Beyond the two drugs, the only option for patients with the disease is supportive care, involving various elements of life support, including ventilators or feeding tubes — therapies that come at a high cost.
"Best supportive care is not really a great outcome for patients and leads to permanent disability and a lifetime of monitoring and support from the caregiver," Lennon said.
Because of the debilitating nature of spinal muscular dystrophy, AveXis questioned ICER's normal protocol, suggesting two major changes to the evaluation process for the gene therapy.
AveXis Global Head of Medical Affairs Ramin Farhood said comparing the gene therapy to the standard of care, because of the vast differences in results, can artificially skew the cost-effectiveness. He also said ICER should consider employing a threshold of $500,000 per QALY, much higher than usual, because of the nature of the one-time treatment and the rarity of the disease.
"This is an established and appropriate cost-effectiveness benchmark for really small populations," Farhood said. "Part of it is because it is a significant medical, economic and emotional burden on patients, families and caregivers, as well."
Lennon said that gene therapy, being so new, is a difficult and unexplored area of medicine in terms of value.
"We're really entering an unprecedented period with the introduction of gene therapies," Lennon said. "There isn't a whole lot of precedent yet for how these products should be evaluated. There's a lot of uncertainty regarding inclusion of different elements of value that may be important as we consider gene therapies ultimately as potential cures for the diseases that they treat, and that's currently not part of standard cost-effectiveness methods."
The health system is not designed for the entry of a one-time therapy, he said.
"Our healthcare system today is really structured to treat diseases chronically," Lennon said. "We have to think differently about how we value these medicines and think differently about how we pay for them."