[Editor’s note: This is the fourth in a series of articles on Zolgensma and treatments for SMA, the issues they raise, and possible discoveries to come, all drawn from recent interviews with neurologists and researchers involved in this work. Others in this series can be found here.
SMA News Today is also interested in speaking with families of children treated with Zolgensma in its approved form, using intravenous injection, to share their experiences and opinions with our readers. If you or those you know are open to this interview, please contact us at [email protected]]
Although it carries a substantial price tag, Zolgensma (onasemnogene abeparvovec-xioi) could be cost-effective for spinal muscular atrophy (SMA) patients over time, and its approval is likely to leap-frog work on gene therapies for this and other diseases, say neurologists and researchers.
The first gene therapy approved to treat SMA, it comes at a hefty cost of $2.125 million upfront, or $425,000 per year under a five-year installment plan.
This makes Zolgensma the world’s most expensive medicine by list price. But Novartis — the company marketing and now leading its development with AveXis, which it acquired in 2018 — has said that it took a “responsible approach” to pricing.
Spinraza (nusinersen, by Biogen), the first approved SMA therapy, costs $750,000 for its first year of use and $375,000 for subsequent years, roughly reaching Zolgensma’s list price after five years of use and nearly $4.1 million at 10 years.
“You can see where [Zolgensma’s] price comes from,” Arthur Burghes, PhD, a researcher at The Ohio State University College of Medicine, said in an interview with SMA News Today. “Obviously, it lasts longer than five years … [and] it’s approximately 50% cheaper than Spinraza over 10 years.”
Similarly, the gene therapy is about 50% less expensive overall than 10-year costs of treating genetic pediatric ultra-rare diseases, Novartis reported shortly after approval was announced May 24.
“I think it can be justified … treatment can cost that much, a one-time treatment,” said Jerry Mendell, MD. “The clinical trials alone has cost us [Nationwide Children’s] close to $10 million.” Mendell, an attending neurologist at Nationwide Children’s Hospital and principal investigator for the hospital’s Center for Gene Therapy, led the gene therapy’s pivotal study and is continuing to lead its long-term extension.
“This is expensive treatment, it’s expensive therapy,” he said, adding that he believes insurance companies, supported by federal or nonprofit programs, will come to cover Zolgensma. “I think we’ll have to grow accustomed to this [price] as new forms of gene therapy are introduced.”
The cost of not treating a chronic and severe disease like SMA — which leaves babies with type 1 unable to eat or breathe on their own, and robs older children with types 2 or 3 of the ability to use their arms or legs in ways others take for granted — also weigh on determining a valid price, said Vincent Carson, MD, a pediatric neurologist with the Clinic for Special Children in Pennsylvania, and others interviewed.
“In the end, Zolgensma might actually be more affordable than paying for SMA over a lifetime,” Carson said, noting that drug development is now thought to cost between $500 million and $1 billion. “For companies to invest all this … they need to somehow get that money back at the very least.”
Zolgensma might also be a one-time therapy for those caught early in the disease’s course, newborns and pre-symptomatic infants.
“The whole costing structure is going to be completely different in this kind of treatment because you’re giving it once and it’s done,” Burghes said. “You’re not having a continual income source.”
A competitive treatment field for SMA …
Burghes favored a more expansive treatment field, one with greater options for patients and the competition that might affect prices.
“Let’s have the third competitor into the field — which could be the Roche drug compound [risdiplam] — and see if it can drop down even more,” Burghes said. He particularly liked the potential that risdiplam, which is still in testing, might offer as an oral treatment that “can be relatively easily administered to adults with SMA.”
Gene therapy “is likely to fit mostly into the treatment options early, and I’m talking about symptomatic cases as well as newborn screening,” he added. Whether babies given Zolgensma might need an additional disease-targeting treatment as they age — like Spinraza or possibly risdiplam — is still to be determined.
Carson is “optimistic that the [pharmaceutical] companies will be eager to help all the children that they can,” putting in place assistance programs for those who need treatment but cannot afford it.
Still, along with other experts interviewed, he favors all parties — from insurance companies to government, pharma companies to patient associations — coming together to “look at the way we’re doing things, and think about this in a new way.”
… and possibilities for other diseases
Zolgensma’s approval not only marked a first gene therapy for SMA, but also for any genetic disorder of the central nervous system, an impact that did not go unnoticed.
“It’s wonderful. This is a revolutionary medicine,” said Carson, a co-investigator in the Phase 3 SPR1NT trial of Zolgensma (NCT03505099), which is currently recruiting, in presymptomatic newborns. “I’m hopeful that in the next 10 to 20 years … we will have treatments for children with a range of neurologic disorders.”
In a prior interview, Mendell underscored exactly how “revolutionary” work that led to Zolgensma has been — clearing a path to effective, high-dose studies of gene therapies such as the Phase 1/2 trial in Duchenne muscular dystrophy that he is also leading. In this study (NCT03375164) of a microdystrophin gene therapy in children, the dose under evaluation is the same as Zolgensma’s, “the highest dose of virus that had ever been given in a clinical trial,” he said.
“The SMA approval … shows the potential unequivocally. We’re optimistic about the Duchenne patients and other forms of muscular dystrophy we’re working on as well,” he added in the recent talk.
Mendell, a clinical translational scientist — who works to “translate” lab research into treatments and has been involved in gene therapy research for more than 15 years — also looks to broader possibilities.
“This is [a] systemic gene therapy, and we established safety and efficacy,” he said. “It will be applied to other diseases as well.”
Both a high viral dose “so that you’ll hit the maximum number of cells possible” and “giving it early so you’ve limited any damage” are key to its working across diseases, Burghes said. Gaucher, Pompe, and Batten are all lysosomal storage disorders — metabolic diseases characterized by a buildup of toxic materials in the cells — he sees as targeted for treatment with gene therapies.
With Gaucher, specifically, the AAV9 viral subtype used as a transport agent for Zolgensma could factor in treating the disease’s impact on the nervous system, Burghes said. A bone marrow transplant would address the disease’s peripheral — systemic — damage.
This study includes intrathecal (spinal cord) administration in children ages 2–5 with type 2 SMA, with the FDA-approved intravenous route reserved for infants. Intrathecal administration is more targeted, meaning it “can reduce the dose and can actually more specifically treat the nervous system,” Burghes said, making it safer for older patients most likely to develop antibodies to Zolgensma’s viral vector.
“I could see many applications where this could have significant impact” if study results support spinal cord delivery, he said.
John Brandsema, MD, a pediatric neurologist with Children’s Hospital of Philadelphia, added: “What we hope for is to impact as many of our diseases as possible in a positive way, and realize a different way of living with these diseases in the lifetimes of our current patients.”
But as the field advances, he added, all involved need “to make sure we do it in a way that’s highly regulated and both safe and efficacious for patients — we want to do this in an optimal way.”
That’s also important because a grand goal awaits. “About a month ago, I received an award from the American Brain Foundation that I think summed up in better words than I can say,” Mendell concluded. “And that’s: Cure One, Cure Many.
“I think that’s really what we’re looking at.”