Novartis' $2.12M Gene Therapy Zolgensma Approved by FDA for Pediatric Spinal Muscular Atrophy

On May 24, AveXis and Novartis announced that the FDA had approved Zolgensma, the first gene therapy for pediatric spinal muscular atrophy (SMA), for marketing. Novartis acquired this gene therapy by purchasing AveXis for $8.7 billion in April 2018. Zolgensma is indicated for the treatment of patients under two years of age with spinal muscular atrophy (SMA) who have mutations in both copies of the SMN1 gene, which encodes the survival motor neuron (SMN) protein. SMA is a rare genetic disorder that causes progressive muscle weakness and paralysis; if left untreated in severe cases, most patients die by the age of two.

Zolgensma is designed to address the genetic cause of spinal muscular atrophy (SMA) by providing a functional copy of the human SMN gene, thereby halting disease progression through sustained SMN protein expression following a single intravenous infusion. Zolgensma is the first and only FDA-approved gene therapy for the treatment of SMA.

“A diagnosis of SMA is devastating news; without treatment, infants have a very short lifespan, during which they progressively lose the ability to lift their heads, sit up, or roll over, and experience difficulty swallowing and breathing, requiring 24-hour care,” said Dr. Jerry Mendell, Principal Investigator at the Center for Gene Therapy at the Abigail Wexner Research Institute at Nationwide Children’s Hospital in Columbus, Ohio. “In our START clinical trial with Zolgensma, all children were alive at the end of the study, many achieved milestones such as sitting, rolling, crawling, and playing, and some were even able to walk. This therapeutic effect is truly remarkable, offering unprecedented hope for families affected by SMA Type 1.”

Novartis CEO Vas Narasimhan stated, “The approval of Zolgensma demonstrates the efficacy of gene therapy in treating life-threatening genetic disorders, such as spinal muscular atrophy. We believe that Zolgensma can offer a chance of survival for children affected by this rare disease.”

Spinal Muscular Atrophy (SMA) is a rare genetic neuromuscular disorder caused by defects or deletions in the SMN1 gene. In the absence of a functional SMN1 gene, infants with SMA lose motor neurons responsible for muscle function, impairing breathing, swallowing, speech, and ambulation. Without treatment, muscles progressively weaken. In the most severe cases, over 90% of patients experience paralysis and death. SMA is the leading genetic cause of infant mortality. Approximately 450 to 500 infants are born with SMA in the United States each year. Early diagnosis and prompt initiation of treatment, including proactive supportive care, are essential to halt irreversible motor neuron loss and disease progression.

The successful approval and market launch of Zolgensma were based on data from the ongoing Phase 3 STR1VE trial and the completed Phase 1 START trial. These trials evaluated the efficacy and safety of a single intravenous infusion of Zolgensma in patients with Type 1 spinal muscular atrophy (SMA). The data demonstrated that Zolgensma significantly improved patient survival rates. Additionally, Zolgensma treatment led to rapid and sustained improvements in motor function. In the high-dose cohort, CHOP INTEND motor function scores increased rapidly, rising by 9.8 points at one month and by 15.4 points at three months. Furthermore, patients showed varying degrees of improvement in milestones such as independent sitting and standing. In the START trial, patients treated with Zolgensma achieved motor milestones never before attained in the natural history of the disease, including sitting, speaking, and walking, with no waning of effect observed nearly four years after dosing. Safety observations in STR1VE were consistent with those in the START trial; no serious adverse events were reported. The most common adverse reactions were elevated transaminases and vomiting.

What is the price of such an excellent drug capable of providing a one-time curative treatment targeting the root cause? Novartis has set the price at $2.12 million, exceeding RMB 13 million. Biogen’s Spinraza is currently the only approved medication for treating spinal muscular atrophy. Unlike Novartis’s therapy, Spinraza requires lifelong treatment, with a first-year cost of $750,000 and an annual cost of $375,000 thereafter.

Novartis hopes that the external community will understand the value of Zolgensma in this way: the 10-year treatment cost for Spinraza, the existing therapy for spinal muscular atrophy (SMA), is $4.1 million, whereas Zolgensma requires only a single injection, making it nearly 50% cheaper. Meanwhile, Vas Narasimhan stated that they are prepared to offer a five-year installment plan to alleviate the initial financial burden on patients. If the treatment proves ineffective or if the patient dies within the five-year period, Novartis will provide a refund.

For chronic diseases, the current healthcare system is designed around a “pay-as-you-go” model, which is not suited for single-dose therapies capable of achieving complete cures.

Expensive gene therapies are becoming increasingly common. Gene therapy companies such as Novartis and Bluebird Bio have introduced value-based pricing options, whereby the full price is paid only if the drug proves effective or through phased payments over several years. However, the current U.S. Medicaid and Medicare systems are not designed to accommodate these novel solutions, posing challenges for patients undergoing gene therapy.

In an interview with CNBC, Narasimhan stated, “This provides a new paradigm for evaluating the benefits and payment necessity of Zolgensma. We need a new model to determine the value of novel curative therapies relative to the costs and burdens of long-term care.” The pricing of Zolgensma translates to $250,000 per quality-adjusted life year (QALY), which is 50% lower than the pricing threshold for rare genetic disease drugs set by the Institute for Clinical and Economic Review (ICER).

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