In 1990, 4-year-old Ashanthi de Silva was born with a severe combined immunodeficiency caused by a lack of adenosine deaminase enzymes [1]. Ashanthi’s parents were horrified over their daughter’s incurable condition and poor prognosis [2]. Fortunately, with the recent discovery of gene alteration, Ashanthi was administered a healthy ADA gene, becoming the first successful gene therapy story in history [1]. For the past decade, gene therapy, which modifies gene expression to treat diseases, has revolutionized the world of medicine [3]. Zolgensma exemplifies a major gene therapy breakthrough in its effective treatment of spinal muscular atrophy (SMA), but its extreme costs and limited accessibility raises the critical question: Is it truly worth it?
SMA is a debilitating autosomal recessive disease frequent in infants and children and characterized by a weakness in voluntary muscles [4]. It is caused by a mutation or absence of the SMN1 gene, leading to a deficiency of the survival motor neuron (SMN) protein responsible for our motor function [5]. Commonly, SMA affects the proximal muscles and can lead to swallowing and breathing complications [5].
In 2019, Zolgensma, also known as onasemnogene abeparvovec-xioi, was approved as the first gene therapy for SMA patients younger than two years old [6]. Requiring only one dose of treatment via an intravenous infusion, Zolgensma replaces the nonfunctioning or missing SMN1 gene with a working SMN gene in motor neuron cells, allowing the body to resume production of SMN proteins [4]. Vectors are transport vehicles for therapeutic genes that use the capsid of a virus whose genes have been removed [7]. The new SMN gene is administered using a nonpathogenic adeno-associated vector 9 that can cross the blood-brain barrier [4].
In the SPR1NT trials, Zolgensma was tested in 15 children with SMA [8]. The results proved that the drug is incredibly effective: 100% of the children achieved independent standing, 93% achieved independent walking, and most development scores were comparable to healthy children [8]. In terms of safety, while each child had at least one treatment-emergent adverse event, most symptoms were moderate without long-term consequences [8].
Today, Zolgensma remains as the only gene therapy available for SMA [5]. Yet, it is priced at an exorbitant $2.1 million, making it one of the most expensive drugs in the world [9]. Some believe this price is economically justified when considering Zolgensma as an orphan drug [10]. Developed for rare medical conditions, orphan drugs entail high per-patient costs due to extensive research expenses and poor profitability from low patient numbers [10]. Despite this justification, few individuals have $2.1 million available to pay upfront, raising the question of accessibility. In an attempt to resolve this issue, a lottery system is held, where 50 free doses of Zolgensma are randomly distributed worldwide over six months [11]. Imagine the devastation of a parent realizing their child’s future rests upon mere chance. By ignoring medical needs, clinical judgements, and structural barriers, a lottery system is nothing but a dehumanizing band-aid to the corrupt business of medicine. Furthermore, by marketing the drug as a one-dose treatment, parents and insurers misinterpret Zolgensma as a miraculous one-time cure [12]. This misconception is dangerous because the efficacy of the gene therapy is contingent upon several factors; not all surviving motor neurons are guaranteed to return to normal SMN protein levels [12].
Choosing Zolgensma over other treatments depends on whether your loved one is younger than two years old and your financial situation. Even with insurance, you are not guaranteed exemption from medical fees, unless you enter Zogensma’s lottery system [13]. Insurance can reduce costs, but the degree to which the burden is alleviated depends on the insurer and the patient’s needs [13]. Nonetheless, Zolgensma is more effective at treating SMA compared to other therapies such as nusinersen and risdiplam. While Zolgensma has a 95% survival rate, risdiplam has an 86% survival rate and nusinersen results in low SMN protein levels in peripheral organs as it cannot cross the mature blood-brain barrier [14]. Zolgensma’s exceptional efficacy outweighs manageable side effects, such as elevated liver enzymes, vomiting, and thrombocytopenia [4]. Zolgensma being a one-time treatment is also convenient, whereas risdiplam requires daily doses and nusinersen requires three doses annually [12,15]. While Zolgensma is considerably more expensive than nusinersen and risdiplam, it remains as the optimal treatment for SMA, if families have the financial means to afford it [16]. Ultimately, Zolgensma is representative of the rising tension in medical innovation, where life-saving scientific advancements collide with our realities of cost and accessibility.
CITATIONS/REFERENCES
[1] The personal side of experimental gene therapy. (n.d.). NIH Clinical Center. Retrieved March 3, 2026, from https://www.cc.nih.gov/news/2016/apr/first-gene-therapy
[2] Ashanthi DeSilva: Revisiting the First Gene Therapy Trial. (2018). Premier Research. https://premier-research.com/perspectives/ashanthi-desilvas-story-a-look-back-at-the-first-gene-therapy-trial/
[3] Gonçalves, G. A. R., & Paiva, R. de M. A. (2017). Gene therapy: Advances, challenges and perspectives. Einstein, 15(3), 369–375. https://doi.org/10.1590/S1679-45082017RB4024
[4] Ogbonmide, T., et al. (2023). Gene Therapy for Spinal Muscular Atrophy (SMA): A Review of Current Challenges and Safety Considerations for Onasemnogene Abeparvovec (Zolgensma). Cureus, 15(3), e36197. https://doi.org/10.7759/cureus.36197
[5] Spinal Muscular Atrophy. (n.d.). National Institute of Neurological Disorders and Stroke. Retrieved March 3, 2026, from https://www.ninds.nih.gov/health-information/disorders/spinal-muscular-atrophy
[6] FDA approves innovative gene therapy to treat pediatric patients with spinal muscular atrophy, a rare disease and leading genetic cause of infant mortality. (2019). U.S. Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-approves-innovative-gene-therapy-treat-pediatric-patients-spinal-muscular-atrophy-rare-disease
[7] Ghosh, S., Brown, A. M., Jenkins, C., & Campbell, K. (2020). Viral Vector Systems for Gene Therapy: A Comprehensive Literature Review of Progress and Biosafety Challenges. Applied Biosafety, 25(1), 7–18. https://doi.org/10.1177/1535676019899502
[8] Strauss, K., et al. (2022). Onasemnogene abeparvovec for presymptomatic infants with three copies of SMN2 at risk for spinal muscular atrophy: The Phase III SPR1NT trial. Nature Medicine, 28, 1390–1397. https://doi.org/10.1038/s41591-022-01867-3
[9] Dean, R., et al. (2021). An updated cost-utility model for onasemnogene abeparvovec (Zolgensma®) in spinal muscular atrophy type 1 patients and comparison with evaluation by the Institute for Clinical and Effectiveness Review (ICER). Journal of Market Access & Health Policy, 9(1). https://doi.org/10.1080/20016689.2021.1889841
[10] Nuijten, M. (2021). Pricing Zolgensma – the world’s most expensive drug. Journal of Market Access & Health Policy, 10(1). https://doi.org/10.1080/20016689.2021.2022353
[11] Dyer, O. (2020). Health ministers condemn Novartis lottery for Zolgensma, the world’s most expensive drug. The BMJ. https://doi.org/10.1136/bmj.m580
[12] Yeo, C. J. J., Simmons, Z., De Vivo, D. C., & Darras, B. T. (2022). Ethical Perspectives on Treatment Options with Spinal Muscular Atrophy Patients. Annals of Neurology, 91(3), 305–316. https://doi.org/10.1002/ana.26299
[13] Brewer, A. (2022). Zolgensma and Cost: How to Find Savings, Lower Cost, and More. Healthline. https://www.healthline.com/health/drugs/zolgensma-cost
[14] Chongmelaxme, B., et al. (2025). Gene-based therapy for the treatment of spinal muscular atrophy types 1 and 2: A systematic review and meta-analysis. Gene Therapy, 32(4), 301–330. https://doi.org/10.1038/s41434-024-00503-8
[15] MacCannell, D., et al. (2022). Restoration of Nusinersen Levels Following Treatment Interruption in People With Spinal Muscular Atrophy: Simulations Based on a Population Pharmacokinetic Model. CNS Drugs, 36(2), 181–190. https://doi.org/10.1007/s40263-022-00899-0
[16] Nusinersen (Spinraza): CADTH Reimbursement Review: Therapeutic area: Spinal Muscular Atrophy [Internet]. (2022). Canadian Agency for Drugs and Technologies in Health. https://www.ncbi.nlm.nih.gov/books/NBK602693/table/tr82698683820713_ch03_t05/
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