Delving into the Latest Updates on Onasemnogene abeparvovec with Synapse

Overview

Basic Info

Drug Type

AAV based gene therapy

Synonyms

ChariSMA, OAV101 IT, onasemno-gene abepar-vovec

+ [15]

Target

SMN1

Action

stimulants

Mechanism

SMN1 gene stimulants(survival of motor neuron 1, telomeric gene stimulants)

Therapeutic Areas

Nervous System DiseasesOther Diseases

Active Indication

Spinal Muscular AtrophyMuscular Atrophy, Spinal, Type II

Inactive Indication

HMN (Hereditary Motor Neuropathy) Proximal Type IJuvenile Spinal Muscular Atrophy

Originator Organization

Novartis Gene Therapies, Inc.

Novartis Pharma AG

Active Organization

Novartis Pharma AGChina Novartis Institutes for BioMedical Research Co., Ltd.

Novartis Pharmaceuticals Corp.

+ [4]

Inactive Organization

Novartis Gene Therapies, Inc.

Beijing Novartis Pharma Co., Ltd.Novartis Pharma Schweiz AG

License Organization

Novartis Gene Therapies, Inc.

RegenxBio, Inc.

Healthcare Partners

Drug Highest PhaseApproved

First Approval Date

United States (24 May 2019),

Spinal Muscular Atrophy

RegulationOrphan Drug (United States), Priority Review (China), Breakthrough Therapy (China), Orphan Drug (South Korea), Orphan Drug (Australia)

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Structure/Sequence

Sequence Code 246508004

Source: *****

Spinal muscular atrophy (SMA) is a rare neuromuscular disorder and an important genetic cause of infant mortality. Universal newborn screening (NBS) enables presymptomatic disease-modifying therapy (DMT) but increases upfront costs. This study evaluated the cost-effectiveness of universal SMA NBS in Taiwan.

METHODS:

This study built a state-transition simulation model for a hypothetical SMA birth cohort using local epidemiology and costs and published clinical inputs. Strategies were as follows: (1) NBS with presymptomatic DMTs and (2) clinical identification (CI) with symptomatic DMTs. DMTs included nusinersen, onasemnogene abeparvovec, and risdiplam (reimbursed by Taiwan's National Health Insurance). Incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated over 10-year and lifetime (90-year) horizons from Taiwan's payer and societal perspectives. The willingness-to-pay (WTP) threshold was 3 times Taiwan's 2022 GDP per capita (New Taiwan Dollar (NTD) 2 917 650/QALY). One-way, probabilistic sensitivity, and scenario analyses assessed uncertainty.

RESULTS:

All ICERs were below WTP threshold. From the payer perspective, ICERs for NBS with presymptomatic DMT versus CI with symptomatic DMT were NTD 1 157 970 (USD 38 599) /QALY (10 years) and NTD 2 108 499 (USD 70 283)/QALY (lifetime). From the societal perspective, ICERs were NTD 261 789 (USD 8726)/QALY (10 years) and NTD 1 494 002 (USD 49 800)/QALY (lifetime). Results were most sensitive to DMT costs (particularly nusinersen and risdiplam) and health-state utility values.

CONCLUSIONS:

Universal SMA NBS with presymptomatic DMT is likely cost-effective in Taiwan from both payer and societal perspectives under the WTP threshold, supporting earlier treatment to slow progression and improve quality of life.

01 Nov 2026·ADVANCES IN THERAPY

Longitudinal Dosing Patterns and Treatment Costs Among Patients with Spinal Muscular Atrophy Initiating Nusinersen and Risdiplam

Article

Author: Song, Wei ; Ye, Dongni ; Yang, Min ; Toro Jimenez, Walter ; Lemus Wirtz, Esteban

INTRODUCTION:

Spinal muscular atrophy (SMA) is a neuromuscular disorder historically associated with high morbidity, mortality, and healthcare costs. Disease-modifying therapies have improved outcomes, but their long-term economic burden remains uncertain. Nusinersen and risdiplam, both chronic therapies, differ from onasemnogene abeparvovec, a one-time gene therapy. Understanding real-world treatment costs of chronic SMA therapies is critical to inform therapeutic choice.

METHODS:

This retrospective cohort study used the Komodo Health Research Database (2016-2024). Patients with SMA aged ≥ 2 years who initiated nusinersen or risdiplam were followed up to 5 years. Dosing patterns and drug acquisition and administration costs (2024 USD) were assessed annually, overall and by age group and scoliosis status.

RESULTS:

Among 3864 eligible patients, 2743 initiated nusinersen and 1121 initiated risdiplam (mean age 21.4 vs. 25.3 years, respectively; 51.5% vs. 46.1% male). Median follow-up was 5.5 years for nusinersen and 1.1 years for risdiplam. Persistence declined over time, with 39.5% of patients treated with nusinersen and 63.7% of patients treated with risdiplam remaining on their index therapy at years 5 and 4. Patients treated with nusinersen received 3.6 injections on average in year 1 and 2.8-3.1 annually thereafter. Median annualized nusinersen treatment costs were $504,173 in year 1 and $438,788-548,608 in years 2-5. Patients treated with risdiplam had a median of 96 days of supply in year 1 (51.5% with > 90 days); median annualized drug costs were $143,331 overall in year 1 and $259,419 among those with > 90 days of supply, increasing to $264,701-289,340 in years 2-4. Costs were similar across subgroups.

CONCLUSION:

Nusinersen and risdiplam persistence declined over time. Among patients remaining on their index therapy, both treatments had high long-term costs, highlighting the substantial and ongoing financial burden of chronic SMA therapies and the need for real-world evidence to inform healthcare planning.

TRIAL REGISTRATION:

ClinicalTrials.gov identifier, NCT07378943.

01 Nov 2026·Journal of Neuromuscular Diseases

Determinants of hepatic enzyme elevations following onasemnogene abeparvovec: Results from a unified immunomodulation protocol

Article

Author: Dhawan, Anil ; Mundada, Vivek ; Parashar, Syon

Introduction:

Onasemnogene abeparvovec is an adeno-associated virus serotype 9 (AAV9) gene therapy for spinal muscular atrophy (SMA) that is frequently associated with immune-mediated hepatotoxicity. Previous studies have suggested that older age and higher body weight may increase the risk or severity of hepatic enzyme elevation; however, interpretation is limited by heterogeneous immunosuppression strategies across centers.

Method:

We conducted a retrospective cohort study of children with SMA who received onasemnogene abeparvovec between 2020 and 2025 and were managed using a unified, protocol-driven immunomodulation strategy. Peak alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values (upper limit of normal [ULN] 35 U/L), as well as the timing of peak transaminase elevations, were analyzed in relation to age and weight at infusion.

Results:

Among 152 children with adequate biochemical follow-up, hepatic enzyme elevation was common: 63.2% had peak ALT ≥2× ULN and 29.6% had peak ALT ≥5× ULN. Weight demonstrated a statistically significant but modest correlation with peak ALT magnitude (r = 0.184, p = 0.023), whereas age was not associated with transaminase severity. In contrast, age correlated with delayed timing of peak ALT (r = 0.229, p = 0.005) and AST (r = 0.283, p < 0.001). All hepatic enzyme abnormalities resolved under protocol-based immunomodulation, and no cases of hepatic failure or synthetic dysfunction occurred.

Conclusion:

When managed with a structured, proactive immunomodulation protocol, hepatotoxicity following onasemnogene abeparvovec is predictable and manageable. Weight modestly influences ALT severity, while age primarily affects the timing rather than the magnitude of hepatic immune activation, supporting safe administration across a broad pediatric age and weight spectrum.

488

News (Medical) associated with Onasemnogene abeparvovec

11 Nov 2026

·www.biospace.com

Novartis’ Zolgensma woes, BIO’s China plan, GLP-1s’ new safety warning, FDA’s stacked November

Novartis confirms that nine patients treated with its spinal muscular atrophy gene therapy Zolgensma have developed tumors; the FDA orders GLP-1 drugmakers to add a warning to their labels about the risk of a rare eye condition that can lead to vision loss; and the agency is set to decide on no fewer than 11 therapies this month, including closely watched applications from Summit Therapeutics, Vertex and Capricor Therapeutics. > Listen on Spotify > Listen on Apple Products > Listen on Amazon Music > Listen on iHeart > Watch on YouTube This biggest news of the past week was undoubtedly the revelation of tumors developing in patients with spinal muscular atrophy who received Novartis’ Zolgensma. The FDA has now launched an investigation into the approved gene therapy. Then, to add insult to injury, the Swiss pharma revealed detailed results from its failed HORIZON cardiovascular trial , and no matter which way the data were cut, the results remained negative. Novartis and partner Ionis revealed in September that pelacarsen, which lowers levels of lipoprotein(a), failed to show efficacy in lowering the risk of major adverse cardiovascular events. With the new data offering “little silver lining,” according to Truist Securities, Lp(a) as a target in cardiovascular disease is being further scrutinized. On a global scale, China has been on the rise when it comes to biotech, as evidenced by the volume of licensing deals going to Chinese companies. The Asian country has been working toward this goal for a long time, with the government releasing carefully curated strategic plans every five years for the past few decades. Now, the Biotechnology Innovation Organization (BIO) has released a proposal laying out seven policies the U.S. government can work on to help protect the American biotech industry. In the weight loss space, the FDA is requiring a label update for all 12 GLP-1 receptor agonists currently on the market to now include a potential increased risk for a rare eye disease that causes optic nerve swelling and can lead to blindness. Cases of the disease have been reported for all currently marketed GLP-1s, according to the FDA, including Novo’s semaglutide drugs Wegovy and Ozempic and Eli Lilly’s tirzepatide franchise, Zepbound and Mounjaro, as well as its oral GLP-1, Foundayo. On the oral front, frontrunners Novo and Lilly have been duking it out for market share. In its third quarter earnings call last week, Novo said Lilly’s claim that Foundayo is closing on in the Wegovy pill isn’t quite right. Meanwhile, Lilly released results from a Phase 3 sleep apnea trial of Foundayo—upon which the company will seek its second approval in the indication; Lilly’s first sleep apnea approval—and the first overall for the condition—was for its injectable Zepbound in 2024. Meanwhile, Zealand and Boehringer Ingelheim are one step closer to global regulatory filings for their dual glucagon and GLP-1 receptor agonist survodutide after a late-stage trial showed the drug did not raise the risk of cardiovascular death. The FDA has a full docket this month, including pending decisions for Summit Therapeutics and Akeso’s bispecific antibody ivonescimab, Capricor’s Duchenne muscular dystrophy cell therapy deramiocel and Vertex’s povetacicept in IgA nephropathy. Finally, check out BioSpace ’s 2027 Best Places to Work list , which includes Vertex and 49 other life sciences employers.

Phase 3Drug ApprovalClinical ResultCell TherapyGene Therapy

09 Nov 2026

·www.fiercepharma.com

FDA opens safety probe into Novartis’ Zolgensma over potential tumor risks

The FDA has launched a safety investigation into Novartis’ gene therapy Zolgensma following reports of tumors in patients, as concerns flare up over genomic insertion risks. Friday, the FDA confirmed it is evaluating cases of tumor formation in children previously treated with Zolgensma for spinal muscular atrophy (SMA). The agency’s diligence extends to Itvisma, a sister intrathecal formulation of the intravenously infused Zolgensma, as the two products contain the same vector and construct, even though Itvisma itself has no reported cases of tumor to date, the FDA said. At the center of the investigation is a biological process known as insertional oncogenesis, where the viral vector used to deliver functional copies of the therapeutic material inserts itself into human genes. Zolgensma relies on an adeno-associated virus vector to deliver a functional SMN1 gene to treat SMA. Rare integration is a known safety risk factor of the treatment. Among more than 6,000 patients that Zolgensma has reached globally, Novartis disclosed nine reports of tumors since its regulatory approval in 2019. These include tumors of the central and peripheral nervous systems, spinal and paraspinal regions, and the kidney, according to the FDA. Molecular analyses performed on tumor tissue from at least two of these patients revealed direct evidence of the therapeutic AAV vector integrating near or within the Glioma-Associated Oncogene Homolog 1 (GLI1), a gene known to cause cancer when overexpressed or abnormally activated, the FDA noted. A third case of GLI1 overexpression is under investigation. In its Nov. 6 communique, the FDA also flagged two recent reports of other gene therapy candidates where AAV vector integration drove tumor formation. One of them is a paraspinal neoplasm case in a 3-year-old boy with infantile-onset Krabbe disease who received FBX-101, developed by Forge Biologics, as part of a clinical trial. The program was discontinued last year as Forge turned its focus to contract manufacturing services following an acquisition by Ajinomoto. In the other case, a neuroepithelial tumor developed in a five-year-old boy with severe mucopolysaccharidosis type I (MPS I) four years after injection with Regenxbio’s RGX-111 into the brain’s fluid-filled cavity. The RGX-111 clinical program has been placed under an FDA clinical hold since January. Despite the investigation, the FDA maintained that the “overall benefits of Zolgensma and Itvisma continue to outweigh their potential risks” in SMA. Zolgensma’s current label already flags a “theoretical risk” of tumor formation due to integration of AAV into the human genome. The FDA now said it’s re-evaluating whether the existing label and long-term studies are sufficient to monitor and mitigate the serious risk of tumors.

AcquisitionGene Therapy

09 Nov 2026

·firstwordpharma.com

Novartis' Zolgensma under FDA scrutiny over tumour reports

The FDA announced that it received postmarketing adverse event reports of malignancies in patients treated with Novartis' Zolgensma (onasemnogene abeparvovec), an AAV9 vector-based gene therapy for spinal muscular atrophy (SMA), and has now launched an investigation. The reports include the formation of tumours in the central and peripheral nervous systems, spinal/paraspinal regions and kidney, along with product-related insertional oncogenesis involving the GLI1 gene, an oncogene that has the potential to cause cancer when overexpressed or abnormally activated."Importantly, three cases involved tumours associated with the GLI1 oncogene. In two of those cases, molecular analysis of tumour tissue demonstrated Zolgensma AAV vector DNA integration into the host genome…The mechanism of GLI1 overexpression in the third case remains under investigation," the FDA said. Additionally, the regulator said it was aware of two published reports of AAV vector integration-driven oncogenesis in other programmes; namely, a GLI1 integration event in the FBX-101 programme that was developed by Forge Biologics before being discontinued last year, and a PLAG1 integration event in REGENXBIO's RGX-111 programme. The FDA placed a hold on RGX-111 in January after an intraventricular CNS tumour was detected in a child who had received the therapy four years earlier.Along with Zolgensma, which received FDA approval in 2019, the US regulator determined that the risk is also applicable to Itvisma, an intrathecal formulation of onasemnogene abeparvovec that was cleared in the US last year to treat SMA in adults and children aged 2 years and older. Although there have been no reported cases of neoplasia following Itvisma administration to date, the two products contain the same vector and construct. "There have been no reported cases of neoplasia following Itvisma administration to date," the FDA said. The agency added it is "closely monitoring the risk of neoplasia, including malignancy, in other similar AAV vector-based gene therapy programmes."Novartis last week confirmed that at least two cases of tumours in children who had received its SMA gene therapy were related to Zolgensma. It also said that since the gene therapy's first approval back in 2019, it has received nine reports of tumours in patients previously treated with Zolgensma.

Gene TherapyDrug ApprovalClinical Result

100 Deals associated with Onasemnogene abeparvovec

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External Link

KEGG	Wiki	ATC	Drug Bank
D11559	Onasemnogene abeparvovec	M09AX M09AX09	DB15528

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
HMN (Hereditary Motor Neuropathy) Proximal Type I	South Korea	Novartis Gene Therapies, Inc.	28 May 2021
Spinal Muscular Atrophy	United States	Novartis Gene Therapies, Inc.	24 May 2019

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Juvenile Spinal Muscular Atrophy	Phase 3	United States	Novartis Gene Therapies, Inc.	10 Feb 2020
Juvenile Spinal Muscular Atrophy	Phase 3	Japan	Novartis Gene Therapies, Inc.	10 Feb 2020
Juvenile Spinal Muscular Atrophy	Phase 3	Australia	Novartis Gene Therapies, Inc.	10 Feb 2020
Juvenile Spinal Muscular Atrophy	Phase 3	Belgium	Novartis Gene Therapies, Inc.	10 Feb 2020
Juvenile Spinal Muscular Atrophy	Phase 3	Canada	Novartis Gene Therapies, Inc.	10 Feb 2020
Juvenile Spinal Muscular Atrophy	Phase 3	France	Novartis Gene Therapies, Inc.	10 Feb 2020
Juvenile Spinal Muscular Atrophy	Phase 3	Italy	Novartis Gene Therapies, Inc.	10 Feb 2020
Juvenile Spinal Muscular Atrophy	Phase 3	Taiwan Province	Novartis Gene Therapies, Inc.	10 Feb 2020
Juvenile Spinal Muscular Atrophy	Phase 3	United Kingdom	Novartis Gene Therapies, Inc.	10 Feb 2020
Muscular Atrophy, Spinal, Type II	Phase 3	Japan	Novartis Gene Therapies, Inc.	02 Apr 2018

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04488133 (RESPOND, CTgov)	Phase 4	Spinal Muscular Atrophy	46	nusinersen (Nusinersen 2 SMN2 Copies)	haicyanahv(btasxgumfp) = szetlshdvn uduukpiorx (ebtxoyhmst, 4.05) View more	-	30 Oct 2026
NCT04488133 (RESPOND, CTgov)	Phase 4	Spinal Muscular Atrophy	46	nusinersen (Nusinersen 3 SMN2 Copies)	haicyanahv(btasxgumfp) = crgpoiozge uduukpiorx (ebtxoyhmst, 7.89) View more	-	30 Oct 2026
NCT04174157 (RESTORE, Pubmed \| Ann Clin Transl Neurol)	Not Applicable	Spinal Muscular Atrophy	80	Onasemnogene Abeparvovec (Spinal Muscular Atrophy)	oedxeapiht(kndsuhmxnb) = gtmfrldmty gwpbglzrqw (havutklyad ) View more	Positive	09 Jun 2026
AAN2026	Not Applicable	Spinal Muscular Atrophy	565	Onasemnogene Abeparvovec Gene Therapy	jqdautpskp(ylozbbaaph) = evvxnyhmgv cefzhbmsfz (agcwcsoosz, 12.07 - 19.47) View more	Positive	25 Apr 2026
NCT02122952 \| NCT03421977 (LT-001, Pubmed \| EClinicalMedicine)	Phase 1	Spinal Muscular Atrophy	13	Onasemnogene abeparvovec	hfinvfflws(hdftxvweso) = ekfxlaehtq jkpkngvvtg (igolseujem ) View more	Positive	01 Apr 2026
RESTORE Registry (MDA2026)	Not Applicable	Spinal Muscular Atrophy	251	Onasemnogene Abeparvovec	qrtpmsouwr(fnyvetgyae) = bwbhzywnao htwgkxvxdv (nhhzeakmxo ) View more	Positive	08 Mar 2026
NCT05089656 (STEER, MDA2026)	Phase 3	Spinal Muscular Atrophy	445	OAV101 IT	ubsnaeqpjd(iigaliqkeb): MD = 1.93 (95.0% CI, -0.25 to 4.1) View more	Positive	08 Mar 2026
NCT05089656 (STEER, MDA2026)	Phase 3	Spinal Muscular Atrophy	445	Risdiplam		Positive	08 Mar 2026
MDA2026	Not Applicable	Spinal Muscular Atrophy	23	Nusinersen	saktleeqgr(bpaejhgjcu) = mngmqajbrc nodxsnfhuc (stnmycshdc, 1.75 - 6.15)	Positive	08 Mar 2026
NCT05089656 (STEER, MDA2026)	Phase 3	Spinal Muscular Atrophy	126	OAV101 IT	sgsubdauvn(zphroxgdqp) = cafexpqslf ydkiqepate (vkyzukmiba, 1.54 - 3.27) View more	Positive	08 Mar 2026
NCT05386680 (STRENGTH, Pubmed \| Nat Med)	Phase 3	Spinal Muscular Atrophy	27	Onasemnogene abeparvovec	uypldoiipd(cemzovsvxa) = ybxofypuqh nqulyyctfa (qqmihxzpil ) View more	Positive	08 Dec 2025
STRENGTH (WCN2025)	Phase 3	Spinal Muscular Atrophy	59	Onasemnogene abeparvovec	tmouwqwwss(laytcqxtls) = The most common AEs were fever (75%, primarily low-grade) and vomiting (47%). Most AEs were mild to moderate in severity and temporary. uxsdtwwcuz (zmlifvqgnv )	Positive	12 Oct 2025