Treating SMA Presymptomatically: Respiratory and Nutritional Results from a clinical study

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Novartis Gene Therapies – For spinal muscular atrophy (SMA), the importance of presymptomatic treatment cannot be understated. Children who are identified quickly through newborn screening and genetic testing and are treated before the onset of signs are more likely to have better treatment outcomes than patients who are symptomatic when treated.1

ZOLGENSMA® (onasemnogene abeparvovec-xioi) suspension for intravenous infusion, is a gene therapy indicated for the treatment of pediatric patients less than 2 years of age with spinal muscular atrophy (SMA). ZOLGENSMA has a Boxed Warning for Acute Serious Liver Injury and Acute Liver Failure. Please continue reading below for Important Safety Information and please see accompanying Full Prescribing Information.

What is the SPR1NT trial?

The SPR1NT clinical trial from Novartis Gene Therapies is a completed, open-label study of one-time ZOLGENSMA. The trial enrolled 2 different cohorts of presymptomatic patients—those with 2 copies of the SMN2 gene (n=14), and those with 3 copies of SMN2 (n=15) who all met the inclusion criteria.2-4

Primary and secondary endpoints in SPR1NT2-4:

Event-free survival

100% (29/29) of patients in both the 2-copy and 3-copy cohorts were alive and free of permanent ventilation at the end of the study, which was at 18 months and 24 months, respectively.3,4 

Nutritional independence and weight maintenance


100% (29/29) of patients in both cohorts did not require any kind of feeding support at any time during the trial, up to 18 months of age and 24 months of age, respectively.3,4


In the 2-copy cohort, weight maintenance at or above the 3rd percentile without non-oral or mechanical feeding support at any visit up to the study end at 18 months of age was a secondary endpoint. 93% (13/14) of patients reached this endpoint.3 

Respiratory support

100% (29/29) of patients in both cohorts remained free of any kind of ventilatory support, invasive or noninvasive (including cough assist or BiPAP) through the end of the study at 18 months and 24 months of age, respectively.3,4

For more presymptomatic data from SPR1NT, including motor milestones and motor function, visit

Indication and Important Safety Information
ZOLGENSMA is an adeno-associated virus vector-based gene therapy indicated for the treatment of pediatric patients less than 2 years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene.

Limitations of Use
The safety and effectiveness of repeat administration or the use in patients with advanced SMA (e.g., complete paralysis of limbs, permanent ventilator dependence) has not been evaluated with ZOLGENSMA.

Important Safety Information
BOXED WARNING: Acute Serious Liver Injury and Acute Liver Failure
Acute serious liver injury, acute liver failure, and elevated aminotransferases can occur with ZOLGENSMA. Patients with preexisting liver impairment may be at higher risk. Prior to infusion, assess liver function of all patients by clinical examination and laboratory testing (e.g., hepatic aminotransferases [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], total bilirubin, and prothrombin time). Administer a systemic corticosteroid to all patients before and after ZOLGENSMA infusion. Continue to monitor liver function for at least 3 months after infusion.

Transient decreases in platelet counts, some of which met the criteria for thrombocytopenia, were typically observed within the first two weeks after ZOLGENSMA infusion. Monitor platelet counts before ZOLGENSMA infusion and on a regular basis for at least 3 months afterwards.

Thrombotic Microangiopathy
Cases of thrombotic microangiopathy (TMA) were reported approximately 1 week after ZOLGENSMA infusion. Obtain baseline creatinine and complete blood count before ZOLGENSMA infusion. Following infusion, monitor for thrombocytopenia as well as other signs and symptoms of TMA. Consult a pediatric hematologist and/or pediatric nephrologist immediately to manage if clinically indicated.

Elevated Troponin-I
Increases in cardiac troponin-I levels were observed following ZOLGENSMA infusion. Monitor troponin-I before ZOLGENSMA infusion and on a regular basis for at least 3 months afterwards.

The most commonly observed adverse reactions (incidence ≥5%) in clinical studies were elevated aminotransferases and vomiting.

Please click here for Full Prescribing Information for ZOLGENSMA.

References: 1. Kichula EA, Proud CM, Farrar MA, et al. Expert recommendations and clinical considerations in the use of onasemnogene abeparvovec gene therapy for spinal muscular atrophy. Muscle Nerve. 2021;64(4):413-427. 2. Novartis Gene Therapies, Inc. Pre-symptomatic study of intravenous onasemnogene abeparvovec-xioi in spinal muscular atrophy (SMA) for patients with multiple copies of SMN2 (SPR1NT). identifier: NCT03505099. Updated January 11, 2022. Accessed March 18, 2022. 3. Data on file. Novartis Gene Therapies, Inc. 2021. 4. Data on file. Novartis Gene Therapies, Inc. 2022.

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