• Pharmacology
  • Allergy, Immunology, and ENT
  • Cardiology
  • Emergency Medicine
  • Endocrinology
  • Adolescent Medicine
  • Gastroenterology
  • Infectious Diseases
  • Neurology
  • OB/GYN
  • Practice Improvement
  • Gynecology
  • Respiratory
  • Dermatology
  • Mental, Behavioral and Development Health
  • Oncology
  • Rheumatology
  • Sexual Health
  • Pain

Onasemnogene abeparvovec demonstrates long-term durability for SMA patients


Children treated after presenting spinal muscular atrophy (SMA) symptoms maintained all previously achieved motor milestones up to 7.5 years post-dosing.

SMA block letters | Image Credit: © Rochu_2008 - © Rochu_2008 - stock.adobe.com.

SMA block letters | Image Credit: © Rochu_2008 - © Rochu_2008 - stock.adobe.com.

Onasemnogene abeparvovec (Zolgensma; Novartis) has demonstrated efficacy and durability in 2 long-term follow-up (LTFU) studies as a one-time gene therapy for treating spinal muscular atrophy (SMA), according to a press release from Novartis.

The latest data from the studies LT-001 (NCT03421977) and LT-002 (NCT04042025), presented at the 2023 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference showed benefits of onasemnogene abeparvovec in ranging patient populations.

LT-001 is an ongoing 15-year LTFU study of patients who completed the phase 1 START study. Children in LT-001 who were treated with onasemnogene abeparvovec after presenting SMA symptoms maintained all previously achieved motor milestones up to 7.5 years after the one-time intravenous infusion. Standing with assistance, the key milestone was achieved by 3 additional patients during the study period.

Of the 12 patients from cohort 2 (therapeutic dose) of the phase 1 START study, 10 voluntarily enrolled in the 15-year ongoing LT-001 study. The mean age of patients in this study was 7.1 years, with a mean time of 6.86 years since administration of gene therapy treatment.

As of the May 23, 2022, data cut-off, all patients in the therapeutic dose cohort (n = 10) were alive and free of permanent ventilation, maintained previously achieved milestones, and were fed orally. Feeding support was not required in 4 of the 10 patients.

Daily ventilatory support with bilevel positive airway pressure (BiPAP) was not required in 70% of patients more than 7 years post-dosing, demonstrating a decrease in overall ventilatory support use. Of the 10 patients in LT-001, 4 did not receive add-on therapy in the follow-up period. Of the 6 that did, 5 did not achieve a new motor milestone.

Of the 3 patients that achieved the key milestone of standing with assistance during the follow-up period, 2 achieved the milestone without add-on therapy, while the remaining patient achieved it after the addition of nusinersen (SPINRAZA; Biogen).

No serious treatment-emergent adverse events (TEAEs) were related to treatment during the study, and no serious TEAEs resulted in study discontinuation. Acute respiratory failure, dehydration, and pneumonia were the most frequently reported events, with each present in 5 patients (38.5%). No new safety signals were identified.

LT-002 included both presymptomatic and symptomatic patient populations and intravenous (IV) and intrathecal (IT) administration methods. All 81 patients in LT-002, across all cohorts and parent studies, maintained previously achieved motor milestones.

LT-002 is an ongoing, voluntary, phase 4, follow-up study of onasemnogene abeparvovec IV in patients previously treated in phase 3 studies STR1VE-US, STR1VE-EU, STR1VE-AP, SPR1NT and the phase 1 IT study (STRONG).

The IV cohort featured 63 patients and demonstrated how a single administration of onasemnogene abeparvovec provided durable efficacy over time. The mean age of patents in this cohort was 3.7 years, with a mean follow-up time of 3.4 years. In the presymptomatic IV cohort (n = 25), all children either maintained walking alone, the highest milestone achieved during the parent study, or achieved the milestone by data cut-off (May 23, 2022).

Of the symptomatic patients in LT-002, 32 achieved or maintained the milestone of sitting without support. Clinically significant improvement of 3 or more points in Hammersmith Functional Motor Scale and Motor Function Measure (HFSME) was demonstrated in 13 (81.3%) patients treated before SMA symptom onset and 18 (66.7%) patients treated after SMA symptom onset.

The IT cohort contained 18 patients, with a mean age of 5.3 years and a mean follow-up of 3.6 years. All patients in the follow-up period demonstrated continued gains and stability in motor function with the achievement of new motor milestones, and maintenance of already achieved milestones.

In patients with at least 2 assessments available, 6 of 12 demonstrated a clinically significant improvement of 3 or more points in HFMSE, and 3 had more than a 10-point improvement. Of the 16 patients with at least 1 milestone assessment, 5 achieved a new motor milestone in LT-002.

Of the 81 total patients in LT-002, 77 had at least 1 milestone assessment. Of those, 48 (62.3%) either achieved a new motor milestone in the study or had already achieved all motor milestones in the parent study, according to the press release.


Novartis shares Zolgensma long-term data demonstrating sustained durability up to 7.5 years post-dosing; 100% achievement of all assessed milestones in children treated prior to SMA symptom onset. Novartis. March 20, 2023. Accessed March 28, 2023. https://www.novartis.com/news/media-releases/novartis-shares-zolgensma-long-term-data-demonstrating-sustained-durability-75-years-post-dosing-100-achievement-all-assessed-milestones-children-treated-prior-sma-symptom-onset

Related Videos
Venous thromboembolism, Heparin-induced thrombocytopenia, and direct oral anticoagulants | Image credit: Contemporary Pediatrics
Sally Humphrey, DNP, APRN, CPNP-PC | Image Credit: Contemporary Pediatrics
Ashley Gyura, DNP, CPNP-PC | Image Credit: Children's Minnesota
Congenital heart disease and associated genetic red flags
Traci Gonzales, MSN, APRN, CPNP-PC
Scott Ceresnak, MD
© 2024 MJH Life Sciences

All rights reserved.