Treatment of spinal muscular atrophy with Onasemnogene Abeparvovec in Switzerland: a prospective observational case series study

Abstract

Background Spinal muscular atrophy (SMA) is a rare neuromuscular disorder leading to early death in the majority of affected individuals without treatment. Recently, targeted treatment approaches including Onasemnogene Abeparvovec (OA) were introduced. This study describes the first real-world experience with OA in Switzerland. Methods Prospective observational case series study using data collected within the Swiss Registry for Neuromuscular Disorders from SMA patients treated with OA. Development of motor, bulbar and respiratory function, appearance of scoliosis, and safety data (platelet count, liver function, and cardiotoxicity) were analyzed. Results Nine individuals were treated with OA and followed for 383 ± 126 days: six SMA type 1 (of which two with nusinersen pretreatment), one SMA type 2, and two pre-symptomatic individuals. In SMA type 1, CHOP Intend score increased by 28.1 from a mean score of 20.5 ± 7.6 at baseline. At end of follow-up, 50% of SMA type 1 patients required nutritional support and 17% night-time ventilation; 67% developed scoliosis. The SMA type 2 patient and two pre-symptomatically treated individuals reached maximum CHOP Intend scores. No patient required adaptation of the concomitant prednisolone treatment, although transient decrease of platelet count and increase of transaminases were observed in all patients. Troponin-T was elevated prior to OA treatment in 100% and showed fluctuations in 57% thereafter. Conclusions OA is a potent treatment for SMA leading to significant motor function improvements. However, the need for respiratory and especially nutritional support as well as the development of scoliosis must be thoroughly evaluated in SMA type 1 patients even in the short term after OA treatment.

Efficacy and safety of onasemnogene abeparvovec in children with spinal muscular atrophy type 1: real-world evidence from 6 infusion centres in the United Kingdom

“…In contrast to untreated children with SMA type 1, 23 , 24 , 25 children treated with OA have consistently achieved CHOP-INTEND scores of at least 40 in both trial and real-world settings. 26 , 27 , 28 , 29 , 30 In this study, over 80% of patients showed an increase in CHOP-INTEND score after OA, indicating improvements in motor function, most notably in younger patients. Although the average improvement in CHOP-INTEND score after OA was less in older patients, a small number of patients aged 24 months or older did make significant gains.…”

Consensus from the Brazilian Academy of Neurology for the diagnosis, genetic counseling, and use of disease-modifying therapies in 5q spinal muscular atrophy

“…These real-world studies have confirmed the efficacy of the gene replacement therapy in an expanded age range of patients eligible for treatment, including those up to two years old and also patients with three copies of SMN2 , regardless of the type of SMA. 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 Additionally, some studies have evaluated the use of onasemnogene abeparvovec in patients who had previously been treated with other specific therapies, such as nusinersen or risdiplam. 102 103 105 106 108 …”

“… 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 Additionally, some studies have evaluated the use of onasemnogene abeparvovec in patients who had previously been treated with other specific therapies, such as nusinersen or risdiplam. 102 103 105 106 108 …”

“…Real-world studies conducted in various countries, particularly those linked to expanded newborn screening (NBS) programs, have consistently shown that early initiation of gene replacement therapy in pre-symptomatic infants with SMA-5q results in remarkable developmental progress, with children achieving motor milestones within the expected developmental timeframe. 108 113 114 115 Furthermore, cost-effectiveness studies, particularly in countries like Australia, have shown that implementing neonatal screening for SMA-5q, coupled with early gene replacement therapy treatment, leads to reduced costs or remains within the cost-effectiveness threshold considered by these countries in the long term. 116 …”

Treatment of Symptomatic Spinal Muscular Atrophy with Nusinersen: A Prospective Longitudinal Study on Scoliosis Progression

“…The child experienced rapid scoliosis progression and had magnetic growing rods inserted at 18 months of age. Another prospective observational study from Switzerland [ 27 ] involved six symptomatic SMA1 patients with 2 SMN2 copies receiving early Onasemnogene Abeparvovec ( n = 4) or bridging nusinersen then Onasemnogene Abeparvovec ( n = 2) before 6 months of age. All patients showed meaningful improvement in CHOP-INTEND Scores.…”