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6ER-007 Real-world effectiveness of gene therapy onasemnogene abeparvovec (Zolgensma) for spinal muscular atrophy: a review
  1. AC Martins De Figueiredo1,
  2. RP Pinheiro Gonçalves Marques2,
  3. AF Cosme Silva2,
  4. AP Mecheiro De Almeida Martins Silvestre Correia1
  1. 1Faculdade de Farmácia da Universidade de Lisboa, Lisbon, Portugal
  2. 2Centro Hospitalar Universitário de Lisboa Norte – Hospital de Santa Maria, Lisbon, Portugal


Background and importance Spinal muscular strophy (SMA) is an autosomal recessive neurodegenerative disorder. SMA I infants have a lifespan of <2 years if not treated. Zolgensma is an innovative drug of gene therapy strategy for SMA patients. Notwithstanding, there remains considerable uncertainty about the long-term sustainability of the Zolgensma clinical effect due to the narrow durability and limited sample size of clinical trials. Therefore, it is essential to measure its effectiveness to increase confidence in the technology use and its market access.

Aim and objectives Our study aimed to provide a critical review of the literature regarding the clinical outcomes in SMA infants in the real-world setting after the one-time Zolgensma dosing.

Material and methods A review of the literature was constructed, comprising five phases: (a) identifying the research question; (b) searching for relevant studies; (c) selecting studies; (d) analysing data and (e) presenting the results. A comprehensive English-language literature search of the electronic databases PubMed and Science Direct was undertaken to identify published papers. Data were collected and analysed until May 2021.

Results In this review, we incorporated one retrospective and one prospective cohort study. In the ongoing prospective Long-Term Follow-Up (LTFU) study (13 patients), 100% of SMA I infants in the therapeutic-dose cohort were alive and free of permanent ventilation. It was reported that 20% of SMA I infants achieved the additional milestone of standing with assistance. The LTFU study has demonstrated that SMA I infants improved their Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) scores (≥4 points). In the retrospective cohort study of SMA I (3 patients) and SMA II infants (4 patients), it was perceived that 43% of SMA patients had meaningful increases in the CHOP-INTEND score and 57% had increases in the Hammersmith Functional Motor Scale-Expanded (HFMSE) score.

Conclusion and relevance Despite the limited observation period, we conclude that Zolgensma is effective since no clinical regression or waning of effect had been reported. Nonetheless, several factors might still influence the duration of Zolgensma’s effectiveness. As such, further research is needed to evaluate the persistence of the Zolgensma real-world effect in SMA infants.

Conflict of interest No conflict of interest

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