ABSTRACT Background As a rare disease with the largest number of cases in China, spinal muscular atrophy (SMA) causes severe motor deficits as well as multi-system organ damage. Some potent drugs for SMA, such as Nusinersen (NU) and Risdiplam (RI) represented by targeted survival motor neuron gene therapy, have become a new trend in the treatment of SMA. RI has gradually attracted attention due to its ease of administration, safety, and efficacy. Objective The study was to analyze the cost-effectiveness of RI and NU for the treatment of SMA in China from the perspective of the healthcare system. Methods We constructed a five-state Markov model based on the different stages of SMA. The willingness-to-pay threshold was chosen to be 1-3 times the gross domestic product (GDP) per capita. The base-case analysis was used to calculate the incremental cost-effectiveness ratio (ICER), and one-way and probabilistic sensitivity analyses were performed. Results The ICER value was ¥132,402.10/QALY, which was in the range of 1-3 times GDP per capita. Sensitivity analysis results showed the cost of RI and NU had a significant effect on ICER as well as proving the stability of results. Conclusions RI is a cost-effective option compared to NU in SMA treatment.

Differential respiratory function response in paediatric spinal muscular atrophy types 2 and 3 treated with nusinersen over 3 years.

The quality control of oligonucleotides using separation analytical methods is complicated owing to co-elution of structurally similar impurities and active oligonucleotides. Thus, the inadequate separation of impurities from the active pharmaceutical ingredients restricts the applicability of these assay methods. This limitation also hinders achieving compliance with regulatory standards. Accordingly, this research was focused on the development of an assay methodology for tofersen (TSN) to enable accurate quantification despite the presence of co-eluting impurities. An analytical assay method for the determination of TSN was proposed based on ion-pair reverse-phase liquid chromatography coupled with high-resolution mass spectrometry using an extracted ion chromatography processing approach. Nusinersen (NSN) was utilized as the internal standard to mitigate variations in signal intensity of the mass spectrometer. The developed method was validated according to the ICH Q2(R2) and USP regulatory frameworks. The method demonstrated linear response and specificity within the concentration range of 3-10 μg mL-1. The recovery from the formulation matrix, which was determined using the standard addition method with triplicate measurements at three concentration levels, was found to be within the range of 80-120%. Furthermore, the method exhibited precision and robustness for critical liquid chromatography parameters, such as flow rate and injection volume, and mass spectrometer parameters, including drying/desolvation temperature and gas flow.

A new respiratory scoring system for evaluation of respiratory outcomes in children with spinal muscular atrophy type1 (SMA1) on SMN enhancing drugs

A atrofia muscular espinhal (AME) é um tipo de doença neuromuscular específica, causada pela degeneração dos motoneurônios, resultando em atrofias e fraqueza muscular progressiva. A utilização de medicamentos associado à reabilitação buscam proporcionar mais qualidade de vida ao indivíduo e a família. O objetivo foi verificar o nível de percepção das famílias de pacientes com AME sobre a eficácia do uso da medicação Spinraza® associada à fisioterapia. Trata-se de um estudo transversal, quanti-qualitativo, realizado por meio de um formulário online enviado às famílias de indivíduos com AME de todo Brasil, as quais responderam a um questionário semiestruturado com perguntas relacionadas ao uso do medicamento Spinraza® e o tratamento fisioterapêutico. Foi realizada a estatística descritiva. Participaram 114 famílias, sendo que 60% havia indivíduos que fazem uso do fármaco. Em relação ao tratamento fisioterapêutico, apenas 1 criança não faz o acompanhamento com este profissional. A maioria dos familiares (53%) destacou que perceberam maiores avanços no tratamento com a fisioterapia associada ao uso do medicamento e 8% desses, acreditam que somente a fisioterapia já é suficiente. Conclui-se que os familiares de indivíduos com AME apresentam uma percepção positiva da melhora do quadro clínico quando o mesmo realiza o uso do medicamento Spinraza® associado à fisioterapia. Nesse sentido, a combinação de ambas as abordagens de tratamento devem sem incentivadas para impedir a progressão da AME, proporcionando melhor qualidade de vida para o indivíduo e a família.

SMA - CLINICAL: P.92 Comparing motor and respiratory function in SMA Type1 treated with Nusinersen using CHOP INTEND(CHOP) & Great Ormond Street Respiratory Score(GSR)

Nusinersen in SMA 2 and 3: Risks vs benefits.

Nusinersen is approved for treatment of all patients with spinal muscular atrophy (SMA), but its efficacy has been demonstrated in only infants and

Background/Objectives: Hip instability is common in patients with Spinal Muscular Atrophy (SMA), but traditionally has been treated non-operatively due to operative risks and minimal data to support the benefits of hip reconstructive surgery in non-ambulatory SMA patients. In a survey of Cure SMA patients, 60% reported pain in their lower extremities “some” or “all the time” irrespective of ambulatory status, yet treatment with Nusinersen has increased the ambulatory potential of these patients. The purpose of this study was to evaluate the short-term clinical outcomes …

To review the efficacy and safety of nusinersen (Spinraza) in the treatment of spinal muscular atrophy (SMA). An English-language literature search of PubMed and MEDLINE (1946 to June 2018) was performed using the terms nusinersen, ISIS-SMN (Rx), and spinal muscular atrophy. Manufacturer prescribing information, abstracts, article bibliographies, and clinicaltrials.gov data were incorporated for additional materials. All clinical trials of nusinersen were identified and analyzed in the review. Nusinersen is the first drug therapy approved for the treatment of SMA. It is a novel modified antisense oligonucleotide designed to treat SMA caused by mutations in chromosome 5q that lead to survival motor neuron protein deficiency. Nusinersen has been studied for safety, pharmacokinetics, and efficacy in both open-label and randomized controlled trials. The studies show improvement in motor function across SMA of all types. The most common adverse effects were respiratory tract infections, headache, back pain, constipation, and post-lumbar puncture syndrome. Relevance to Patient Care and Clinical Practice: Based on phase III trial data, nusinersen produced positive changes in the clinical course of patients with SMA. The acquisition and administration of nusinersen present a number of challenges in clinical practice. Its intrathecal delivery and costly price tag must be recognized. Nusinersen is safe and effective in patients with SMA. It was well tolerated across all studied age groups.

Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease caused by homozygous deletion of the SMN1 gene, producing insufficient

Efficacy and safety of nusinersen in children with later-onset spinal muscular atrophy (SMA): results of the phase 3 CHERISH study

Motor neuron disease: Nusinersen potentially effective in SMA.