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References
Contents
Academic Editor
- Julio Pardo Fernández
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[1]Lunn MR, Wang CH. Spinal muscular atrophy. Lancet (London, England). 2008; 371: 2120–2133. https://doi.org/10.1016/S0140-6736(08)60921-6.
[2]Alías L, Bernal S, Fuentes-Prior P, Barceló MJ, Also E, Martínez-Hernández R, et al. Mutation update of spinal muscular atrophy in Spain: molecular characterization of 745 unrelated patients and identification of four novel mutations in the SMN1 gene. Human Genetics. 2009; 125: 29–39. https://doi.org/10.1007/s00439-008-0598-1.
[3]AEMPS. Informe de Posicionamiento Terapéutico de nusinersen (Spinraza®) en atrofia muscular espinal. vol. 1. 2018. Available at: https://www.aemps.gob.es/medicamentosUsoHumano/informesPublicos/docs/IPT-nusinersen-Spinraza-atrofia-muscular-espinal.pdf (Accedido: 26 de Julio de 2024)
[4]Lefebvre S, Bürglen L, Reboullet S, Clermont O, Burlet P, Viollet L, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995; 80: 155–165. https://doi.org/10.1016/0092-8674(95)90460-3.
[5]Vitte J, Fassier C, Tiziano FD, Dalard C, Soave S, Roblot N, et al. Refined characterization of the expression and stability of the SMN gene products. The American Journal of Pathology. 2007; 171: 1269–1280. https://doi.org/10.2353/ajpath.2007.070399.
[6]Mercuri E, Finkel RS, Muntoni F, Wirth B, Montes J, Main M, et al. Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscular Disorders: NMD. 2018; 28: 103–115. https://doi.org/10.1016/j.nmd.2017.11.005.
[7]Talbot K, Tizzano EF. The clinical landscape for SMA in a new therapeutic era. Gene Therapy. 2017; 24: 529–533. https://doi.org/10.1038/gt.2017.52.
[8]Calucho M, Bernal S, Alías L, March F, Venceslá A, Rodríguez-Álvarez FJ, et al. Correlation between SMA type and SMN2 copy number revisited: An analysis of 625 unrelated Spanish patients and a compilation of 2834 reported cases. Neuromuscular Disorders: NMD. 2018; 28: 208–215. https://doi.org/10.1016/j.nmd.2018.01.003.
[9]Pitarch Castellano I, Cabrera-Serrano M, Calvo Medina R, Cattinari MG, Espinosa García S, Fernández-Ramos JA, et al. Consenso Delphi de las recomendaciones para el tratamiento de los pacientes con atrofia muscular espinal en España (consenso RET-AME). Neurología. 2022; 37: 216–228. https://doi.org/10.1016/j.nrl.2021.07.008.
[10]Wadman RI, Wijngaarde CA, Stam M, Bartels B, Otto LAM, Lemmink HH, et al. Muscle strength and motor function throughout life in a cross-sectional cohort of 180 patients with spinal muscular atrophy types 1c-4. European Journal of Neurology. 2018; 25: 512–518. https://doi.org/10.1111/ene.13534.
[11]Schorling DC, Pechmann A, Kirschner J. Advances in treatment of spinal muscular atrophy - new phenotypes, new challenges, new implications for care. Journal of Neuromuscular Diseases. 2020; 7: 1–13. https://doi.org/10.3233/JND-190424.
[12]Kolb SJ, Kissel JT. Spinal Muscular Atrophy. Neurologic Clinics. 2015; 33: 831–846. https://doi.org/10.1016/j.ncl.2015.07.004.
[13]Finkel RS, Mercuri E, Meyer OH, Simonds AK, Schroth MK, Graham RJ, et al. Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics. Neuromuscular Disorders: NMD. 2018; 28: 197–207. https://doi.org/10.1016/j.nmd.2017.11.004.
[14]European Medicines Agency. FICHA TÉCNICA SPINRAZA®. 2017. Available at: https://www.ema.europa.eu/en/documents/product-information/spinraza-epar-product-information_es.pdf (Accedido: 29 de Diciembre de 2022).
[15]European Medicines Agency. FICHA TÉCNICA ZOLGENSMA®. 2020. Available at: https://www.ema.europa.eu/en/documents/product-information/zolgensma-epar-product-information_en.pdf (Accedido: 26 de Julio de 2024).
[16]European Medicines Agency. FICHA TÉCNICA EVRISDY®. 2021. Available at: https://www.ema.europa.eu/en/documents/product-information/evrysdi-epar-product-information_es.pdf (Accedido: 10 de Enero de 2023).
[17]ClinicalTrials.gov. A study to evaluate the efficacy and safety of taldefgrobep alfa in participants with spinal muscular atrophy (RESILIENT). Identifier NCT05337553. 2023. Available at: https://clinicaltrials.gov/study/NCT05337553 (Accedido: 26 de Julio de 2024).
[18]ClinicalTrials.gov. A study to investigate the safety and efficacy of RO7204239 in combination with Risdiplam (RO7034067) in participants with spinal muscular atrophy. Identifier NCT05115110. 2022. Available at: https://clinicaltrials.gov/study/NCT05115110 (Accedido: 26 de Julio de 2024).
[19]ClinicalTrials.gov. A study to evaluate the safety, tolerability, and efficacy of srk-015 in patients with Type 2 or Type 3 spinal muscular atrophy (TOPAZ): Identifier NCT03921528. 2019. Available at: https://doi.org/10.31525/ct1-nct03921528 (Accedido: 26 de Julio de 2024).
[20]ClinicalTrials.gov. Safety and efficacy of NMD670 in ambulatory adult patients with type 3 spinal muscular atrophy (SYNAPSE-SMA). Identifier NCT05794139. 2023. Available at: https://clinicaltrials.gov/study/NCT05794139 (Accedido: 26 de Julio de 2024).
[21]Farmacia DG de CB de S del S y. Protocolo Farmacolínico del tratamiento con ONASEMNOGÉN ABEPARVOVEC (ZOLGENSMA®) en pacientes con Atrofia Muscular Espinal. 2022. Available at: https://www.sanidad.gob.es/areas/farmacia/infoMedicamentos/valtermed/docs/20220408_Protocolo_farmacoclinico_Zolgensma_AME.pdf (Accedido: 26 de Julio de 2024)
[22]Farmacia DG de CB de S del S y. Protocolo clínico de uso de Nusinersen y Risdiplam para la Atrofia Muscular Espinal (AME) en el Sistema Nacional de Salud 2024:27052–3. Available at: https://www.sanidad.gob.es/areas/farmacia/infoMedicamentos/valtermed/docs/20240219_Protocol_AME.pdf (Accedido: 26 de Julio de 2024).
[23]Farmacia DG de CB de S del S y. Protocolo Farmacolínico del tratamiento con NUSINERSEN (SPINRAZA®)en pacientes con Atrofia Muscular Espinal. Madrid: 2018. Available at: http://genm.sen.es/attachments/article/164/protocolo_tratamiento_nusinersen_ame.pdf . (Accedido: 26 de Julio de 2024)
[24]Cattinari MG, de Lemus M, Tizzano E. RegistrAME: the Spanish self-reported patient registry of spinal muscular atrophy. Orphanet Journal of Rare Diseases. 2024; 19: 76. https://doi.org/10.1186/s13023-024-03071-7.
[25]Gliklich R, Dreyer N, Leavy M. Rare disease registries. Agency for Healthcare Research and Quality: US. 2014.
[26]de Lemus M, Cattinari MG, Pascual SI, Medina J, García M, Magallón A, et al. Identification of the most relevant aspects of spinal muscular atrophy (SMA) with impact on the quality of life of SMA patients and their caregivers: the PROfuture project, a qualitative study. Journal of Patient-reported Outcomes. 2024; 8: 78. https://doi.org/10.1186/s41687-024-00758-0.
[27]Lemoine M, Gomez M, Grimaldi L, Urtizberea JA, Quijano-Roy S. The SMA France national registry: already encouraging results. Medecine Sciences: M/S. 2021; 37 Hors série n° 1: 25–29. https://doi.org/10.1051/medsci/2021187.
[28]Lusakowska A, Jedrzejowska M, Kaminska A, Janiszewska K, Grochowski P, Zimowski J, et al. Observation of the natural course of type 3 spinal muscular atrophy: data from the polish registry of spinal muscular atrophy. Orphanet Journal of Rare Diseases. 2021; 16: 150. https://doi.org/10.1186/s13023-021-01771-y.
[29]Coratti G, Ricci M, Capasso A, D’amico A, Sansone V, Bruno C, et al. Prevalence of Spinal Muscular Atrophy in the Era of Disease-Modifying Therapies: An Italian Nationwide Survey. Neurology. 2023; 100: 522–528. https://doi.org/10.1212/WNL.0000000000201654.
[30]Zerres K, Rudnik-Schöneborn S, Forkert R, Wirth B. Genetic basis of adult-onset spinal muscular atrophy. Lancet (London, England). 1995; 346: 1162. https://doi.org/10.1016/s0140-6736(95)91835-3.
[31]Russman BS. Spinal muscular atrophy: clinical classification and disease heterogeneity. Journal of Child Neurology. 2007; 22: 946–951. https://doi.org/10.1177/0883073807305673.
[32]Gusset N, Stalens C, Stumpe E, Klouvi L, Mejat A, Ouillade MC, et al. Understanding European patient expectations towards current therapeutic development in spinal muscular atrophy. Neuromuscular Disorders: NMD. 2021; 31: 419–430. https://doi.org/10.1016/j.nmd.2021.01.012.
[33]Cattinari M, Hervás D, Lemus M De, Tizzano E. Beyond the “walker” label: functional diversity and disease impact in spinal muscular atrophy patients with walking ability (P134). Neuromuscular Disorders: NMD. 2024; 43: 104441. https://doi.org/10.1016/j.nmd.2024.07.041.
[34]Vázquez-Costa JF, Branas-Pampillón M, Medina-Cantillo J, Povedano M, Pitarch-Castellano I, López-Lobato M, et al. Validation of a Set of Instruments to Assess Patient- and Caregiver-Oriented Measurements in Spinal Muscular Atrophy: Results of the SMA-TOOL Study. Neurology and Therapy. 2023; 12: 89–105. https://doi.org/10.1007/s40120-022-00411-2.
[35]Gómez-Andrés D, Martínez-Moreno M, Vázquez-Costa JF. Treatment of patients with spinal muscular atrophy 5q: Towards a new protocol. Neurologia. 2020; 36: 636–637. https://doi.org/10.1016/j.nrleng.2020.10.005.
[36]AEMPS Agencia Española de Medicamentos y Productos Sanitarios. REEC - Registro Español de Estudios Clínicos n.d. 2022. Available at: https://reec.aemps.es/reec/public/list.html (Accedido: 26 de Julio de 2024).
[37]Roche. Access to investigational medicines outside of a clinical trial n.d. 2020. Available at: https://www.roche.com/innovation/process/clinical-trials/investigational-medicines (Accedido: 13 de Enero de 2023).
[38]FundAME. EL ACCESO AL USO COMPASIVO DEL MEDICAMENTO “SPINRAZA” PARA AFECTADOS DE AME TIPO 1 HA DADO COMIENZO EN ESPAÑA. 2017. Available at: https://www.fundame.net/el-acceso-al-uso-compasivo-del-medicamento-spinraza-para-afectados-de-ame-tipo-1-ha-dado-comienzo-en-espana-2/ (Accedido: 2 de Mayo de 2023).
Academic Editor
- Julio Pardo Fernández
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, Mencía De Lemus 1,2,3, Maria Dumont 1, Eduardo Tizzano 4,51 Fundación de Atrofia Muscular Espinal, FundAME, 28034 Madrid, España
2 SMA Europe, 79112 Freiburg, Germany
3 Committee of Advanced Therapies at the European Medicines Agency, 1083 HS Amsterdam, The Netherlands
4 Medical Genetics Group, Rare Diseases Unit, Department of Clinical and Molecular Genetics, Vall d'Hebron Research Institute, Hospital Valle Hebron, 08035 Barcelona, España
5 CIBERER, Barcelona, España
Abstract
Spinal muscular atrophy (SMA) is a neurodegenerative disease in which there has been an increase in survivalover the past decade due to proactive, multidisciplinary management and the emergence of disease-modifying therapies.Despite this, there are still several critical challenges that significantly impact the quality of life of individuals with SMAindividuals. Given the need to better understand the reality of this disease, Fundación de Atrofia Muscular Espinal (FundAME)created a patient registry (RegistrAME).
RegistrAME is a longitudinal prospective study that collectsclinical data and patient-reported outcomes.
The registry included 336 individuals, 51.8% of whom were over16 years old. Most adult subpopulations were classed as type 2 (49.4%) or type 3 (44.8%). Regarding functional status,19% walked (39.4% used wheelchairs), 46.6% sat without support (84% needed help to sit), and 34.5% were non-sitters.Furthermore, 24.7% reported having no useful function in their hands or not being able to reach their mouths with theirhands. Our study indicates that the adult SMA population is progressively accessing disease-modifier treatments. However,21.8% of the population is still untreated.
These results provide evidence of a progressive impairment andincreased sensitivity to treatment discontinuations in the SMA adult population, along with delayed or reduced access tocommercialised SMA drugs and clinical trials. A more rigorous evaluation of the disease’s impact and treatment benefitsin the adult SMA population is necessary.
Keywords
- spinal muscular atrophy
- neuromuscular disorders
- patient registry
- rare disease
- real-life outcome data
- treatment access
- adult patient
- RegistrAME
- self-reported registry
References
- [1]
Lunn MR, Wang CH. Spinal muscular atrophy. Lancet (London, England). 2008; 371: 2120–2133. https://doi.org/10.1016/S0140-6736(08)60921-6. - [2]
Alías L, Bernal S, Fuentes-Prior P, Barceló MJ, Also E, Martínez-Hernández R, et al. Mutation update of spinal muscular atrophy in Spain: molecular characterization of 745 unrelated patients and identification of four novel mutations in the SMN1 gene. Human Genetics. 2009; 125: 29–39. https://doi.org/10.1007/s00439-008-0598-1. - [3]
AEMPS. Informe de Posicionamiento Terapéutico de nusinersen (Spinraza®) en atrofia muscular espinal. vol. 1. 2018. Available at: https://www.aemps.gob.es/medicamentosUsoHumano/informesPublicos/docs/IPT-nusinersen-Spinraza-atrofia-muscular-espinal.pdf (Accedido: 26 de Julio de 2024) - [4]
Lefebvre S, Bürglen L, Reboullet S, Clermont O, Burlet P, Viollet L, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995; 80: 155–165. https://doi.org/10.1016/0092-8674(95)90460-3. - [5]
Vitte J, Fassier C, Tiziano FD, Dalard C, Soave S, Roblot N, et al. Refined characterization of the expression and stability of the SMN gene products. The American Journal of Pathology. 2007; 171: 1269–1280. https://doi.org/10.2353/ajpath.2007.070399. - [6]
Mercuri E, Finkel RS, Muntoni F, Wirth B, Montes J, Main M, et al. Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscular Disorders: NMD. 2018; 28: 103–115. https://doi.org/10.1016/j.nmd.2017.11.005. - [7]
Talbot K, Tizzano EF. The clinical landscape for SMA in a new therapeutic era. Gene Therapy. 2017; 24: 529–533. https://doi.org/10.1038/gt.2017.52. - [8]
Calucho M, Bernal S, Alías L, March F, Venceslá A, Rodríguez-Álvarez FJ, et al. Correlation between SMA type and SMN2 copy number revisited: An analysis of 625 unrelated Spanish patients and a compilation of 2834 reported cases. Neuromuscular Disorders: NMD. 2018; 28: 208–215. https://doi.org/10.1016/j.nmd.2018.01.003. - [9]
Pitarch Castellano I, Cabrera-Serrano M, Calvo Medina R, Cattinari MG, Espinosa García S, Fernández-Ramos JA, et al. Consenso Delphi de las recomendaciones para el tratamiento de los pacientes con atrofia muscular espinal en España (consenso RET-AME). Neurología. 2022; 37: 216–228. https://doi.org/10.1016/j.nrl.2021.07.008. - [10]
Wadman RI, Wijngaarde CA, Stam M, Bartels B, Otto LAM, Lemmink HH, et al. Muscle strength and motor function throughout life in a cross-sectional cohort of 180 patients with spinal muscular atrophy types 1c-4. European Journal of Neurology. 2018; 25: 512–518. https://doi.org/10.1111/ene.13534. - [11]
Schorling DC, Pechmann A, Kirschner J. Advances in treatment of spinal muscular atrophy - new phenotypes, new challenges, new implications for care. Journal of Neuromuscular Diseases. 2020; 7: 1–13. https://doi.org/10.3233/JND-190424. - [12]
Kolb SJ, Kissel JT. Spinal Muscular Atrophy. Neurologic Clinics. 2015; 33: 831–846. https://doi.org/10.1016/j.ncl.2015.07.004. - [13]
Finkel RS, Mercuri E, Meyer OH, Simonds AK, Schroth MK, Graham RJ, et al. Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics. Neuromuscular Disorders: NMD. 2018; 28: 197–207. https://doi.org/10.1016/j.nmd.2017.11.004. - [14]
European Medicines Agency. FICHA TÉCNICA SPINRAZA®. 2017. Available at: https://www.ema.europa.eu/en/documents/product-information/spinraza-epar-product-information_es.pdf (Accedido: 29 de Diciembre de 2022). - [15]
European Medicines Agency. FICHA TÉCNICA ZOLGENSMA®. 2020. Available at: https://www.ema.europa.eu/en/documents/product-information/zolgensma-epar-product-information_en.pdf (Accedido: 26 de Julio de 2024). - [16]
European Medicines Agency. FICHA TÉCNICA EVRISDY®. 2021. Available at: https://www.ema.europa.eu/en/documents/product-information/evrysdi-epar-product-information_es.pdf (Accedido: 10 de Enero de 2023). - [17]
ClinicalTrials.gov. A study to evaluate the efficacy and safety of taldefgrobep alfa in participants with spinal muscular atrophy (RESILIENT). Identifier NCT05337553. 2023. Available at: https://clinicaltrials.gov/study/NCT05337553 (Accedido: 26 de Julio de 2024). - [18]
ClinicalTrials.gov. A study to investigate the safety and efficacy of RO7204239 in combination with Risdiplam (RO7034067) in participants with spinal muscular atrophy. Identifier NCT05115110. 2022. Available at: https://clinicaltrials.gov/study/NCT05115110 (Accedido: 26 de Julio de 2024). - [19]
ClinicalTrials.gov. A study to evaluate the safety, tolerability, and efficacy of srk-015 in patients with Type 2 or Type 3 spinal muscular atrophy (TOPAZ): Identifier NCT03921528. 2019. Available at: https://doi.org/10.31525/ct1-nct03921528 (Accedido: 26 de Julio de 2024). - [20]
ClinicalTrials.gov. Safety and efficacy of NMD670 in ambulatory adult patients with type 3 spinal muscular atrophy (SYNAPSE-SMA). Identifier NCT05794139. 2023. Available at: https://clinicaltrials.gov/study/NCT05794139 (Accedido: 26 de Julio de 2024). - [21]
Farmacia DG de CB de S del S y. Protocolo Farmacolínico del tratamiento con ONASEMNOGÉN ABEPARVOVEC (ZOLGENSMA®) en pacientes con Atrofia Muscular Espinal. 2022. Available at: https://www.sanidad.gob.es/areas/farmacia/infoMedicamentos/valtermed/docs/20220408_Protocolo_farmacoclinico_Zolgensma_AME.pdf (Accedido: 26 de Julio de 2024) - [22]
Farmacia DG de CB de S del S y. Protocolo clínico de uso de Nusinersen y Risdiplam para la Atrofia Muscular Espinal (AME) en el Sistema Nacional de Salud 2024:27052–3. Available at: https://www.sanidad.gob.es/areas/farmacia/infoMedicamentos/valtermed/docs/20240219_Protocol_AME.pdf (Accedido: 26 de Julio de 2024). - [23]
Farmacia DG de CB de S del S y. Protocolo Farmacolínico del tratamiento con NUSINERSEN (SPINRAZA®)en pacientes con Atrofia Muscular Espinal. Madrid: 2018. Available at: http://genm.sen.es/attachments/article/164/protocolo_tratamiento_nusinersen_ame.pdf . (Accedido: 26 de Julio de 2024) - [24]
Cattinari MG, de Lemus M, Tizzano E. RegistrAME: the Spanish self-reported patient registry of spinal muscular atrophy. Orphanet Journal of Rare Diseases. 2024; 19: 76. https://doi.org/10.1186/s13023-024-03071-7. - [25]
Gliklich R, Dreyer N, Leavy M. Rare disease registries. Agency for Healthcare Research and Quality: US. 2014. - [26]
de Lemus M, Cattinari MG, Pascual SI, Medina J, García M, Magallón A, et al. Identification of the most relevant aspects of spinal muscular atrophy (SMA) with impact on the quality of life of SMA patients and their caregivers: the PROfuture project, a qualitative study. Journal of Patient-reported Outcomes. 2024; 8: 78. https://doi.org/10.1186/s41687-024-00758-0. - [27]
Lemoine M, Gomez M, Grimaldi L, Urtizberea JA, Quijano-Roy S. The SMA France national registry: already encouraging results. Medecine Sciences: M/S. 2021; 37 Hors série n° 1: 25–29. https://doi.org/10.1051/medsci/2021187. - [28]
Lusakowska A, Jedrzejowska M, Kaminska A, Janiszewska K, Grochowski P, Zimowski J, et al. Observation of the natural course of type 3 spinal muscular atrophy: data from the polish registry of spinal muscular atrophy. Orphanet Journal of Rare Diseases. 2021; 16: 150. https://doi.org/10.1186/s13023-021-01771-y. - [29]
Coratti G, Ricci M, Capasso A, D’amico A, Sansone V, Bruno C, et al. Prevalence of Spinal Muscular Atrophy in the Era of Disease-Modifying Therapies: An Italian Nationwide Survey. Neurology. 2023; 100: 522–528. https://doi.org/10.1212/WNL.0000000000201654. - [30]
Zerres K, Rudnik-Schöneborn S, Forkert R, Wirth B. Genetic basis of adult-onset spinal muscular atrophy. Lancet (London, England). 1995; 346: 1162. https://doi.org/10.1016/s0140-6736(95)91835-3. - [31]
Russman BS. Spinal muscular atrophy: clinical classification and disease heterogeneity. Journal of Child Neurology. 2007; 22: 946–951. https://doi.org/10.1177/0883073807305673. - [32]
Gusset N, Stalens C, Stumpe E, Klouvi L, Mejat A, Ouillade MC, et al. Understanding European patient expectations towards current therapeutic development in spinal muscular atrophy. Neuromuscular Disorders: NMD. 2021; 31: 419–430. https://doi.org/10.1016/j.nmd.2021.01.012. - [33]
Cattinari M, Hervás D, Lemus M De, Tizzano E. Beyond the “walker” label: functional diversity and disease impact in spinal muscular atrophy patients with walking ability (P134). Neuromuscular Disorders: NMD. 2024; 43: 104441. https://doi.org/10.1016/j.nmd.2024.07.041. - [34]
Vázquez-Costa JF, Branas-Pampillón M, Medina-Cantillo J, Povedano M, Pitarch-Castellano I, López-Lobato M, et al. Validation of a Set of Instruments to Assess Patient- and Caregiver-Oriented Measurements in Spinal Muscular Atrophy: Results of the SMA-TOOL Study. Neurology and Therapy. 2023; 12: 89–105. https://doi.org/10.1007/s40120-022-00411-2. - [35]
Gómez-Andrés D, Martínez-Moreno M, Vázquez-Costa JF. Treatment of patients with spinal muscular atrophy 5q: Towards a new protocol. Neurologia. 2020; 36: 636–637. https://doi.org/10.1016/j.nrleng.2020.10.005. - [36]
AEMPS Agencia Española de Medicamentos y Productos Sanitarios. REEC - Registro Español de Estudios Clínicos n.d. 2022. Available at: https://reec.aemps.es/reec/public/list.html (Accedido: 26 de Julio de 2024). - [37]
Roche. Access to investigational medicines outside of a clinical trial n.d. 2020. Available at: https://www.roche.com/innovation/process/clinical-trials/investigational-medicines (Accedido: 13 de Enero de 2023). - [38]
FundAME. EL ACCESO AL USO COMPASIVO DEL MEDICAMENTO “SPINRAZA” PARA AFECTADOS DE AME TIPO 1 HA DADO COMIENZO EN ESPAÑA. 2017. Available at: https://www.fundame.net/el-acceso-al-uso-compasivo-del-medicamento-spinraza-para-afectados-de-ame-tipo-1-ha-dado-comienzo-en-espana-2/ (Accedido: 2 de Mayo de 2023).
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