Expanded access program with Nusinersen in SMA type I in Italy: Strengths and pitfalls of a successful experience

Messina, Sonia; Pane, Marika; Sansone, Valeria; Bruno, Claudio; Catteruccia, Michela; Vita, Giuseppe; Palermo, Concetta; Albamonte, Emilio; Pedemonte, Marina; Bertini, Enrico; Binetti, Luca; Mercuri, Eugenio; Lauro, Daniela; Pallara, Anita; Spinoglio, Simona; Solinas, Maria; Zappa, Grazia; Penno, Francesca; Ponzanelli, Cristina; Casiraghi, Jacopo; Villanova, Marcello; Tiziano, Danilo; Mandelli, Anna; Mastella, Chiara; Fontana, Alberto Mario; Ambrosini, Anna; Leone, Daniela; Sanctis, Roberto De; Forcina, Nicola; Piastra, Marco; Genovese, Orazio; Pedicelli, Alessandro; Sframeli, Maria; Versaci, A; Rulli, Imma; Gitto, Eloisa; Faraone, Cristina; Foresta, Stefania La; Macri, Maria Raquel; D’Amico, Adele; Colia, Giulia; Bonetti, Annamaria; Carlesi, Adelina; Cutrera, Renato; Chiarini, Maria Beatrice; Ferretti, Marta; Garaventa, Alberto; Montobbio, Giovanni; Gandolfo, Carlo; Iurilli, Valentina; Tacchetti, Paola; Bobeica, Emilia; D’Agostino, Alessia; Pirola, Alice; Luppone, Sara; Mattia, Elisa De; Falcier, Elisa; Rao, Fabrizio; Fedeli, Fausto; Mancini, Luca; Stoia, Paolo; Heinen, M; Cozzi, Valeria; Travaglia, Beatrice; Mizzotti, Emma

doi:10.1016/j.nmd.2017.09.006

Cited by 43 publications

(34 citation statements)

References 2 publications

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“…In 11 of the 24 patients, the procedure was performed using videofluorangiography ( n =2), computerized tomography ( n =4), or ultrasound ( n =5). There were no major side effects related to the injection, with only one adverse event related to severe bradycardia in an 8‐year‐old child …”

Section: Nusinersen and Expanded Access Programmementioning

confidence: 95%

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Nusinersen treatment of spinal muscular atrophy: current knowledge and existing gaps

Gidaro

Servais

2018

Develop Med Child Neuro

131

111

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Spinal muscular atrophy (SMA) is a recessive disorder caused by a mutation in the survival motor neuron 1 gene (SMN1); it affects 1 in 11 000 newborn infants. The most severe and most common form, type 1 SMA, is associated with early mortality in most cases and severe disability in survivors. Nusinersen, an antisense oligonucleotide, promotes production of full-length protein from the pseudogene SMN2. Nusinersen treatment prolongs survival of patients with type 1 SMA and allows motor milestone acquisition. Patients with type 2 SMA also show progress on different motor scales after nusinersen treatment. Nusinersen was recently approved by the European Medicines Agency and the US Food and Drug Administration; it is now reimbursed in several European countries and in the USA. In Australia, the transition from expanded access programme to commercial availability is coming soon. In New Zealand, an expanded access programme is opened, and in Canada price negotiation for the treatment is in progress. In this review we exemplify the clinical benefit of nusinersen in subgroups of patients with SMA. Nusinersen represents the first efficacious marked approved drug in type 1 and type 2 SMA. Different knowledge gaps, such as results in older patients, in patients with permanent ventilation, in patients with neonatal forms, or in patients after spinal fusion, still need to be addressed. WHAT THIS PAPER ADDS: Identifies gaps in knowledge about the efficacy of nusinersen in broader populations of patients with spinal muscular atrophy. Identifies open questions in populations of patients where proof of efficacy is available.

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Section: Nusinersen and Expanded Access Programmementioning

confidence: 95%

“…There were no major side effects related to the injection, with only one adverse event related to severe bradycardia in an 8-year-old child. 19 In France, 33 children older than 7 months were included in the expanded access programme. All patients continued the treatment after 6 months of observation.…”

Section: Nusinersen and Expanded Access Programmementioning

confidence: 99%

Nusinersen treatment of spinal muscular atrophy: current knowledge and existing gaps

Gidaro

Servais

2018

Develop Med Child Neuro

131

111

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“…The details of the EAP approach in Italy have already been reported. 3 As part of the EAP, before nusinersen became commercially available, the patients had access to the treatment only in the 5 Italian centers previously involved in nusinersen trials. The results of the first 6 months have recently been published.…”

Section: Methodsmentioning

confidence: 99%

“…The results of the first 6 months have recently been published. 3 Of the 104 SMA I patients followed up in the first 6 months of the EAP, 100 agreed to continue to be treated, whereas the other 4 decided to interrupt the treatment. Of the 4 who decided to interrupt the treatment in 2 it was because the results did not meet their expectations, in 1 because of the burden related to the procedure and of traveling, and in 1 because of the onset of a concomitant disease unrelated to SMA or to the treatment.…”

Section: Methodsmentioning

confidence: 99%

Nusinersen in type 1 spinal muscular atrophy: Twelve‐month real‐world data

Pane

Coratti

Sansone

et al. 2019

Annals of Neurology

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101

103

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Objective: The aim of the study was to report 12-month changes after treatment with nusinersen in a cohort of 85 type I spinal muscular atrophy patients of ages ranging from 2 months to 15 years and 11 months. Methods: All patients were assessed using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the Hammersmith Infant Neurological Examination-Section 2 (HINE-2). Results: Two of the 85 patients had 1 SMN2 copy, 61 had 2 copies, and 18 had 3 copies. In 4 patients the SMN2 copy number was not available. At baseline, the mean CHOP INTEND scores ranged between 0 and 52 (mean = 15.66, standard deviation [SD] = AE13.48), and the mean HINE-2 score was between 0 and 5 (mean = 0.69, SD = AE1.23). There was a difference between baseline and the 12-month scores on both the CHOP INTEND and the HINE-2 for the whole group (p < 0.001), the subgroups with 2 SMN2 copies (p < 0.001), and those with 3 SMN2 copies (p < 0.001). The difference was found not only in patients younger than 210 days at baseline (p < 0.001) but also in those younger than 5 years on the CHOP INTEND and younger than 2 years on the HINE-2. Interpretation: Our results, expanding the age range and the severity of type I patients treated with nusinersen over 1 year, provide additional data on the range of efficacy of the drug that will be helpful in making an informed decision on whether to start treatment in patients of different ages and severity.

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“…Now that nusinersen is approved and available either commercially or through expanded access programs, additional data are being obtained also in patients with more advanced disease. In Italy this has been done in a systematic manner [18] . The preliminary results suggest that for some older SMA patients, in an advanced stage of the disease, nusinersen treatment can have beneficial effects, such as resulting in achievement of better head control in a long term fully paralyzed patient, or less frequent need for aspiration.…”

Section: Collaborative Work Towards An Approved Therapy: the Example mentioning

confidence: 99%

Meeting report of the “Regulatory Exchange Matters” session at the 5th International TREAT-NMD Conference:

Aartsma‐Rus

Vroom

Balabanov

2018

Neuromuscular Disorders

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Expanded access program with Nusinersen in SMA type I in Italy: Strengths and pitfalls of a successful experience

Cited by 43 publications

References 2 publications

Nusinersen treatment of spinal muscular atrophy: current knowledge and existing gaps

Nusinersen treatment of spinal muscular atrophy: current knowledge and existing gaps

Nusinersen in type 1 spinal muscular atrophy: Twelve‐month real‐world data

Meeting report of the “Regulatory Exchange Matters” session at the 5th International TREAT-NMD Conference:

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