Putting our best foot forward: Clinical, treatment‐based and ethical considerations of nusinersen therapy in Canada for spinal muscular atrophy

Abstract

Spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality. SMA is a spectral disorder and is categorised based on symptom onset and severity. The median life expectancy for infants with SMA presenting before 6 months of age is less than 2 years without respiratory support. To date, there is no cure for SMA. In June 2017, nusinersen was approved in Canada as the first disease-modifying drug for SMA because of its demonstrated benefits on motor function and survival in clinical trials. However, with a price tag of almost 1 million dollars for the first year of therapy, careful clinical, treatment-based and ethical consideration of the principles of (i) best interests; (ii) universality; (iii) portability; (iv) public administration; (v) accessibility; and (vi) comprehensiveness are important guideposts to ensure transparent and equitable allocation of health-care resources for nusinersen and all other future orphan drugs.Nusinersen is a modified antisense oligonucleotide that prevents nucleases from binding at a specific sequence on SMN2 premessenger RNA, thus promoting exon retention. More specifically, exon 7 of the SMN2 pre-messenger RNA is retained. As a result, full-length, functional SMN protein is produced. 5,6

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

“…23,24 In our experience, <7.5% of the initial cohort left the program, 4.1% immediately after they started and only 3.3% in the follow-up. Following the commercial availability of nusinersen, there has been discussion on whether such small changes observed in some patients justify the cost of the drug or the effort for the patient and the family to undergo repeated intrathecal procedures and frequent multiple visits to the hospital.…”

“…Following the commercial availability of nusinersen, there has been discussion on whether such small changes observed in some patients justify the cost of the drug or the effort for the patient and the family to undergo repeated intrathecal procedures and frequent multiple visits to the hospital. 23,24 In our experience, <7.5% of the initial cohort left the program, 4.1% immediately after they started and only 3.3% in the follow-up. Using a patient-reported questionnaire to investigate if they felt there was a functional improvement that was clinically meaningful to them, 73.61% of the responders who completed the questionnaire felt that there had been an improvement that was mainly related to motor function.…”

“…Unfortunately, at the time the EAP started, because of limited funding and the large number of patients followed in each center, it was not feasible to consistently perform compound muscle action potential or motor unit number estimation to have objective measurements of the residual motoneuron activity at baseline and possible changes over time, or to use recent biomarkers like phosphorylated neurofilament heavy chain that may have helped to better understand the mechanisms underlying the changes observed in our cohort. Following the commercial availability of nusinersen, there has been discussion on whether such small changes observed in some patients justify the cost of the drug or the effort for the patient and the family to undergo repeated intrathecal procedures and frequent multiple visits to the hospital …”

Palliative Care in SMA Type 1: A Prospective Multicenter French Study Based on Parents' Reports

“…This need for standardization of care has been claimed (30) to ensure better controlled studied and further analysis, especially concerning nusinersen, which remains a new drug, with lacking evidence on its long-term efficacy and tolerance profile. Moreover, major issues concerning medico-economic evaluation of orphan drugs emerge (31)(32)(33)(34), not only of the drug itself but also of the medical organization needed to ensure appropriate deliverance and monitoring, prolonged life with potential prolonged need for technical care (enteral nutrition, respiratory support, orthopedic installation, etc.) (35,36), or, on the contrary, improvement of respiratory function with less hospitalizations, for instance (37).…”

Do we always need to treat patients with spinal muscular atrophy? A personal view and experience

“…Furthermore, the anxiety and distress caused by the life-long administration of a burdensome procedure, associated with the frustration due to the lack of perceived improvements, can have a major impact on the child and family's quality of life. Last, the cost of the drug and of the hospital admissions should be considered [9,10].…”