Cost Effectiveness of Nusinersen in the Treatment of Patients with Infantile-Onset and Later-Onset Spinal Muscular Atrophy in Sweden

Abstract

Background Spinal muscular atrophy is a rare neuromuscular disorder with a spectrum of severity related to age at onset and the number of SMN2 gene copies. Infantile-onset (≤ 6 months of age) is the most severe spinal muscular atrophy and is the leading monogenetic cause of infant mortality; patients with later-onset (> 6 months of age) spinal muscular atrophy can survive into adulthood. Nusinersen is a new treatment for spinal muscular atrophy. Objective The objective of this study was to evaluate the cost effectiveness of nusinersen for the treatment of patients with infantile-onset spinal muscular atrophy and later-onset spinal muscular atrophy in Sweden. Methods One Markov cohort health-state transition model was developed for each population. The infantile-onset and later-onset models were based on the efficacy results from the ENDEAR phase III trial and the CHERISH phase III trial, respectively. The cost effectiveness of nusinersen in both models was compared with standard of care in Sweden. Results For a time horizon of 40 years in the infantile-onset model and 80 years in the later-onset model, treatment with nusinersen resulted in 3.86 and 9.54 patient incremental quality-adjusted life-years and 0.02 and 2.39 caregiver incremental quality-adjusted life-years and an incremental cost of 21.9 and 38.0 million SEK (Swedish krona), respectively. These results translated into incremental cost-effectiveness ratios (including caregiver quality-adjusted life-years) of 5.64 million SEK (€551,300) and 3.19 million SEK (€311,800) per quality-adjusted life-year gained in the infantile-onset model and later-onset model, respectively. Conclusions Treatment with nusinersen resulted in overall survival and quality-adjusted life-year benefits but with incremental costs above 21 million SEK (€2 million) [mainly associated with maintenance treatment with nusinersen over a patient's lifespan]. Nusinersen was not cost effective when using a willingness-to-pay threshold of 2 million SEK (€195,600), which has been considered in a recent discussion by the Dental and Pharmaceutical Benefits Agency as a reasonable threshold for rare disease. Nonetheless, nusinersen gained reimbursement in Sweden in 2017 for paediatric patients (below 18 years old) with spinal muscular atrophy type I-IIIa.

<p>Clinical Evidence Supporting Early Treatment Of Patients With Spinal Muscular Atrophy: Current Perspectives</p>

“…By increasing the life expectancy of these patients, the cost related to their disability will dramatically increase resulting in a negative cost-to-effectiveness evaluation. For example, nusinersen treatment provides overall benefits in terms of adjusted survival and quality of life per year, both for patients and their caregivers 39. However, with additional costs in excess of $2.4 million,39 mainly associated with maintenance treatment over the lifetime of the patient, and frequent hospitalization for respiratory events,40 this is not considered a cost-effective threshold, even for a rare disease.…”

“…For example, nusinersen treatment provides overall benefits in terms of adjusted survival and quality of life per year, both for patients and their caregivers 39. However, with additional costs in excess of $2.4 million,39 mainly associated with maintenance treatment over the lifetime of the patient, and frequent hospitalization for respiratory events,40 this is not considered a cost-effective threshold, even for a rare disease. Obtaining a much better efficacy from the same drug by initiating the treatment earlier has the potential to improve this ratio sufficiently to make treatment worthwhile.…”

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

“…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). In that context, not only medical costs are taken into account but also social costs for families since one parent usually needs to reduce or discontinue external employment (38).…”

Cost effectiveness of nusinersen for patients with infantile-onset spinal muscular atrophy in US

“…The cost-utility model was developed from a societal perspective, with a health care perspective analysis undertaken as a scenario, using a 40 year time horizon. [27] That model structure was also similar to the manufacturer-submitted models to NICE, CADTH, and other HTA agencies, with changes mainly to the patient utilities used and costs to match the respective jurisdiction. In our model, the incremental cost-effectiveness ratio was approximately $1.1 million per QALY while the corresponding results were substantially more favorable in the manufacturer-funded model, at approximately SEK 5.6 million ($623,000) per QALY.…”