Nusinersen in adults with 5q-SMA newly eligible for reimbursement

Treatment of adult patients with 5q-associated spinal muscular atrophy type II and III with nusinersen will be reimbursed in Switzerland as of July 1, 2020. The costs are covered by the specialist list (SL) of the compulsory health insurance. This is a great relief for those affected; until now, a physician’s request for reimbursement in individual cases was the only possibility for reimbursement.

The high value of antisense oligonucleotide therapy with nusinersen for the treatment of 5q-associated spinal muscular atrophy (5q-SMA) in adult patients was recently supported by the publication of new study data in Lancet Neurology [1]. So far, only treatment with nusinersen (^Spinraza®) [2] of children and young adults with 5q-SMA up to 20 years of age has been reimbursed by the disability insurance (IV) in Switzerland. Adult patients had to hope for reimbursement on a case-by-case basis from the health insurance company. “For adult patients in Switzerland, the inclusion of ^Spinraza® in the list of specialties is therefore an important step,” says Katharina Gasser, MD, Managing Director of Biogen Switzerland AG. She continues, “The new data demonstrate that drug therapy in adult patients with 5q-SMA offers reasonable hope for stabilization or even improvement in their motor skills.” Excludes patients who are dependent on continuous ventilation or have the need for a permanent tracheostomy. Continuous ventilation is defined as 16 or more hours per day for 21 consecutive days without acute reversible infection. The Limitatio on ^Spinraza® can be viewed at the following link from the Federal Office of Public Health (FOPH): www.spezialitätenliste.ch.

Study data show clinically relevant improvements

The study, published in Lancet Neurology by Tim Hagenacker, MD, senior consultant, and Prof. Christoph Kleinschnitz, MD, director of the Department of Neurology at Essen University Hospital, and colleagues from nine other neuromuscular centers in Germany, includes data from a total of 124 patients with adult SMA (types 2 and 3). All patients received nusinersen according to the approved dosage of 12 mg per application. Of the 124 study participants, 57 patients were followed for a follow-up period of 14 months. Of the 20 female and 37 male patients with a mean age of 33 years (range: 16-59 years), 35% had SMA type 2, 65% had SMA type 3, and 40% were partially ambulatory. A majority of patients treated with nusinersen (^Spinraza®) showed clinically significant improvement and/or stabilization in common motor functions, which were maintained over time [2]. The results are based on the evaluation of several motor function scales such as HFMSE (Hammersmith Functional Motor Scale Expanded), RULM (Revised Upper Limb Module), and 6MWT (6-minute walk test). The HFMSE score (max 66 points) was on average 3.12 points higher in those treated with nusinersen. (A change in HFMSE ≥3 points is considered clinically significant). Improvement was greater in SMA type 3 than in SMA type 2 (4.2 vs. 1.1 points) and also greater in ambulatory than wheelchair-bound patients (4.6 vs. 2.1 points). Interestingly, the extent of the performance improvement was not dependent on the age of the patients or the duration of the disease. The median RULM score (max. 37 points) improved statistically significantly by 1.09 points. In the natural history of the disease, there is an annual worsening of 0.41 points [3]. Again, no dependence on the age of the patients was found. For the 6-minute walk test, the average clinically significant improvement after 14 months was 46 meters of walking distance. An improvement of ≥30 meters is considered clinically significant [4,5]. According to the study authors, the new results are consistent with those from a previous observational study [6]. Thus, there is increasing evidence that treatment with nusinersen (^Spinraza®) in adult patients with 5q-associated spinal muscular atrophy has comparable efficacy to that in infants and children with later SMA disease onset (types 2 and 3 SMA) in the randomized controlled phase III CHERISH development trial [7].

Spinal muscular atrophy

Spinal muscular atrophy (SMA) is a rare genetic disorder characterized by the loss of motor neurons in the spinal cord and lower brainstem [8–12]. The decline of motor neurons leads to severe, progressive weakness and atrophy of the dependent muscles. In the most severe form of SMA, there is paralysis and failure of muscle groups involved in basic life functions such as breathing or swallowing. In SMA, insufficient SMN (Survival of Motor Neuron) protein is produced due to a loss or defect of the SMN1 gene. This protein is central to the survival of motor neurons. The severity of SMA correlates with the remaining amount of SMN protein produced. Patients with infantile SMA, who have the highest need for intensive care and supportive care, make very little SMN protein. They never gain the ability to sit unassisted and only reach an age of more than two years with mechanical ventilation. Patients with later SMA disease onset produce greater amounts of the SMN protein. In them, the disease is less pronounced; they lose the motor milestones already acquired during their lives, which has a profound impact on their lives.

Source: Biogen

Literature:

1. Hagenacker T, et al: Nusinersen in adults with 5q spinal muscular atrophy: a non-interventional, multicentre, observational cohort study. Lancet Neurology 2020; 19(4): 317-325.
2. Spinraza® technical ^information, as of August 2019; www.swissmedicinfo.ch
3. Mazzone E, et al: Revised upper limb module for spinal muscular atrophy: development of a new module. Muscle Nerve 2017; 55(6): 869-874.
4. Young SD, et al: Six-minute Walk Test Is Reliable and Valid in Spinal Muscular Atrophy. Muscle Nerve 2016; 54(5): 836-842.
5. Montes J, et al: Six-minute walk test demonstrates motor fatigue in spinal muscular atrophy. Neurol 2010; 74: 833-838.
6. Walter MC, et al: Safety and treatment effects of nusinersen in longstanding adult 5q-SMA type 3 – a prospective observational study. J Neuromuscul Dis 2019; 6: 453-465.
7. Mercuri E, et al: Nusinersen versus sham control in later-onset spinal muscular atrophy. N Engl J Med 2018; 378: 625-635.
8. Darras B, et al: Spinal Muscular Atrophies. In: Vivo BTD (ed.): Neuromuscular Disorders of Infancy, Childhood, and Adolescence (2nd ed.). San Diego: Academic Press; 2015; 117-145.
9. Lefebvre S, et al: Identification and Characterization of a Spinal Muscular Atrophy-Determining Gene. Cell 1995; 80(1): 155-165.
10. Mailman MD, et al: Molecular Analysis of Spinal Muscular Atrophy and Modification of the Phenotype by SMN2. Genet Med 2002; 4(1): 20-26.
11. Monani UR, et al: A Single Nucleotide Difference That Alters Splicing Patterns Distinguishes the SMA Gene SMN1 From the Copy Gene SMN2. Hum Mol Genet 1999; 8(7): 1177-1183.
12. Peeters K, et al: Clinical and genetic diversity of SMN1-negative proximal spinal muscular atrophies. Brain 2014; 137(Pt 11): 2879-2896.

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