Short-term safety results from compassionate use of risdiplam in patients with spinal muscular atrophy in Germany (vol 17, 276, 2022)

被引：2

作者：

Hahn, Andreas ^{[1
]}

Guenther, Rene ^{[2
]}

Ludolph, Albert ^{[3
]}

Schwartz, Oliver ^{[4
]}

Trollmann, Regina ^{[5
]}

Weydt, Patrick ^{[6
]}

Weiler, Markus ^{[7
]}

Neuland, Kathrin ^{[8
]}

Schwaderer, Martin Sebastian ^{[8
]}

Hagenacker, Tim ^{[9
]}

机构：

[1] Univ Giessen, Dept Child Neurol, Giessen, Germany

[2] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Neurol, Dresden, Germany

[3] Univ Ulm, Dept Neurol, Ulm, Germany

[4] Munster Univ Hosp, Dept Pediat Neurol, Munster, Germany

[5] Friedrich Alexander Univ Erlangen Nurnberg, Div Pediat Neurol, Dept Pediat, Erlangen, Germany

[6] Univ Bonn, Dept Neurodegenerat Dis & Gerontopsychiat Neurol, Med Ctr, Bonn, Germany

[7] Heidelberg Univ Hosp, Dept Neurol, Heidelberg, Germany

[8] Roche Pharma AG, Grenzach Wyhlen, Germany

[9] Univ Hosp Essen, Dept Neurol, Essen, Germany

来源：

ORPHANET JOURNAL OF RARE DISEASES | 2022年 / 17卷 / 01期

关键词：

Compassionate use; Real-world data; Risdiplam; Spinal muscular atrophy; Splicing modifier; Survival of motor neuron 1 protein;

D O I：

10.1186/s13023-022-02548-7

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background: The oral, selective SMN2-splicing modifier risdiplam obtained European approval in March 2021 for the treatment of patients ≥ 2 months old with a clinical diagnosis of 5q-associated spinal muscular atrophy (SMA) 1/2/3 or with 1–4 SMN2 gene copies. For the preceding 12 months, this compassionate use program (CUP) made risdiplam available to patients with SMA1/2 in Germany who could not receive any approved SMA therapy. Patients and methods: Patients with SMA1/2, aged ≥ 2 months at enrollment, could be included if they were not eligible for, no longer responsive to, or not able to tolerate nusinersen or not able to receive onasemnogene abeparvovec. Oral risdiplam dosing ranged from 0.2 mg/kg to 5 mg depending on age and weight. All treatment decisions were made by the attending physicians, who were required to report all adverse events (AEs). Results: Between March 12, 2020 and March 30, 2021, 36 patients with SMA1 and 98 patients with SMA2 were enrolled, with 31 patients and 80 patients receiving ≥ 1 risdiplam dose, respectively. The median (range) age was 10.5 (3–52) years in the SMA1 cohort, and 26.5 (3–60) years in the SMA2 cohort. 22.2% of patients with SMA1 and 48.0% with SMA2 were treatment-naïve. Most patients were not eligible/could not continue to receive nusinersen due to scoliosis/safety risk (SMA1: 75.0%; SMA2: 96.9%), risks associated with sedation (77.8%; 63.3%), or loss of efficacy (30.6%; 12.2%). Safety data were generally in line with the safety profile of risdiplam in ongoing clinical studies. Gastrointestinal disorders were the most common AEs. For patients with SMA1, 30 AEs were reported in 13 cases with 2 serious AEs in 1 patient. For SMA2, 100 AEs were documented in 31 case reports, including 8 serious AEs in 2 patients. Conclusions: We present the first real-world safety data of risdiplam in patients with SMA in Germany. Our observations indicated no new safety signals under real-world conditions. Real-world SMA1/2 populations comprise considerable numbers of patients who are not eligible for gene therapy and cannot tolerate or have failed nusinersen treatment. This medical need may be addressed by oral risdiplam. © 2022, The Author(s).

引用

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