Zolgensma

Gene therapy for 5q spinal muscular atrophy (SMA) in patients w/ bi-allelic mutation in SMN1 gene & clinical diagnosis of SMA Type 1, or patients w/ bi-allelic mutation in SMN1 gene & up to 3 copies of SMN2 gene.

IV Single dose slowly infused over approx 60 min. Patient weighing 20.6-21 kg Recommended dose: 2.31 x 10¹⁵ vector genomes (vg). Total vol: 115.5 mL, 20.1-20.5 kg Recommended dose: 2.26 x 10¹⁵ vg. Total vol: 112.8 mL, 19.6-20 kg Recommended dose: 2.2 x 10¹⁵ vg. Total vol: 110 mL, 19.1-19.5 kg Recommended dose: 2.15 x 10¹⁵ vg. Total vol: 107.3 mL, 18.6-19 kg Recommended dose: 2.09 x 10¹⁵ vg. Total vol: 104.5 mL, 18.1-18.5 kg Recommended dose: 2.04 x 10¹⁵ vg. Total vol: 101.8 mL, 17.6-18 kg Recommended dose: 1.98 x 10¹⁵ vg. Total vol: 99 mL, 17.1-17.5 kg Recommended dose: 1.93 x 10¹⁵ vg. Total vol: 96.3 mL, 16.6-17 kg Recommended dose: 1.87 x 10¹⁵ vg. Total vol: 93.5 mL, 16.1-16.5 kg Recommended dose: 1.82 x 10¹⁵ vg. Total vol: 90.8 mL, 15.6-16 kg Recommended dose: 1.76 x 10¹⁵ vg. Total vol: 88 mL, 15.1-15.5 kg Recommended dose: 1.71 x 10¹⁵ vg. Total vol: 85.3 mL, 14.6-15 kg Recommended dose: 1.65 x 10¹⁵ vg. Total vol: 82.5 mL, 14.1-14.5 kg Recommended dose: 1.6 x 10¹⁵ vg. Total vol: 79.8 mL, 13.6-14 kg Recommended dose: 1.54 x 10¹⁵ vg. Total vol: 77 mL, 13.1-13.5 kg Recommended dose: 1.49 x 10¹⁵ vg. Total vol: 74.3 mL, 12.6-13 kg Recommended dose: 1.43 x 10¹⁵ vg. Total vol: 71.5 mL, 12.1-12.5 kg Recommended dose: 1.38 x 10¹⁵ vg. Total vol: 68.8 mL, 11.6-12 kg Recommended dose: 1.32 x 10¹⁵ vg. Total vol: 66 mL, 11.1-11.5 kg Recommended dose: 1.27 x 10¹⁵ vg. Total vol: 63.3 mL, 10.6-11 kg Recommended dose: 1.21 x 10¹⁵ vg. Total vol: 60.5 mL, 10.1-10.5 kg Recommended dose: 1.16 x 10¹⁵ vg. Total vol: 57.8 mL, 9.6-10 kg Recommended dose: 1.1 x 10¹⁵ vg. Total vol: 55 mL, 9.1-9.5 kg Recommended dose: 1.05 x 10¹⁵ vg. Total vol: 52.3 mL, 8.6-9 kg Recommended dose: 9.9 x 10¹⁴ vg. Total vol: 49.5 mL, 8.1-8.5 kg Recommended dose: 9.4 x 10¹⁴ vg. Total vol: 46.8 mL, 7.6-8 kg Recommended dose: 8.8 x 10¹⁴ vg. Total vol: 44 mL, 7.1-7.5 kg Recommended dose: 8.3 x 10¹⁴ vg. Total vol: 41.3 mL, 6.6-7 kg Recommended dose: 7.7 x 10¹⁴ vg. Total vol: 38.5 mL, 6.1-6.5 kg Recommended dose: 7.2 x 10¹⁴ vg. Total vol: 35.8 mL, 5.6-6 kg Recommended dose: 6.6 x 10¹⁴ vg. Total vol: 33 mL, 5.1-5.5 kg Recommended dose: 6.1 x 10¹⁴ vg. Total vol: 30.3 mL, 4.6-5 kg Recommended dose: 5.5 x 10¹⁴ vg. Total vol: 27.5 mL, 4.1-4.5 kg Recommended dose: 5 x 10¹⁴ vg. Total vol: 24.8 mL, 3.6-4 kg Recommended dose: 4.4 x 10¹⁴ vg. Total vol: 22 mL, 3.1-3.5 kg Recommended dose: 3.9 x 10¹⁴ vg. Total vol: 19.3 mL, 2.6-3 kg Recommended dose: 3.3 x 10¹⁴ vg. Total vol: 16.5 mL.

Hypersensitivity.

Do not administer as IV push or bolus. Baseline lab testing is required prior to infusion, including AAV9 Ab testing (using an appropriately validated assay), liver function (ALT, AST, total bilirubin, albumin, prothrombin time, partial thromboplastin time, & INR), creatinine, CBC (including Hb & platelet count), & troponin-I. Risk of immune-mediated hepatotoxicity; thrombocytopenia; increased cardiac troponin-I levels. Reports of acute serious liver injury & acute liver failure typically w/in 2 mth after infusion & despite receiving corticosteroids before & after infusion. Reports of thrombotic microangiopathy occurring w/in the 1st 2 wk after infusion. Immune response to AAV9 capsid will occur after infusion. Immunomodulation w/ corticosteroids is recommended. Check for signs & symptoms of active infectious disease prior to initiation of immunomodulatory regimen & prior to administration of onasemnogene abeparvovec. Do not initiate treatment concurrently to active infections (acute or uncontrolled chronic) until infection has resolved & patient is clinically stable. Adjust vaccination schedule to accommodate concomitant corticosteroid administration prior to & following onasemnogene abeparvovec infusion. Theoretical risk of tumourigenicity due to integration of AAV vector DNA into the genome. Temporary shedding occurs, primarily through bodily waste. Patients on treatment should not donate blood, organs, tissues or cells for transplantation. Contains 4.6 mg Na per mL. The benefit/risk profile is not established in patients w/ advanced SMA, kept alive through permanent ventilation & w/o the ability to thrive. Carefully consider risks & benefits of therapy in patients w/ pre-existing hepatic impairment. Caution in patients w/ ALT, AST, total bilirubin levels (except due to neonatal jaundice) >2 x ULN or +ve serology for hepatitis B or C; bi-allelic mutation of SMN1 gene & only 1 copy of SMN2; baseline anti-AAV9 Ab titres >1:50. Safety & efficacy have not been established in patients w/ renal impairment; premature neonates before reaching full-term gestational age; ped patients ≥2 yr or weighing >13.5 kg.

Increased hepatic enzyme. Thrombocytopenia; vomiting; hepatotoxicity; pyrexia; increased troponin.

Safety has not been established in patients receiving hepatotoxic medicinal products or using hepatotoxic substances. Limited experience w/ use of concomitant 5q SMA targeting agents.

Other Drugs Acting on Musculo-Skeletal System

M09AX09 - onasemnogene abeparvovec ; Belongs to the class of other drugs for disorders of the musculo-skeletal system.

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