Section 16
Neuromuscular & Gene Therapy
SMA, Duchenne & Antisense Therapies
16 AGENTS
Nusinersen
SpinrazaAntisense oligonucleotide
- Forms
- Intrathecal: 12mg/5mL (2.4mg/mL) vial
- Dose
- Label (rev 3/2026) has two regimens: LOW DOSE 12mg x4 loading (first 3 at 14-day intervals, 4th 30 days after the 3rd), then 12mg every 4 months | HIGH DOSE two 50mg loading doses 14 days apart, then 28mg every 4 months starting 4 months after last loading dose
- MOA
- Modifies SMN2 splicing to ↑functional SMN protein
Risdiplam
EvrysdiSMN2 splicing modifier
- Forms
- Powder for oral solution: 60mg (0.75mg/mL after constitution) | Tab: 5mg
- Dose
- Once daily: under 2 months 0.15mg/kg | 2 months to <2 years 0.2mg/kg | 2 years+ under 20kg 0.25mg/kg | 2 years+ 20kg or more 5mg
- MOA
- Small molecule that ↑functional SMN protein
Onasemnogene abeparvovec (IV)
ZolgensmaAAV9 gene therapy
- Forms
- IV: single-dose weight-based kit
- Dose
- One-time IV infusion, 1.1 x 10^14 vg/kg (age under 2); BOXED WARNING: serious liver injury
- MOA
- Delivers a functional SMN1 gene
Onasemnogene abeparvovec (intrathecal)
ItvismaAAV9 gene therapy
- Forms
- Intrathecal: 1.2 x 10^14 vg per 3mL vial
- Dose
- One-time fixed dose 1.2 x 10^14 vg intrathecal bolus over 1-2 min (age 2+); BOXED WARNING: serious liver injury; not for patients previously treated with Zolgensma
- MOA
- Delivers a functional SMN1 gene
Deflazacort
EmflazaCorticosteroid
- Forms
- Tab: 6, 18, 30, 36mg | Susp: 22.75mg/mL
- Dose
- About 0.9mg/kg once daily (DMD, age 2+); reduce dose with moderate/strong CYP3A4 inhibitors
- MOA
- Anti-inflammatory/immunosuppressive
Vamorolone
AgamreeDissociative steroid
- Forms
- Oral susp: 40mg/mL
- Dose
- Weight-based once daily, approx 6mg/kg/day (DMD, age 2+)
- MOA
- Glucocorticoid/mineralocorticoid receptor modulation with reduced transactivation
Givinostat
DuvyzatHDAC inhibitor
- Forms
- Oral suspension (weight-based dosing)
- Dose
- Weight-based BID with food (DMD, age 6+)
- MOA
- Inhibits histone deacetylases, ↓muscle inflammation and fibrosis
Eteplirsen
Exondys 51Antisense oligonucleotide (PMO)
- Forms
- IV: 50mg/mL single-dose vials
- Dose
- 30mg/kg IV once weekly (exon 51 amenable DMD; accelerated approval)
- MOA
- Skips dystrophin exon 51
Golodirsen
Vyondys 53Antisense oligonucleotide (PMO)
- Forms
- IV: 50mg/mL single-dose vials
- Dose
- 30mg/kg IV once weekly (exon 53 amenable DMD; accelerated approval)
- MOA
- Skips dystrophin exon 53
Casimersen
Amondys 45Antisense oligonucleotide (PMO)
- Forms
- IV: 50mg/mL single-dose vials
- Dose
- 30mg/kg IV once weekly (exon 45 amenable DMD; accelerated approval)
- MOA
- Skips dystrophin exon 45
Viltolarsen
ViltepsoAntisense oligonucleotide
- Forms
- IV: 250mg/5mL (50mg/mL) vials
- Dose
- 80mg/kg IV once weekly (exon 53 amenable DMD; accelerated approval)
- MOA
- Skips dystrophin exon 53
Delandistrogene moxeparvovec
ElevidysAAVrh74 gene therapy
- Forms
- IV: single-dose weight-based kit
- Dose
- One-time weight-based IV infusion; BOXED WARNING acute liver injury/failure; ambulatory patients age 4+ only; contraindicated with DMD exon 8 and/or 9 deletions
- MOA
- Delivers a micro-dystrophin gene
Dichlorphenamide
Keveyis / OrmalviCarbonic anhydrase inhibitor
- Forms
- Tab: 50mg
- Dose
- Periodic paralysis: start 50mg once or twice daily, titrate weekly; range 50-200mg/day; reassess at 2 months
- MOA
- Mild metabolic acidosis and kaliuresis; exact mechanism in periodic paralysis uncertain
Alglucosidase alfa
LumizymeEnzyme replacement (GAA)
- Forms
- IV: 50mg vial
- Dose
- Pompe disease: 20mg/kg IV every 2 weeks
- MOA
- Replaces acid alpha-glucosidase to degrade lysosomal glycogen
Avalglucosidase alfa
NexviazymeEnzyme replacement (GAA)
- Forms
- IV: 100mg vial
- Dose
- Pompe disease: 20mg/kg IV every 2 weeks (40mg/kg if under 30kg)
- MOA
- Replaces acid alpha-glucosidase with enhanced M6P targeting
Cipaglucosidase alfa + miglustat
Pombiliti + OpfoldaEnzyme replacement + enzyme stabilizer
- Forms
- IV: 105mg vial (Pombiliti) | Cap: 65mg (Opfolda)
- Dose
- Late-onset Pompe, adults 40kg+: 20mg/kg IV every 2 weeks (about 4h) with Opfolda 260mg (50kg+) or 195mg (40 to <50kg) orally
- MOA
- Replaces GAA; miglustat stabilizes the enzyme in blood