Drug information of Golodirsen


Golodirsen is a morpholino antisense oligomer designed to treat about 8% of patients with Duchenne Muscular Dystrophy (DMD). This is an X-linked condition leading to progressive muscle degeneration that begins in early childhood, rendering many patients wheelchair-bound by age 12. Often, patients succumb to this condition by age 30 or younger due to cardiac and respiratory complications. A similar drug used in the treatment of other types of DMD is eteplirsen, which targets a different genetic mutation
Golodirsen is indicated to treat Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation of the DMD gene that would benefit from exon 53 skipping. Continued FDA approval of this drug is contingent upon the results of clinical trials to confirm its benefit

:Dosage Forms & Strengths
Injection, Concentrated Solution: 100mg/2mL (50mg/mL) single-dose vial

Mechanism of effect

The hallmark of Duchenne Muscular Dystrophy is the absence of the important muscle stabilizing protein, dystrophin, that is caused by a deletion mutation on the DMD (dystrophin) gene. This results in the production of a non-functional protein. Lack of dystrophin protein leads to progressive muscle weakness and degeneration

Golodirsen binds to exon 53 of dystrophin pre-mRNA on the DMD gene, excluding this protein coding unit during mRNA processing. The exclusion (or skipping) of exon 53 by golodirsen has the end result of changing out-of-frame mRNA to in-frame mRNA, inducing the production of dystrophin. The production of an imperfect dystrophin protein induced by golodirsen likely leads to a less severe condition, Becker Muscular Dystrophy (BMD), characterized by the production of a truncated dystrophin protein. Patients with BMD generally can expect a longer lifespan and improved quality of life


Golodirsen masks genetic mutations that result in a cascade of events which treat Duchenne Muscular Dystrophy in about 8% of patients. Golodirsen indirectly induces the production of dystrophin, an important protein for muscle function. It is not yet confirmed whether motor function is improved by golodirsen, however, clinical trials are underway to examine its clinical benefits

:A note on Nephrotoxicity
Though clinical trials have not yet confirmed that golodirsen is nephrotoxic, other morpholino antisense oligonucleotides have been known to cause nephrotoxicity. Ensure to monitor renal function during golodirsen therapy


Systemic exposure increases proportionally with dose, with minimal accumulation

Protein bound:33-39%
Vd: 668 mL/kg

Metabolically stable; no metabolites detected in plasma or urine

Half-life: 3.4 hr
Plasma clearance: 346 mL/hr/kg
Mostly excreted unchanged in urine


30mg/kg IV qWeek

:Renal Impairment

Renal clearance is reduced in non-DMD adults with renal impairment, based on estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet and Renal Disease (MDRD) equation
No specific dosage adjustment can be recommended for patients with DMD who have renal impairment based on eGFR
Closely monitor patients with known renal function impairment during treatment

:Dosing Considerations
Measure GFR before initiating
Monitoring for renal toxicity during treatment is recommended


Hypersensitivity reactions, including rash, pyrexia, pruritus, urticaria, dermatitis, and skin exfoliation, reported, some requiring treatment
If a hypersensitivity reaction occurs, institute appropriate medical treatment and consider slowing the infusion or interrupting therapy

:Renal Toxicity
Renal toxicity was observed in animals
Although renal toxicity was not observed in the clinical studies, renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides
Monitor renal function during therapy
Because of the effect of reduced skeletal muscle mass on creatinine measurements, serum creatinine may not be a reliable measure of renal function in patients with DMD
Measure GFR by 24-hr urine collection before initiating therapy
Monthly monitoring for proteinuria by dipstick urinalysis and monitoring of serum cystatin C q3Months is recommended
If confirmed dipstick proteinuria of 2+ or greater or elevated serum cystatin C, a 24-hr urine collection to quantify proteinuria and assess GFR should be performed

Points of recommendation

:IV Preparation
Preservative-free concentrated solution that requires dilution before administration
Inspect vials visually for particulate matter and discoloration; solution should appear as a clear to slightly opalescent, colorless liquid
Use aseptic technique
Allow vials to warm to room temperature
Gently invert vials to mix contents; do not shake
Withdraw calculated dose from vial(s) and dilute in 0.9% NaCl for a total volume of 100-150 mL; gently invert 2-3 times to mix; do not shake
Visually inspect diluted solution for particulates
Administer immediately after dilution; complete infusion within 4 hr of dilution

:IV Administration
Consider topical anesthetic cream application to the infusion site before administration
Flush IV access line with 0.9% NaCl before and after infusion
Infuse IV over 35-60 minutes
Do not mix with other medication or infuse other medication concomitantly vial same IV access line
Missed dose: May be administered as soon as possible after the scheduled dose

:Adverse Effects
Headache, Pyrexia, Fall, Abdominal pain, Nasopharyngitis, Cough, Vomiting, Nausea, Administration site pain, Back pain, Pain, Diarrhea, Dizziness, Ligament sprain, Contusion, Influenza, Oropharyngeal pain, Rhinitis, Skin abrasion, Ear infection, Seasonal allergy, Tachycardia, Catheter site-related reaction, Constipation, Fracture, Hypersensitivity

Pregnancy level

No human or animal data are available to assess use during pregnancy

Breast feeding warning

No human or animal data are available to assess effects on milk production, presence in milk, or effects on the breastfed infant

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