Golodirsen
Golodirsen Uses, Dosage, Side Effects, Food Interaction and all others data.
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 was developed by Sarepta Therapeutics and granted accelerated FDA approval on December 12, 2019 due to the urgent need for this drug in patients suffering from a certain form of DMD. Continued approval of this drug will depend on the results of clinical trials that confirm its clinical benefit. Golodirsen was initially rejected for FDA approval over concerns about its potential renal toxicity, however, clinical trials did not show significant toxicity.
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.
| Trade Name | Golodirsen |
| Availability | Prescription only |
| Generic | Golodirsen |
| Golodirsen Other Names | Golodirsen |
| Related Drugs | deflazacort, Emflaza, Exondys 51, Amondys 45, Vyondys 53, eteplirsen |
| Weight | 50mg/ml, |
| Type | Intravenous Solution, Intravenous |
| Protein binding | The protein binding of golodirsen ranges from 33 to 39%. |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Golodirsen is a drug used to treat certain mutations that cause Duchenne muscular dystrophy (DMD).
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.
Golodirsen is also used to associated treatment for these conditions: Duchenne's Muscular Dystrophy (DMD)
How Golodirsen works
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.
Toxicity
No overdose information is available, however, renal toxicity has been seen with the administration of antisense oligomers, sometimes resulting in fatal glomerulonephritis. In the case of an overdose, it is advisable to provide supportive care and monitor renal function. LD50 information is currently unavailable for this drug.
Food Interaction
No interactions found.Golodirsen Disease Interaction
Volume of Distribution
The volume of distribution at steady-state is approximately 668 mL/kg at 30 mL/kg dose of golodirsen.
Elimination Route
This drug is given by the intravenous route, and is likely rapidly absorbed into the circulation. Pharmacokinetic studies for eteplirsen determined that Cmax occur within 1.1 to 1.2 hours of infusion initiation, after the administration of doses ranging from 0.5 mg/kg/week to 50 mg/kg/week.
Half Life
In a pharmacokinetic study, the elimination half-life of golodirsen was 3.4 hours with a standard deviation of 0.6 hours.
Clearance
This drug is rapidly cleared from the systemic circulation, like other members of its drug class. The total clearance of eteplirsen, a drug from the same class, was 339 mL/h/kg after regular doses of 30 mg/kg/week. The clearance of golodirsen is likely similar.
Elimination Route
Golodirsen is excreted primarily as unchanged drug in the urine.
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