Golodirsen

Golodirsen is used to treat Duchenne muscular dystrophy (DMD) in children and young adults with a confirmed mutation of the DMD gene that is amenable to exon 53 skipping. It is an exon-skipping treatment given 1 time a week via an intravenous infusion by a healthcare provider.

• Your healthcare provider will conduct a genetic test to identify if you or your child is one of the estimated 8% of people with DMD who are suitable for treatment with golodirsen.

Golodirsen (golodirsen) gained FDA approval on December 12, 2019, under the accelerated approval designation. The brand name is Vyondys 53 (often shortened to Vyondys).

• Continued approval may be contingent upon verification of a clinical benefit in clinical trials.

Golodirsen's mechanism of action uses exon-skipping technology to skip over exon 53, which allows the body to make a shorter form of a protein called dystrophin, needed for muscle integrity. People with DMD have a genetic mutation in the gene that encodes for this protein, which means they cannot produce enough, or any, working copies of this protein. Without this protein, muscle cells become damaged and weaken with time.

By skipping over exon 53, golodirsen allows different exons to join together to produce a dystrophin protein that is shorter but has some function. Clinical trials report exon-skipping as confirmed by muscle biopsy in 25 of 25 study participants. After 48 weeks of treatment, participants showed an average increase of nearly 16 times their baseline level of dystrophin.

Golodirsen belongs to the drug class called antisense oligonucleotides.

Golodirsen is administered as an IV infusion (an infusion into your vein) 1 time a week by a healthcare provider.

• They may apply a topical anesthetic cream to the site where the infusion will be administered, if needed, to help numb the area.
• Golodirsen must be given slowly, and the infusion can take 35 to 60 minutes to complete.

Hypersensitivity reactions can occur when golodirsen is administered. If this happens, then the infusion may need to be slowed or interrupted.

Your kidney function may need to be checked while receiving treatment with golodirsen.

Before receiving golodirsen, tell your healthcare provider if you:

• have or have had kidney problems
• have had an allergic reaction to golodirsen, Vyondys, Vyondys 53, or any of the inactive ingredients in the injection
• are pregnant or intending to become pregnant
• are breastfeeding or intend to breastfeed.

The most common side effects of golodirsen are:

• headache
• fever
• fall
• abdominal pain
• nose or throat infection
• cough
• vomiting
• nausea.

Other common side effects of golodirsen include:

• pain at the injection site or reactions related to the IV catheter site
• back pain, mouth or throat pain, or general pain
• diarrhea or constipation
• dizziness
• flu, stuffy/runny nose, ear infections, seasonal allergies
• bruising, skin scratches or scrapes, ligament stretches or tears, broken bones
• fast heartbeat.

Serious side effects and warnings

Golodirsen can cause the following serious side effects:

• Hypersensitivity reactions, including anaphylaxis, rash, fever, itch, hives, dermatitis, and skin exfoliation, have occurred in patients treated with golodirsen. If these occur during the infusion, notify your healthcare provider immediately. Get emergency medical help if you have signs of an allergic reaction: hives, itching, rash, blistering or peeling, fever, difficult breathing, or swelling of your face, lips, tongue, or throat.
• Kidney damage. golodirsen may damage your kidneys. Your healthcare provider will monitor your kidney function during treatment. Call your doctor at once if you have: pink, brown, or red urine; foamy urine; or swelling in your face, hands, feet, or stomach.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Check serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio before starting golodirsen.

• Usual dosage: Golodirsen 30 mg/kg via IV infusion 1 time a week.
• Infuse over 35 to 60 minutes via an inline 0.2 micron filter. Dilute before administration.

Call your doctor for instructions if you miss an appointment for your golodirsen.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Other drugs may affect golodirsen, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

Golodirsen is only available as the brand Vyondys 53.

Active ingredients: golodirsen 100 mg in 2 mL (50 mg/mL)

Inactive ingredients: Each milliliter contains 0.2 mg potassium chloride, 0.2 mg potassium phosphate monobasic, 8 mg sodium chloride, and 1.14 mg sodium phosphate dibasic, anhydrous, in water for injection. May contain hydrochloric acid or sodium hydroxide to adjust pH.

Formulated as an isotonic phosphate-buffered saline solution with an osmolality of 260 to 320 mOsm and a pH of 7.5.

Available as a 100 mg/2 mL (50 mg/mL) in a single-dose vial for injection. Requires dilution before use.

Golodirsen is manufactured by Sarepta Therapeutics, Inc., under the brand name Vyondys 53. Their headquarters are located in Cambridge, Massachusetts, USA.