Elevidys

Elevidys is a gene therapy designed to treat Duchenne muscular dystrophy (DMD). Elevidys works by helping the body produce a protein called micro-dystrophin, which may strengthen muscles and improve motor function.

Elevidys is given as a one-time intravenous (IV) infusion, meaning patients receive a single dose through a vein.

Elevidys is FDA-approved to treat Duchenne muscular dystrophy (DMD) in patients 4 years and older who are ambulatory (can walk) and have a confirmed mutation in the DMD gene. FDA approval was first granted to Sarepta Therapeutics on June 22, 2023.

This medicine should not be used if you have elevated levels of antibodies to the Elevidys vector (AAVrh74) or if you have any deletion in exon 8 and/or exon 9 in the DMD gene.

Elevidys helps the body make a protein (micro-dystrophin) that prevents muscle cells from degenerating, which may help strengthen muscles and improve motor function.

In Duchenne muscular dystrophy, the defective gene means the dystrophin protein does not function properly. Elevidys is a gene therapy that introduces the code or instructions on how to make the most important sections of the dystrophin protein. It does not make the whole protein, as the code is too large. The introduced code makes microdystrophin, which contains selected sections of dystrophin protein present in normal muscle cells, and is hoped to improve motor function. A clinical benefit of this medicine has not been established, as it is still being studied whether it will improve physical function and mobility.

Elevidys' mechanism of action is as an adeno-associated virus vector-based gene therapy

Duchenne muscular dystrophy is a serious but rare genetic condition that becomes worse over time, leading to weakness and wasting away of the body’s muscles. The cause of Duchenne muscular dystrophy is a defective gene that codes for the dystrophin protein, an important component of muscle cells.

The lack of dystrophin causes symptoms such as trouble walking and running, falling frequently, fatigue, learning disabilities/difficulties, heart issues due to the impact on the heart muscle, and breathing problems due to weakness of respiratory muscles involved in breathing.

Symptoms typically begin in childhood, often between 3 to 6 years old, and as the disease progresses, life-threatening heart and respiratory problems can occur. Disease severity and life expectancy do vary, but patients often succumb to the disease in their 20s or 30s because of heart and/or respiratory failure.

• Elevidys is a single-dose (one-time treatment) given as an intravenous infusion.
• Before the infusion of this medicine, you will have your liver function assessed and other blood tests.
• You should not have an infusion while you have an infection.
• To reduce the risk associated with an immune response, you may be prescribed corticosteroids starting one day before the infusion.

Patients’ immunizations should be up-to-date with current immunization guidelines before starting the corticosteroid regimen required for Elevidys infusion. Vaccinations should be completed at least 4 weeks prior to initiation of the corticosteroid regimen.

ACUTE SERIOUS LIVER INJURY AND ACUTE LIVER FAILURE: Elevidys can cause acute serious liver injury, including life-threatening and fatal acute liver failure. Patients with preexisting liver impairment are at higher risk.

Critical safety measures:

Before your infusion: Your healthcare provider will assess your liver function through clinical examination and laboratory testing. You will receive systemic corticosteroids before and after your Elevidys infusion to help protect your liver.

After the infusion: Your doctor will monitor your liver function weekly for the first 3 months following infusion and will continue monitoring until your results return to normal.

• You must stay near an appropriate healthcare facility (as determined by your healthcare provider) for at least 2 months after receiving Elevidys.
• If your doctor suspects you have an acute, serious liver injury, they will promptly consult with a liver specialist (gastroenterologist or hepatologist).

Warning signs of liver injury:

Contact your doctor immediately if you experience:

• Yellowing of skin or eyes (jaundice)
• Dark urine
• Nausea or vomiting
• Loss of appetite
• Pain in the upper right abdomen
• Unusual tiredness or weakness
• Easy bruising or bleeding.

Infusion-related reactions, including hypersensitivity reactions and anaphylaxis, have occurred during or up to several hours following infusion. Patients are closely monitored during and for at least 3 hours after the end of infusion for signs and symptoms of infusion-related reactions, including tachycardia, tachypnea, lip swelling, difficulty breathing, nasal flaring, urticaria, flushing, lip pruritus, rash, cheilitis, vomiting, nausea, rigors, and pyrexia.

Immune-mediated myositis (an immune response affecting muscles). Patients should contact their healthcare provider immediately if they experience any unexplained increased muscle pain, tenderness, or weakness, including difficulty swallowing, difficulty breathing, or a weak voice, as these may be myositis symptoms.

Acute serious myocarditis (inflammation of the heart) and troponin-I elevations have been observed following Elevidys infusion in clinical trials. Patients should contact their healthcare provider immediately if they experience chest pain and/or shortness of breath.

Pre-existing Immunity against AAVrh74 in AAV-vector-based gene therapies. Preexisting anti-AAV antibodies may impede transgene expression at desired therapeutic levels. Following treatment with this infusion, all patients developed anti-AAVrh74 antibodies. Perform baseline testing for the presence of anti-AAVrh74 total binding antibodies before infusion. This infusion should not be administered in patients with elevated anti-AAVrh74 total binding antibody titers (≥1:400)

Serious Infections. Serious infections with fatal outcomes may occur due to concomitant administration of corticosteroids, additional immunosuppressants, and Elevidys. Contact a healthcare provider immediately if symptoms suggestive of infection are observed (e.g., coughing, wheezing, sneezing, runny nose, sore throat, or fever).

Absolute Contraindications

Elevidys is contraindicated in patients with any deletion in exon 8 and/or exon 9, including a deletion of any portion or the entirety of these exons, in the DMD gene.

Elevidys is not recommended if you have:

• Liver problems: Do not receive Elevidys if you have existing liver impairment or active hepatitis (liver viral infection). This includes having elevated liver enzymes (GGT more than 2 times the normal upper limit) or high bilirubin levels (above normal range, unless you have Gilbert's syndrome). Patients with liver problems face a significantly higher risk of serious liver injury and liver failure.
• Recent vaccinations: Wait at least 4 weeks after receiving any vaccination before getting Elevidys. Similarly, avoid getting vaccinated within 4 weeks before your infusion. This timing helps reduce immune system complications and safety concerns.
• Active or recent infections: Do not receive Elevidys if you currently have an infection or have had an infection within the past 4 weeks. Your body needs to be infection-free to safely receive this treatment.

Talk to your healthcare provider about your complete medical history, including any liver conditions, recent vaccinations, or infections, to determine if Elevidys is appropriate for you.

Common Elevidys side effects were vomiting (65%), nausea (43%), liver injury (40%), fever (28%), and low blood platelet levels (8%). These were the side effects that affected 5% or more patients in clinical studies.

The following are clinically significant Elevidys side effects:

• acute serious liver injury, liver failure, and death
• immune-mediated inflammation of muscles (myositis)
• inflammation of the heart (myocarditis)
• hypersensitivity reactions and anaphylaxis
• infections.

The dose of Elevidys is based on body weight.

Patients weighing 10 to 70 kg: The recommended dose is 1.33 × 1014 vector genomes per kilogram (vg/kg) of body weight (or 10 mL/kg body weight).

Patients 70 kg or greater: Maximum dose of 9.31 × 1015 vg total fixed dose.

Note: One day before the infusion, your healthcare provider will start corticosteroids, which you will continue with for a minimum of 60 days.

• Your healthcare provider may modify your corticosteroid dose if you have liver function abnormalities.

Before starting the corticosteroid regimen required before Elevidys infusion, consider the patient’s vaccination status. Patients should, if possible, be brought up-to-date with all immunizations in current immunization guidelines. Vaccinations should be completed at least 4 weeks before starting the corticosteroid regimen.

HCPs and patients often use the Elevidys Package Insert (PI) for more detailed information about this medicine. The Elevidys Package Insert (prescribing information) contains more comprehensive information on Indications and Usage, Dosage and Administration, Clinical Pharmacology, Clinical Studies, Drug Interaction, and more. Discuss any medical questions you have with your HCP (health care professional). This is not all the information you need to know about this medicine for safe and effective use, and it does not take the place of talking to your doctor about your treatment.

The Package Insert is sometimes called Elevidys Prescribing Information (PI) or FDA label.

Elevidys J code is J1413.J codes are used for medicines that are not taken orally and include injections, inhalations, and chemotherapies. J codes are important for accurate and consistent coding for billing and reimbursement purposes.

Your physician will need the Elevidys J code when filling out forms for your treatment.

• Infusion is shipped and delivered at ≤ −60ºC [−76ºF].
• Infusion can be refrigerated for up to 14 days when stored at 2°C to 8°C (36º F to 46º F) in the upright position.
• Do not refreeze.
• Do not shake.
• Do not place back in the refrigerator once brought to room temperature.
• Follow local guidelines on handling biological waste.

Manufactured for: Sarepta Therapeutics, Inc., Cambridge, MA 02142 USA