Elevidys

/ Roche

For single-dose intravenous infusion only.
The recommended dose is 1.33 × 10¹⁴ vector genomes per kilogram (vg/kg) of body weight (or 10 mL/kg body weight) for patients weighing less than 70 kg or 9.31 × 10¹⁵ vg total fixed dose for patients weighing 70 kg or greater.
Calculate the dose as follows:
Dose (in mL) = patient body weight (rounded to the nearest kilogram) x 10
Number of vials needed = dose (in mL) divided by 10.
Prior to infusion:
* Due to the increased risk of serious systemic immune response, postpone administration in patients with infections until the infection has resolved. Clinical signs or symptoms of infection should not be evident at the time of administration.
* Assess liver function.
* Obtain platelet count and troponin-I levels [see Dosage and Administration.
* Measure baseline anti-AAVrh74 antibody titers using a Total Binding Antibody enzyme-linked immunosorbent assay (ELISA).
* To reduce the risk associated with an immune response, corticosteroids should be administered starting 1 day prior to infusion. Initiate a corticosteroid regimen following the appropriate schedule. This regimen is recommended for a minimum of 60 days after the infusion, unless earlier tapering is clinically indicated.
Administration:
* Do not infuse at a rate of 10 mL/kg/hour or faster
* Consider application of a topical anesthetic to the infusion site prior to administration of IV insertion.
Monitoring Post Administration:
* Assess liver function (clinical exam, GGT, and total bilirubin) weekly for the first 3 months. Continue monitoring if clinically indicated, until results are unremarkable (normal clinical exam, GGT and total bilirubin levels return to near baseline levels).
* Obtain platelet counts weekly for the first two weeks. Continue monitoring if clinically indicated.
* Measure troponin-I weekly for the first month. Continue
monitoring if clinically indicated.
See prescribing information for full details.

Treatment of ambulatory pediatric patients aged 4 to under 8 years with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene.

* 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.
* Hypersensitivity to the active substance or to any of the excipients.

Acute Serious Liver Injury and Acute Liver Failure
Acute serious liver injury marked by elevations of liver enzymes (e.g., GGT, ALT) and total bilirubin and acute liver failure, has occurred with this medical product. Onset of the liver injury typically begins within 8 weeks after administration.
Postpone administration in patients with acute liver disease until resolved or controlled.
Prior to administration, perform liver enzyme test. Monitor liver function (clinical exam, GGT, and total bilirubin) weekly for the first 3 months following infusion. Continue monitoring if clinically indicated, until results are unremarkable.
Serious Infections
Increased susceptibility to serious infections may occur due to concomitant administration of corticosteroid regimen and additional immunosuppressants, and this medical product. Serious respiratory infections, including with fatal outcomes, have occurred in patients taking immunosuppressant corticosteroids required for administration.
Myocarditis
Acute, serious, life-threatening myocarditis and troponin-I elevations have been observed within 24 hours to more than 1 year following treatment.
If a patient experiences myocarditis, those with pre-existing left ventricle ejection fraction (LVEF) impairment may be at higher risk of adverse outcomes. Patients with moderate to severe LVEF impairment have not been studied in clinical trials.
Monitor troponin-I before infusion and weekly for the first month following infusion. Continue monitoring if clinically indicated. More frequent monitoring may be warranted in the presence of cardiac symptoms, such as chest pain or shortness of breath.
Infusion-related Reactions
Infusion-related reactions, including hypersensitivity reactions and anaphylaxis, have occurred during or up to several hours following administration. Closely monitor patients 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.
This medical product should be administered in a setting where treatment for infusion-related reactions is immediately available.
In the event of an infusion-related reaction, administration may be slowed or stopped based on the severity of the patient’s clinical presentation. Administer treatment as needed to manage infusion-related reactions based on the severity of patient’s signs and symptoms. If the infusion was stopped, infusion may be restarted at a lower rate once patient’s symptoms have resolved, at the discretion of the physician. Discontinue infusion for anaphylaxis.
Immune-mediated Myositis
Immune-mediated myositis, including serious and life-threatening events, has occurred approximately 1 month following infusion. Signs and symptoms include severe muscle weakness, including dysphagia, dyspnea, dysphonia, and hypophonia.
These immune reactions may be due to a T-cell based response against specific regions of the microdystrophin transgenic protein. Severe to life-threatening immune-mediated myositis has been reported in patients with deletions including portions of exons 1-17 and/or exons 59-71 of the DMD gene. This medical product 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 due to the increased risk for a severe immune-mediated myositis.
Advise patients to contact a physician immediately if they experience any unexplained increased muscle pain, tenderness, or weakness, including dysphagia, dyspnea or hypophonia as these may be symptoms of myositis. Consider additional immunomodulatory treatment (immunosuppressants [e.g., calcineurin-inhibitor] in
addition to corticosteroids) based on patient’s clinical presentation and medical history if these symptoms occur.
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 medical product all patients developed anti-AAVrh74 antibodies. Perform baseline testing for the presence of anti-AAVrh74 total binding antibodies prior to administration. Administration is not recommended in patients with elevated anti-AAVrh74 total binding antibody titers (≥1:400).
See prescribing information for full details.

The most common adverse reactions (incidence ≥5%) across all studies:
Vomiting, Nausea, Liver injury, Pyrexia, Thrombocytopenia, Troponin-I increased.

Prior to initiating the corticosteroid regimen required before administration this medical product, consider the patient’s vaccination status. Patients should, if possible, be brought up-to-date with all immunizations in agreement with current immunization guidelines. Vaccinations should be completed at least 4 weeks prior to initiation of the corticosteroid regimen.

Pregnancy: This medical product is not intended for use in pregnant women.
Lactation: There is no information available on the presence in human milk, the effects on the breastfed infant, or the effects on milk production.

Storage and Handling
* Shipped and delivered at ≤ −60ºC.
* Refrigerated for up to 14 days when stored at 2°C to 8°C.
* Do not refreeze.
* Do not shake.
* Do not place back in the refrigerator once brought to room temperature.