Etranacogene Dezaparvovec

Etranacogene Dezaparvovec is a prescription medication used for the treatment of adults with hemophilia B (congenital Factor IX deficiency) who currently use Factor IX prophylaxis therapy, or have current or historical life-threatening hemorrhage or repeated serious spontaneous bleeding episodes.

• Etranacogene Dezaparvovec is available under the following different brand names: Hemgenix, etranacogene Dezaparvovec-drlb

Common side effects of Etranacogene Dezaparvovec include:

• headache
• flu-like symptoms
• infusion-related reactions (chest tightness, abdominal pain, light-headedness, shivering, flushing, rash, and high blood pressure)
• fatigue
• feeling unwell (malaise)
• elevated alanine transaminase
• blood creatine kinase elevations
• elevated aspartate aminotransferase

Serious side effects of Etranacogene Dezaparvovec include:

• hives
• difficulty breathing
• swelling of the face, lips, tongue, or throat
• chest pain or pressure
• headache
• abdominal pain
• lightheadedness
• shivering
• flushing
• rash
• high blood pressure

Rare side effects of Etranacogene Dezaparvovec include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, light-headedness, or passing out

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Injection, suspension

• 1 × 1013 genome copies (gc)/mL; each vial contains an extractable volume of at least 10 mL
• Provided as a kit containing 10-48 vials; each kit constitutes a dosage unit based on the patient’s body weight
• Clear, colorless suspension for IV infusion

Hemophilia B

Adult dosage

• 2 × 1013 gc/kg IV (2 mL/kg) as a single one-time dose
• Number of vials needed = dose (in mL) divided by 10 (round up to next whole number of vials)
• Division factor 10 represents the extractable volume from each vial (ie, 10 mL)
• Example for a 72 kg patient
  • 2 gc (mL)/kg × 72 kg = 144 mL
  • 144 mL rounded up to 150 mL (ie, 15 vials [10 mL/vial])

Dosage Considerations – Should be Given as Follows:

• See "Dosages"

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Etranacogene Dezaparvovec has no noted severe interactions with any other drugs.
• Etranacogene Dezaparvovec has no noted serious interactions with any other drugs.
• Etranacogene Dezaparvovec has no noted moderate interactions with any other drugs.
• Etranacogene Dezaparvovec has no noted minor interactions with any other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Etranacogene Dezaparvovec?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Etranacogene Dezaparvovec?”

Cautions

• Infusion reactions
  • Infusion reactions, including hypersensitivity reactions and anaphylaxis, may occur
  • Symptoms may include chest tightness, headaches, abdominal pain, light-headedness, flu-like symptoms, shivering, flushing, rash, and hypertension
  • Closely monitor for signs or symptoms throughout the infusion period and for at least 3 h after the end of the infusion
  • Do not exceed the infusion rate of 500 mL/h
  • If an infusion reaction occurs, slow rate or stop and restart at a slower rate once the reaction resolves
  • Consider treatment with a corticosteroid or an antihistamine for the management of an infusion reaction
• Hepatotoxicity
  • IV administration of a liver-directed adeno-associated virus (AAV) vector may lead to liver transaminase elevations (transaminitis)
  • Transaminitis, particularly in the first 3 mo after administration, is presumed to occur owing to immune-mediated injury of transduced hepatocytes and may reduce the therapeutic efficacy of the gene therapy
  • Closely monitor transaminase levels weekly for 3 mo after administration to mitigate the risk for hepatotoxicity
  • Continue to monitor transaminases in all patients who developed liver enzyme elevations until enzymes return to baseline
  • In case of increased alanine transaminase levels more than the ULN or double baseline levels, consider implementing a course of corticosteroid, along with human Factor IX (FIX) activity monitoring
• Immune-mediated neutralization of the AAV5 vector capsid
  • In AAV-vector-based gene therapies, preexisting neutralizing anti-AAV antibodies may impede transgene expression at desired therapeutic levels
  • Following treatment, all subjects developed neutralizing anti-AAV antibodies
  • Currently, there is no validated neutralizing anti-AAV5 antibody assay
  • Anti-AAV5 antibody study
  • Encourage patients who intend to receive treatment to enroll in a study to measure preexisting anti-AAV5 neutralizing antibodies by calling CSL Behring at 1-800-504-5434
  • Study evaluates the effect of preexisting anti-AAV5 neutralizing antibodies on bleeding risk
• Hepatocellular carcinogenicity
  • Integration of liver-targeting AAV vector DNA into the genome may carry a theoretical risk for hepatocellular carcinoma development
  • Etranacogene Dezaparvovec is composed of a nonreplicating AAV5 vector whose DNA persists largely in episomal form
  • Random integration of the vector DNA to the human DNA at low frequency is possible
  • No etranacogene Dezaparvovec–associated clonal expansion or carcinogenicity was observed in clinical studies
  • One subject with preexisting risk factors for developing hepatic cancer developed a hepatocellular carcinoma, which was assessed as not likely related to treatment based on vector integration site analyses and whole genome sequencing
  • Perform abdominal ultrasound screenings in patients with preexisting risk factors for hepatocellular carcinoma (eg, patients with cirrhosis, advanced hepatic fibrosis, hepatitis C or B, nonalcoholic fatty liver disease, chronic alcohol consumption, nonalcoholic steatohepatitis, advanced age)
  • Monitor regularly (eg, annually) for alpha-fetoprotein elevations for 5 y after administration
• Monitoring laboratory tests
  • After administration, regularly monitor FIX activity levels (eg, weekly × 3 mo)
  • When using an in vitro activated partial thromboplastin time (aPTT)–based one-stage clotting assay (OSA) for determining FIX activity, plasma FIX activity results can be affected by both the type of aPTT reagent and the reference standard used in the assay
  • This is important to consider, particularly when changing laboratory and/or reagents used in the assay
  • Therefore, the same assay and reagents are recommended to be used to monitor FIX activity over time
  • Results of FIX activity tests are lower if measured with chromogenic substrate assay (CSA) than those measured with OSA
  • In the clinical efficacy study, post-dose FIX activity measured with CSA returned lower values, with the mean CSA-to-OSA FIX activity ratio ranging from 0.41-0.55
  • Monitor through appropriate clinical observations and laboratory tests for the development of inhibitors to FIX after administration
  • Perform an assay that detects FIX inhibitors if bleeding is not controlled or plasma FIX activity levels decrease

Pregnancy and Lactation

• Not intended for administration in women
• FIX deficiency is an X-linked inherited bleeding disorder, usually manifested in men and transmitted by women who carry the causative mutation on the X chromosome
• Lactation
  • Not intended for administration in women