Etranacogene dezaparvovec-drlb — Drug Monograph

Brand names: Hemgenix

Drug class: Other

Mechanism of Action

Hemgenix is a recombinant AAV5-based gene therapy that delivers a codon-optimized transgene encoding the FIX-Padua variant (R338L gain-of-function) under the control of a liver-specific promoter. The AAV5 capsid efficiently transduces hepatocytes after IV infusion, resulting in episomal vector DNA that drives sustained coagulation factor IX synthesis. FIX-Padua has approximately 8-fold higher specific activity than wild-type FIX, translating to normal or near-normal circulating FIX activity from relatively modest transgene expression. A single infusion results in durable factor IX levels…

FDA Indications

• Moderately severe to severe hemophilia B (congenital factor IX deficiency) — adults with current factor IX prophylaxis, life-threatening hemorrhage, or repeated serious spontaneous bleeding, and without neutralizing antibodies to AAV5 (FDA approved November 22, 2022)

Common Side Effects

• ALT elevation (most common; managed with corticosteroids)
• Infusion-related reactions
• Fatigue
• Headache
• Flu-like symptoms (post-infusion)

Clinical Pearl

Hemgenix was, at launch, the most expensive drug in history ($3.5M per dose for a 70 kg patient) — but demonstrated the model of cost-effectiveness across a lifetime of eliminated prophylaxis costs (~$800K–1M/year for factor IX replacement). In the pivotal HOPE-B trial (n=54), mean annualized bleeding rate decreased 64% and mean factor IX activity reached 41.5 IU/dL at 18 months in 52 of 54 participants. The landmark result: 94% of patients discontinued prophylactic factor IX replacement. At…

Related Therapies & Mechanisms

• Fidanacogene elaparvovec-dzkt (Beqvez) — Other · Hemophilia
• Adagrasib (Krazati) — Other
• Arsenic Trioxide (Trisenox) — Other
• Asparaginase (L-asparaginase, E. coli) (Elspar) — Other