General Information

Hemgenix (etranacogene dezaparvovec-drlb) is an adeno-associated virus vector-based gene therapy.

Hemgenix is specifically indicated 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
• Have repeated, serious spontaneous bleeding episodes

Hemgenix is supplied as an injection for single-use intravenous administration. Dosing and Administration is as follows:

• Perform baseline testing to select patients, including testing for Factor IX inhibitor presence and liver health tests.
• The recommended dose of Hemgenix is 2 x 1013 genome copies (gc) per kg of body weight.
• Administer Hemgenix as an intravenous infusion after dilution with 0.9% normal saline at a constant infusion rate of 500 ml/hour (8 mL/min).

Mechanism of Action

Hemgenix (etranacogene dezaparvovec-drlb) is an adeno-associated virus serotype 5 (AAV5) based gene therapy designed to deliver a copy of a gene encoding the Padua variant of human coagulation Factor IX (hFIX-Padua). Single intravenous infusion of Hemgenix results in cell transduction and increase in circulating Factor IX activity in patients with Hemophilia B.

Side Effects

Adverse effects associated with Hemgenix may include, but are not limited to, the following:

• elevated ALT
• headache
• blood creatine kinase elevations
• flu-like symptoms
• infusion-related reactions
• fatigue
• malaise
• elevated AST

Hemgenix carries the potential for hepatocellular carcinogenicity in patients with preexisting risk factors (e.g., cirrhosis, advanced hepatic fibrosis, hepatitis B or C, non-alcoholic fatty liver disease (NAFLD), chronic alcohol consumption, non-alcoholic steatohepatitis (NASH), and advanced age).

Clinical Trial Results

The FDA approval was based on results from the ongoing HOPE-B trial. The open-label, single-arm study enrolled 54 patients. Following a six-month lead-in period, during which patients continued current standard of care therapy to establish a baseline Annual Bleeding Rate (ABR), patients received a single intravenous administration of Hemgenix at the 2x10^13 gc/kg dose.

Results from the study demonstrated that Hemgenix allowed patients to produce mean factor IX activity of 39% at six months and 36.7% at 24 months post infusion. Seven to 18 months post-infusion, the mean adjusted ABR for all bleeds was reduced by 54% compared to the six-

month lead-in period on factor IX prophylactic replacement therapy (4.1 to 1.9). In addition, 94% (51 out of 54) of patients treated with Hemgenix discontinued use of prophylaxis and remained free of previous continuous routine prophylaxis therapy.