U.S. Food and Drug Administration (FDA)-Approved Indications

Hemgenix is an adeno-associated virus vector-based gene therapy indicated for 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.

Etranacogene dezaparvovec-drlb is available as Hemgenix (CSL Behring LLC) and is an adeno-associated virus serotype 5 (AAV5) based gene therapy developed to carry a copy of a gene encoding the Padua variant of human coagulation Factor IX (hFIX598 Padua). Cell transduction and an increase in circulating Factor IX activity occurs following the single intravenous infusion of Hemgenix (CSL Behring, 2022).

According to the prescribing information, Hemgenix carries the following warnings and precautions:

Per the prescribing information, the most common adverse reactions (incidence ≥5%) were elevated ALT, headache, blood creatine kinase elevations, flu-like symptoms, infusion-related reactions, fatigue, malaise and elevated AST.

Refer to full prescribing information for Hemgenix for use in specific populations.

Hemophilia B is a rare genetic bleeding disorder afflicting individuals who have inadequate levels of factor IX, a blood protein. Factor IX, a clotting factor, is a specialized protein necessary for blood clotting, a process where blood seals a wound to stop bleeding and facilitate healing. Individuals with hemophilia B experience prolonged bleeding in comparison to unaffected individuals. Hemophilia B is caused by mutations in the

(

) gene on the X chromosome, and therefore, is inherited as an X-linked recessive trait. Hemophilia B has an estimated occurrence of 1 in 25,000 male births and is less prevalent than hemophilia A with an estimated occurrence of 1 in 5,000 male births. Typically, female carriers of hemophilia B do not have symptoms, however, approximately 10-25% will develop mild symptoms and may even report moderate and severe symptoms. The disease is classified as mild (e.g., bruising and bleeding after surgery, dental procedures, injury, or trauma), moderate (e.g., occasional episodes of spontaneous bleeding from deep tissues such as joints and muscles), or severe (e.g., frequent, spontaneous bleeding episodes) dependent upon the activity level of factor IX. Individuals with mild hemophilia have factor IX levels between 5 and 40% of normal; moderate hemophilia have factor levels from 1 to 5% of normal; and severe hemophilia have factor levels less than 1% of normal. Diagnosis of hemophilia B is based on the individual's personal history of bleeding, individual's family history of bleeding and inheritance, and laboratory testing. The initial test is the activated partial thromboplastin time (aPTT). Dependent upon aPTT test results, more specific blood testing is performed to determine if the cause of the abnormal aPTT is due to a deficiency of factor IX/hemophilia B, factor VIII/hemophilia A or another clotting factor. Once a diagnosis of hemophilia B is made, then the specific mutation in the

gene responsible for causing hemophilia may be identified. Current treatment options for individuals with hemophilia B include: recombinant factor IX, plasma-derived factor IX concentrates, and fresh frozen plasma (NORD, 2021).

On November 22, 2022, the U.S. Food and Drug Administration (FDA) approved Hemgenix (etranacogene dezaparvovec-drlb), an adeno-associated virus vector-based gene therapy 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. The FDA approval was based on supporting data in two studies evaluating the safety and effectiveness of Hemgenix. These two studies consisted of 57 adult men(18 years to 75 years of age) with severe or moderately severe hemophilia B. In one study, a prospective, open-label, single-dose, single-arm, multi-national study, the individuals (n=54) with severe or moderately severe hemophilia B, received a single intravenous dose of 2 x 10

gc/kg body weight of Hemgenix and entered a follow-up period of 5 years. Effectiveness was determined by decreases in the men's annualized bleeding rate (ABR). Individuals had increases in factor IX activity levels, a decreased need for routine factor IX replacement prophylaxis, and a 54% reduction in ABR compared to baseline (CSL Behring, 2022; FDA, 2022).

: Requires Precertification:

Precertification of etranacogene dezaparvovec-drlb (Hemgenix) is required of all Aetna participating providers and members in applicable plan designs. For precertification of etranacogene dezaparvovec-drlb (Hemgenix),

Prescriber Specialties

This medication must be prescribed by or in consultation with a hematologist.

Criteria for Initial Approval

Hemophilia B

Aetna considers etranacogene dezaparvovec-drlb (Hemgenix) medically necessary for a one dose total for the treatment of hemophilia B when all of the following criteria are met:

Member has severe or moderately severe Factor IX deficiency (less than or equal to 2% of normal circulating Factor IX) and meets

of the following:

Aetna considers all other indications as experimental and investigational.

Continuation of Therapy

See Dosage and Administration information.