Hemgenix® (etranacogene dezaparvovec-drlb) is a gene therapy commercialized by CSL Behring that is indicated for the treatment of adult patients with hemophilia B who are undergoing factor IX (FIX) prophylaxis therapy, have a history of life-threatening hemorrhage, or experience repeated, serious, spontaneous bleeding events.1

Hemophilia B is an inherited disease derived from mutations in the gene coding for FIX. FIX is a protein that is mainly produced in the liver and is involved in blood clot formation. Patients with hemophilia B are at risk of experiencing bleeding events, most often into the joints, which can result in degenerative joint disease. Bleeds can also occur in internal organs, which can be painful.2,3 

Hemgenix was approved by the US Food and Drug Administration (FDA) in November 2022, and it is the first gene therapy available for patients with hemophilia B.3

Mechanism of Action and Use of Hemgenix

The standard of care for patients with hemophilia B is life-long prophylactic therapy with FIX.2 These infusions of FIX aim to temporarily replace or supplement low levels of the blood clotting factor. Although this is an effective treatment, it requires lifelong infusion schedules and patients can still suffer from spontaneous bleeding events, joint damage, and pain.3

Hemgenix is an adeno-associated viral (AAV) vector-based gene therapy that is administered in a single dose via an intravenous infusion. This drug is a nonreplicating recombinant AAV serotype 5 (AAV5) that, once administered, targets liver cells to deliver a copy of the gene that encodes the Padua variant of the human coagulation FIX.1 A single administration of Hemgenix, with the delivery of genetic instructions to the cells, enables patients to keep producing stable levels of FIX proteins that are 5 to 8 times more active. By this mechanism, Hemgenix can help decrease the risk of bleeding events.3

Eligibility to receive Hemgenix is determined by testing the presence of FIX inhibitors in the blood. The recommended dose of Hemgenix is 2×1013 genome copies/kg (or 2 mL/kg). The administration of this medication should occur after dilution with 0.9% sodium chloride, and patients should be monitored for infusion reactions during administration and for at least 3 hours after.1 

Liver enzyme levels in the blood may elevate with Hemgenix administration and therefore require close monitoring to avoid hepatotoxicity. Patients carrying pre-existing risk factors for hepatocellular carcinoma also require monitoring via abdominal ultrasound screening and alpha-fetoprotein (AFP) levels.1

In addition to infusion-related reactions, common adverse reactions following Hemgenix administration include elevated liver enzymes, headache, flu-like symptoms, fatigue, and malaise.1

Hemgenix in Clinical Trials

A phase 2b clinical trial was conducted to confirm FIX activity deriving from Hemgenix (NCT03489291).4 This study showed that Hemgenix was well tolerated, leading to an increase in FIX activity (>40% after 26 weeks), cessation of bleeds, and no need for FIX replacement despite the presence of pre-existing anti-AAV5 neutralizing antibodies.5 

A planned interim analysis following the phase 2b study has been recently reported, supporting the stable and durable expression of endogenous FIX within a normal range and over a 3-year period in these patients.2

The approval of Hemgenix followed the results of the phase 3 clinical trial HOPE-B (NCT03569891).6 This is an ongoing, multinational, open-label, single-arm trial designed to study both the safety and efficacy of Hemgenix. HOPE-B enrolled adult patients with hemophilia B who required prophylactic treatment with FIX. Patients were initially included in a prospective observational study for at least 6 months. During this period, 54 patients continued with their standard of care, which allowed investigators to determine the baseline annualized bleeding rate (ABR). Following the observational period, patients received a single dose of Hemgenix at the recommended dose and were scheduled for follow-ups for up to 5 years. Efficacy evaluation was based on data reported up to 18 months after treatment in 53 patients.1

Results from the phase 3 trial reported an estimated mean ABR between months 7 and 18 of 1.9 bleeds/year following Hemgenix treatment compared to 4.1 bleeds/year reported in the observational period.1 There were no reports of serious adverse reactions or any observed development of inhibitors to FIX.3


1. Hemgenix. Prescribing information. CSL Behring LLC; 2022. Accessed December 19, 2022.

2. von Drygalski A, Gomez E, Giermasz A, et al. Stable and durable factor IX levels in hemophilia B patients over 3 years post etranacogene dezaparvovec gene therapy. Blood Adv. Published online December 9, 2022. doi:10.1182/bloodadvances.2022008886

3. uniQure announces FDA approval of first gene therapy for adults with hemophilia B. News release. uniQure; November 22, 2022.

4. Dose confirmation trial of AAV5-hFIXco-Padua. ClinicalTrials.gov. April 5, 2018. Updated June 16, 2022. Accessed December 19, 2022.

5. Von Drygalski A, Giermasz A, Castaman G, et al. Etranacogene dezaparvovec (AMT-061 phase 2b): normal/near normal FIX activity and bleed cessation in hemophilia B. Blood Adv. 2019;3(21):3241-3247. doi:10.1182/bloodadvances.2019000811

6. HOPE-B: trial of AMT-061 in severe or moderately severe hemophilia B patients. ClinicalTrials.gov. June 26, 2018. Updated October 10, 2022. Accessed December 19, 2022.

Reviewed by Harshi Dhingra, MD