The data were evaluated independently from the Prescribing Information and utilized a different methodology for interpreting the data. Therefore, some differences are present between the data from the published clinical trial and the data contained within the Prescribing Information for HEMGENIX.
FIX activity was sustained over 3 years after dosing.2
Click to enlarge
[a] Baseline FIX was imputed based on subject’s historical hemophilia B severity. If the subject had documented severe FIX deficiency (FIX plasma level <1%), their baseline FIX activity level was imputed as 1%. If the subject had documented moderately severe FIX deficiency (FIX plasma level ≥1% and ≤2%), their baseline FIX activity level was imputed as 2%.
Only uncontaminated samples were included in analysis—ie, blood sampling did not occur within 5 half-lives of exogenous FIX use. The lower and upper edges of the box correspond to the interquartile range, the 25th, and the 75th percentile. The line at the middle of the box corresponds to the median. The whiskers (horizontal lines connected to vertical lines) show the lowest and highest observation within 1.5 times the interquartile range of the bottom and top of the box, respectively. The solid circles represent the arithmetic mean. Any points outside of the whiskers are plotted individually.
Abbreviations: aPTT, activated partial thromboplastin time; FIX, factor IX; IQR, interquartile range; Mo, month; Wk, week.
|
Endogenous FIX Activity Levels |
At Year 2 (n=50)3 |
At Year 3 (n=48)1 |
|---|---|---|
| Mean ± SD | 36.7 ± 19.0% | 38.6 ± 17.8% |
| Median | 33.9% | 36.0% |
| IQR | 25.80–45.50%4 | 29.5–48.1% |
| Min - Max | 4.7–99.2% | 4.8–80.3% |
Pharmacodynamic profile was not significantly different in participants with AAV5 NAbs undetected or at a titer ≤1:678.3
Abbreviations: AAV5, adeno-associated virus serotype 5; SD, standard deviation.
Mean annualized bleeding rate (ABR) for all bleeds during months 7–36 post-treatment was significantly reduced, sustaining the same bleed reduction that satisfied the study’s primary endpoint during months 7-18.1
Click to enlarge
*51/54 patients remain free of continuous factor IX prophylaxis. One additional patient required intermittent prophylaxis for approximately 20 weeks during months 7–18.
†P-value is calculated using a paired t-test comparing post-treatment and lead-in periods.
‡One patient died unrelated to treatment at month 15 (prophylaxis-free), and 1 patient who remained on prophylaxis withdrew consent for efficacy assessment.
During the 3 years post-treatment, all participants experienced at least 1 treatment-emergent adverse event (TEAE): 76% were mild, 19% were moderate, and 4% were severe.1
70% (38/54) of participants experienced 96 treatment-related adverse events, of which 95% occurred before 6 months post-treatment.1
The most common adverse event was an increase in alanine transaminase (ALT), for which 9 (16.7%) participants received supportive care with reactive corticosteroids for a mean duration of 81.4 days (SD: 28.6; range: 51–130 days). No late treatment-related ALT elevations or thromboembolic events were reported.1
References: 1. Pipe S, van der Valk P, Verhamme P, et al. Long-term bleeding protection, sustained FIX activity, reduction of FIX consumption and safety of hemophilia B gene therapy: results from the HOPE-B trial 3 years after administration of a single dose of etranacogene dezaparvovec in adult patients with severe or moderately severe hemophilia B. Presented at: ASH Annual Meeting and Exposition; December 11, 2023; San Diego, CA. 2. Data on File. Available from CSL Behring as DOF HGX-005. 3. Pipe SW, van der Valk P, Verhamme P, et al. Long-term bleeding protection, sustained FIX activity, reduction of FIX consumption and safety of hemophilia B gene therapy: results from the HOPE-B trial 3 years after administration of a single dose of etranacogene dezaparvovec in adult patients with severe or moderately severe hemophilia B. Abstract presented at: 65th American Society of Hematology Annual Meeting; December 9-12, 2023; San Diego, CA. Abstract 1055 4. Pipe SW, Castaman G, Miesbach W, et al. Interindividual variability of response to gene therapy in haemophilia B: ranges of factor IX activity levels sustained after 24 months in HOPE-B etranacogene dezaparvovec trial. Abstract presented at: 12th BIC International Conference; September 8-10, 2023; Palermo, Italy.
Warning and Precautions
Infusion Reactions
Infusion reactions, including hypersensitivity reactions and anaphylaxis, may occur. Monitor during administration and for at least 3 hours after end of infusion. If symptoms occur, slow or interrupt administration. Re-start administration at a slower infusion once resolved.
Hepatotoxicity/Hepatocellular Carcinoma
Post-dose, monitor for elevated transaminase levels. Consider corticosteroid treatment should elevations occur. The integration of liver-targeting AAV vector DNA into the genome may carry the theoretical risk of hepatocellular carcinoma development. For patients with preexisting risk factors for hepatocellular carcinogenicity, perform regular (eg, annual) abdominal ultrasound and alpha-fetoprotein testing following administration.
Immune-mediated neutralization of the AAV5 vector capsid
Preexisting neutralizing anti-AAV antibodies may impede transgene expression at desired levels.
Monitoring Laboratory Tests
In addition to monitoring liver function, monitor for Factor IX activity and Factor IX inhibitors after administration.
Adverse Reactions
The most common adverse reactions (incidence ≥5%) were elevated ALT, headache, blood creatine kinase elevations, flu-like symptoms, infusion-related reactions, fatigue, nausea, malaise, and elevated AST.
Indication
HEMGENIX®, etranacogene dezaparvovec-drlb, is an adeno-associated virus vector-based gene therapy indicated for the treatment of adults with Hemophilia B (congenital Factor IX deficiency) who:
HEMGENIX is for single use intravenous infusion only.
Contraindications: None.
Please see full prescribing information for HEMGENIX.
To report SUSPECTED ADVERSE REACTIONS, contact the CSL Behring Pharmacovigilance Department at 1-866-915-6958 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
