Identification
- Generic Name
- Fidanacogene elaparvovec
- DrugBank Accession Number
- DB16783
- Background
Fidanacogene elaparvovec is a liver-specific adeno-associated virus (AAV) vector containing a codon-optimized human coagulation FIX gene that was investigated as a potential treatment for hemophilia B.3 Hemophilia B is a rare X-linked genetic disorder characterized by abnormal coagulation due to dysfunctional coagulation factor IX with a male incidence estimated to be 1 in 30,000 male births worldwide.2 Disease severity is linked to the level of factor IX activity in the blood plasma, ranging from increased bleeding after injuries and surgical operations to spontaneous bleeding, hemorrhages in soft tissues or joints, and severe subcutaneous hematomas. Current available treatments include substitution therapy involving the intravenous administration of standard factor IX once a week for bleeding or as prophylaxis and 2–3 times a week for severe hemophilia, although this carries a significant financial burden to the healthcare system. Other more radical approaches like liver transplants have also been considered.1
On January 3, 2024, fidanacogene elaparvovec was approved by Health Canada under the brand name BEQVEZ for the treatment of adults with moderately severe to severe hemophilia B (congenital Factor IX (FIX) deficiency) who are negative for neutralizing antibodies to variant AAV serotype Rh74.5 This approval was based on positive results demonstrated in the open-label, single-arm Phase 3 BENEGENE-2 study, where the annualized bleeding rate (ABR) was observed to be 1.3 for the 12 months from week 12 to month 15 compared to an ABR of 4.43 for the pre-treatment period.5,3
- Type
- Biotech
- Groups
- Investigational
- Biologic Classification
- Gene Therapies
Other gene therapies - Synonyms
- Fidanacogene elaparvovec
- External IDs
- AAV8 HFIX19
- PF-06838435
- SPARK 101
- SPK-9001
Pharmacology
- Indication
Fidanacogene elaparvovec is an adeno-associated viral (AAV) vector-based gene therapy indicated for the treatment of adults (aged 18 years or older) with moderately severe to severe Hemophilia B (congenital Factor IX deficiency) who are negative for neutralizing antibodies to variant AAV serotype Rh74.4
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Moderately severe hemophilia b •••••••••••• ••••• •••••••• ••• •••••••••••• •••••••••• •• ••••••• ••• •••••••• •••• •••••••••• ••••••••• ••••••••••• Treatment of Severe hemophilia b •••••••••••• ••••• •••••••• ••• •••••••••••• •••••••••• •• ••••••• ••• •••••••• •••• •••••••••• ••••••••• ••••••••••• - Contraindications & Blackbox Warnings
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In the pivotal study C0371002, 45 patients with historical Factor IX activity <2% received fidanacogene elaparvovec. From week 12 to month 15, the levels of Factor IX remained relatively stable. At month 15, 86% patients (30 out of 35) were in or above the mild range (Factor IX activity >5%) based on Factor IX activity measured using the one-stage SynthAsil assay, and 68% and 71% were in or above the mild range based on one-stage Actin-FSL assay and chromogenic assay, respectively.4
In the supportive studies C0371005/1003, Factor IX activity (without imputation) remained stable over time (up to 6 years), with mean Factor IX activity (One-stage Assay with Actin-FSL reagent) at 27.9% at Month 15 (n=9), 24.9% at Month 24 (n=14), 21.5% at Month 48 (Year 4, n=11) and 21.5% at Month 72 (Year 6, n=5). No patient had resumed FIX prophylaxis post-BEQVEZ infusion.4
- Mechanism of action
Fidanacogene elaparvovec is a gene therapy designed to introduce a functional copy of a high activity variant of the Factor IX gene (FIX-R338L) into hepatocytes to address the cause of Hemophilia B.4
Fidanacogene elaparvovec is a non-replicating recombinant AAV vector that utilizes the AAVRh74var capsid to deliver a functional human Factor IX transgene. The AAVRh74var capsid is derived from the Rh74 AAV, which is not known to cause disease in humans. AAVRh74var capsid is able to transduce hepatocytes, the natural site of Factor IX synthesis. The Factor IX gene present in fidanacogene elaparvovec is designed to reside predominately as episomal DNA within transduced cells. Expression of the transgene is driven by a liver-specific promoter, which results in tissue-specific expression. As a result, fidanacogene elaparvovec helps to restore circulating Factor IX procoagulant activity and hemostatic potential in patients with Hemophilia B, which may limit bleeding episodes and the need for exogenous Factor IX treatment.4
- Absorption
In general, peak levels of vector DNA occurred within the first 2 weeks after infusion. Highest peak vector DNA concentrations were found in serum/plasma compared to the other liquid matrices (saliva, urine, semen).4
- Volume of distribution
In a monkey biodistribution study, 22 tissues were collected at 30 and 92 days following treatment. The highest levels of vector DNA were found in the liver with levels approximately 20-fold higher than in the spleen, the organ with the second most abundant levels of genomic DNA. There was very little biodistribution to testes.4
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Vector DNA was shed in peripheral blood mononuclear cells (PBMC), saliva, urine, semen, and serum/plasma.4
- Half-life
Not Available
- Clearance
Clearance of vector DNA was defined as having 3 consecutive results below the limit of quantification (LOQ). Based on this definition, vector DNA was cleared from serum, plasma, saliva, and semen within means of 3, 3, 1.5, and 3 months post-infusion, respectively. Peripheral blood mononuclear cells were the slowest to clear vector DNA with an observed mean of 12 months. In semen, the maximum observed time for vector DNA to clear was 154 days.4
- Adverse Effects
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Avoid excessive or chronic alcohol consumption. Alcohol may reduce drug efficacy and increase the risk of serious hepatic reactions following drug administration.
Products
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Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Beqvez Solution 10000 bvg / mL Intravenous Pfizer Canada Ulc Not applicable Not applicable Canada 
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 413EU9081Y
- CAS number
- 1954659-47-2
References
- General References
- Soroka AB, Feoktistova SG, Mityaeva ON, Volchkov PY: Gene Therapy Approaches for the Treatment of Hemophilia B. Int J Mol Sci. 2023 Jun 28;24(13):10766. doi: 10.3390/ijms241310766. [Article]
- Goodeve AC: Hemophilia B: molecular pathogenesis and mutation analysis. J Thromb Haemost. 2015 Jul;13(7):1184-95. doi: 10.1111/jth.12958. Epub 2015 May 18. [Article]
- Pfizer: Pfizer Announces Positive Top-Line Results from Phase 3 Study of Hemophilia B Gene Therapy Candidate [Link]
- Health Canada Approved Drug Proucts: BEQVEZ (Fidanacogene elaparvovec) Concentrate for solution for intravenous infusion [Link]
- HEALTH CANADA APPROVES PFIZER CANADA'S GENE THERAPY IN HEMOPHILIA B [Link]
- External Links
- Wikipedia
- Spark_Therapeutics
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Hemophilia B 1 2 Active Not Recruiting Treatment Hemophilia B 1 2 Completed Treatment Hemophilia B 1 1 Terminated Treatment Hemophilia B 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution Intravenous 10000 bvg / mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Drug created at May 10, 2022 19:24 / Updated at April 18, 2024 12:56