Last update 21 Nov 2024

Fidanacogene elaparvovec

Last update 21 Nov 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

AAV based gene therapy

Synonyms

AAV8 factor IX gene therapy, Durveqtix, Fidanacogene Elaparvovec-dzkt

+ [8]

Target

factor IX

Mechanism

Factor IX gene transference

Therapeutic Areas

Congenital DisordersHemic and Lymphatic DiseasesOther Diseases

Active Indication

Hemophilia B

Inactive Indication-

Originator Organization

The Children's Hospital of Philadelphia

Active Organization

Pfizer Inc.Pfizer Europe MA EEIGPfizer Canada ULC

Inactive Organization

Spark Therapeutics, Inc.

Genzyme Corp.

Avigen, Inc.

+ [1]

Drug Highest PhaseApproved

First Approval Date

CA (27 Dec 2023),

Hemophilia B

RegulationPRIME (EU), Conditional marketing approval (EU), Orphan Drug (EU), Breakthrough Therapy (US)

Clinical Trials associated with Fidanacogene elaparvovec

NCT03861273 / Active, not recruitingPhase 3

Phase 3, Open-label, Single-arm Study to Evaluate Efficacy and Safety of FIX Gene Transfer With PF-06838435 (rAAV-Spark100-hFIX-R338L) in Adult Male Participants With Moderately Severe to Severe Hemophilia B (FIX:C =2%) (BeneGene-2)

This study will evaluate the efficacy and safety of PF-06838435 (a gene therapy drug) in adult male participants with moderately severe to severe hemophilia B (participants that have a Factor IX circulating activity of 2% or less). The gene therapy is designed to introduce genetic material into cells to compensate for missing or non-functioning Factor IX. Eligible study participants will have completed a minimum 6 months of routine Factor IX prophylaxis therapy during the lead in study (C0371004). Participants will be dosed once (intravenously) and will be evaluated over the course of 6 years. The main objective of the study will evaluate the annualized bleeding rate [ABR] for participants treated with gene therapy versus standard of care (SOC) therapy (FIX prophylaxis replacement regimen).

Start Date29 Jul 2019

Sponsor / Collaborator

Pfizer Inc.

NCT03307980 / Active, not recruitingPhase 2

A FACTOR IX (FIX) GENE TRANSFER, MULTI CENTER EVALUATION OF THE LONG TERM SAFETY AND EFFICACY STUDY OF PF 06838435 AND A DOSE ESCALATION SUBSTUDY IN INDIVIDUALS WITH HEMOPHILIA B

Long-term safety and efficacy follow-up for participants with Hemophilia B who were previously treated in the C0371005 (formerly SPK-9001-101) study, and a dose-escalation sub-study evaluating safety, tolerability, and kinetics of a higher dose with long-term safety and efficacy follow-up. Participants in the substudy do not need to have participated in C0371005.

Start Date22 Jun 2017

Sponsor / Collaborator

Pfizer Inc.

NCT02484092 / CompletedPhase 2

Gene Therapy, Open-label, Dose-escalation Study of PF-06838435 (SPK-9001) [Adeno-associated Viral Vector With Human Factor IX Gene] in Subjects With Hemophilia B

A Phase 1/2, Open-Label, Non-Randomized, Dose-Escalation Study of SPK-9001 in Subjects with Hemophilia B.

Start Date18 Nov 2015

Sponsor / Collaborator

Pfizer Inc.

100 Clinical Results associated with Fidanacogene elaparvovec

100 Translational Medicine associated with Fidanacogene elaparvovec

100 Patents (Medical) associated with Fidanacogene elaparvovec

Literatures (Medical) associated with Fidanacogene elaparvovec

01 Oct 2024·Thrombosis and Haemostasis

Field Study and Correlative Studies of Factor IX Variant FIX-R338L in Participants Treated with Fidanacogene Elaparvovec

Article

Author: Murphy, John E. ; Rupon, Jeremy ; Marshall, Jean-Claude ; Pittman, Debra D. ; Rakhe, Swapnil ; Carrieri, Charles ; Tan, Charles Y. ; Soares, Holly ; Liang, John Z. ; Gaitonde, Puneet ; McKay, John

Background Fidanacogene elaparvovec, an adeno-associated virus-based gene therapy vector expressing the high-activity factor IX (FIX) variant FIX-R338L, is in development for hemophilia B. One-stage clotting (OS) assays and chromogenic substrate (CS) assays are commonly used to measure FIX-R338L variant activity. Data from ongoing trials suggest FIX activity varies between different OS and CS assays. Material and Methods To better understand FIX-R338L activity in clinical samples, an international multisite field study was conducted across a central laboratory and 18 local laboratories, using standard protocols, reagents, and instrumentation, with individual participant samples from a phase 1/2a study of fidanacogene elaparvovec. Results Unlike the wild-type FIX control, FIX-R338L activity was higher with the OS silica-based assay versus OS ellagic acid–based and CS assays. Variation in FIX activity was greater at the lowest activity levels. Activated FIX (FIXa) in plasma could result in higher OS assay activity or increased thrombin generation, which could overestimate FIX activity. However, FIXa was not detected in the participant samples, indicating that it was not contributing to the OS assay differences. Since individuals on gene therapy may receive exogenous replacement FIX products, replacement products were spiked into patient plasma samples to target a therapeutic concentration. Exogenous FIX was additive to endogenous FIX-R338L, with no interference from FIX-R338L. Conclusion These results demonstrate FIX-R338L activity can be measured with OS and CS assays in clinical laboratories and provide insight into assay variability when measuring FIX with endogenously produced FIX-R338L. The findings may help establish best practices for measuring FIX-R338L activity (Clinicaltrials.gov identifier: NCT02484092).

26 Sep 2024·New England Journal of Medicine

Gene Therapy with Fidanacogene Elaparvovec in Adults with Hemophilia B

Article

Author: Biondo, Francesca ; Klamroth, Robert ; Astermark, Jan ; Wang, Jiaan-Der ; Ishiguro, Akira ; Shapiro, Amy D ; Teitel, Jerome ; Sun, Pengling ; Leavitt, Andrew D ; Fang, Annie ; McKay, John ; Rasko, John E J ; Cuker, Adam ; Katsarou-Fasouli, Olga ; Oldenburg, Johannes B ; Iorio, Alfonso ; Hermans, Cédric ; Ozelo, Margareth C ; Rupon, Jeremy ; Cerqueira, Monica H ; Fuiman, Joanne ; Kavakli, Kaan ; Frenzel, Laurent

BACKGROUNDFidanacogene elaparvovec, an adeno-associated virus (AAV) gene-therapy vector for hemophilia B containing a high-activity human factor IX variant (FIX-R338L/FIX-Padua), was associated with sustained factor IX activity in a phase 1-2a study.METHODSWe conducted a phase 3 open-label study of fidanacogene elaparvovec at a dose of 5×10¹¹ vector genome copies per kilogram of body weight. Men 18 to 65 years of age with hemophilia B and a factor IX level of 2% or less were eligible for screening if they had received at least 6 months of therapy with prophylactic factor IX concentrate. The primary end point, tested for noninferiority, was the annualized bleeding rate (treated and untreated bleeding episodes) from week 12 to month 15 after treatment with fidanacogene elaparvovec as compared with the prophylaxis lead-in period. Superiority, additional efficacy end points, and safety were also assessed.RESULTSOf 316 men who underwent screening for the lead-in study, 204 (64.6%) were not eligible; 188 (59.5%) of those were ineligible owing to the presence of anti-AAV neutralizing antibodies. Of the 45 participants who received fidanacogene elaparvovec, 44 completed at least 15 months of follow-up. The annualized rate of bleeding for all bleeding episodes decreased by 71%, from 4.42 (95% confidence interval [CI], 1.80 to 7.05) at baseline to 1.28 (95% CI, 0.57 to 1.98) after gene therapy, a treatment difference of -3.15 episodes (95% CI, -5.46 to -0.83; P = 0.008). This result shows the noninferiority and superiority of fidanacogene elaparvovec to prophylaxis. At 15 months, the mean factor IX activity was 26.9% (median, 22.9%; range, 1.9 to 119.0) by one-stage SynthASil assay. A total of 28 participants (62%) received glucocorticoids for increased aminotransferase levels or decreased factor IX levels (or both) starting between 11 and 123 days. No infusion-related serious adverse events, thrombotic events, development of factor IX inhibitors, or malignant conditions were observed.CONCLUSIONSFidanacogene elaparvovec was superior to prophylaxis for the treatment of participants with hemophilia B, leading to reduced bleeding and stable factor IX expression. (Funded by Pfizer; BENEGENE-2 ClinicalTrials.gov number, NCT03861273.).

01 Apr 2024·Drugs

Fidanacogene Elaparvovec: First Approval

Review

Author: Dhillon, Sohita

Fidanacogene elaparvovec (^PrBEQVEZ™) is an adeno-associated viral (AAV) vector-based gene therapy developed by Spark Therapeutics (a subsidiary of Roche) and Pfizer (under a license from Spark Therapeutics) for the treatment of haemophilia B. In December 2023, fidanacogene elaparvovec received its first approval for the treatment of adults (aged ≥ 18 years) with moderately severe to severe haemophilia B (congenital factor IX deficiency) who are negative for neutralizing antibodies to variant AAV serotype Rh74 (AAVRh74var). Fidanacogene elaparvovec is under regulatory review in the USA and the European Union and clinical studies are ongoing in multiple countries. This article summarizes the milestones in the development of fidanacogene elaparvovec leading to this first approval for moderately severe to severe (factor IX activity ≤ 2%) haemophilia B who are negative for neutralizing antibodies to AAVRh74var.

News (Medical) associated with Fidanacogene elaparvovec

24 Oct 2024

·www.pharmaceutical-technology.com

Be Bio raises $82m to advance haemophilia B gene therapy to Phase I/II trial

Be Bio’s BE-101 works by inserting the human Factor IX (FIX) gene into primary human B cells. Image credit: Shutterstock/ ardhikauw. Be Biopharma has raised $82m in financing to advance a gene therapy targeting hemophilia B to a Phase I/II trial, whilst also adding an ex-Roche exec who was involved with the launch of a haemophilia A treatment to its roster. The financing had big pharma involvement in the form of Bristol Myers Squibb and Takeda Ventures, with venture capital firms ARCH Venture Partners, Atlas Venture, and RA Capital Management participating. Be Bio said the funds, which were also from Alta Partners and the Longwood Fund, will be allocated to the hemophilia B candidate BE-101 and a newly unveiled programme for hypophosphatasia called BE-102. Alongside the funds, the US biopharma added Suha Patel and Dr. Kiran Patki to its ranks, who will serve as senior vice president of commercial & franchise strategy and senior vice president of clinical development, respectively. Patel was involved in launching the haemophilia A treatment Hemlibra (emicizumab-kxwh) at Roche’s Genentech, whilst Patki previously worked at rare disease biotech Rally Bio. Be Bio’s CEO Dr. Joanne Smith-Farrell said that “some valued colleagues will be moving on” as the company shifts resources toward product development. Be Bio’s BE-101 is a genetically engineered B cell therapeutic that works by inserting the human Factor IX (FIX) gene into primary human B cells, which allows for continuous expression of active FIX levels with a single infusion. Haemophilia B, which affects around 40,000 globally, is an X-linked recessive bleeding disorder caused by a deficiency in clotting factor IX and has traditionally been treated with regular infusions of the protein. The advancement of gene therapies is changing the treatment paradigm for this disorder, with single infusions reducing the burden on patients taking repeated treatments. There are currently two US Food and Drug Administration (FDA)-approved gene therapies for haemophilia B – CSL Behring’s Hemgenix (etranacogene dezaparvovec) and Pfizer’s Beqvez (fidanacogene elaparvovec ). Be Bio’s candidate has an FDA orphan drug designation and fast track status, which confers benefits such as the possibility of seven years of market exclusivity. See Also: TreeFrog and University of Pittsburgh probe TLS role in immuno-oncology Lilly’s Kisunla does not demonstrate “good value” for UK’s NHS The FDA approved an investigational new drug application (IND) in March this year, greenlighting the company to initiate a trial evaluating the gene therapy. The multi-centre, first-in-human dose escalation study (NCT06611436), called BeCoMe-9, will evaluate the safety and preliminary efficacy of intravenously administered BE-101 in adults with moderately severe to severe haemophilia B. The trial is estimated to enrol 24 patients and has a primary endpoint of adverse events and serious adverse events one year post dose. Smith-Farrell said: “We are eager to clinically demonstrate BE-101’s potential to provide a highly durable FIX replacement therapy for Hemophilia B patients. Additionally, we are excited to advance BE-102 to address the needs of a large patient population with few to no therapeutic options.” Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Cell and gene therapies: Pipe dream to pipeline The cell and gene industry is gaining momentum, with a new wave of therapies promising to transform the way doctors treat, and even cure, disease. In this report, Cytiva and GlobalData have collaborated to explore the rise of the cell and gene therapy industries, the current state of the market, present and future opportunities for advancement, and the challenges that lie ahead. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. By Cytiva Thematic By downloading this Whitepaper, you acknowledge that GlobalData may share your information with Cytiva Thematic and that your personal data will be used as described in their Privacy Policy

Orphan DrugGene TherapyFast TrackClinical Study

16 Oct 2024

·pmlive.com

Pfizer’s Hympavzi granted FDA approval to treat haemophilia in adult and paediatric patients

Pfizer’s anti-tissue factor pathway inhibitor Hympavzi (marstacimab-hncq) has been approved by the US Food and Drug Administration (FDA) to treat haemophilia A or B in adult and paediatric patients aged 12 years and older. Hympavzi, which is now the first in its drug class to be approved in the US for haemophilia A or B, has been specifically authorised for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with haemophilia A without factor VIII inhibitors or haemophilia B without factor IX inhibitors. More than 800,000 people globally are affected by haemophilia, a family of rare genetic blood disorders caused by a clotting factor deficiency. Despite recent progress in haemophilia treatment, many patients continue to experience repeated bleeding episodes and manage their condition with frequent intravenous infusions that may need to be given multiple times a week. Administered as a once-weekly subcutaneous injection, Hympavzi works by reducing the amount of the naturally occurring anticoagulation protein, tissue factor pathway inhibitor. This increases the amount of thrombin, an enzyme critical in blood clotting, that is generated. The FDA’s decision was supported by positive results from the late-stage BASIS trial, in which Hympavzi reduced the annualised bleeding rate for treated bleeds by 35% and 92% after a 12-month active treatment period compared to routine prophylaxis and on-demand treatment, respectively, in patients with haemophilia A or B without inhibitors. Ann Farrell, director of the division of non-malignant haematology in the FDA’s Center for Drug Evaluation and Research, said the approval “provides patients with haemophilia a new treatment option that is the first of its kind to work by targeting a protein in the blood clotting process”. The authorisation comes less than six months after the FDA approved Pfizer’s one-time haemophilia B gene therapy Beqvez (fidanacogene elaparvovec-dzkt) for use in certain adults with moderate-to-severe cases of the disorder. The company also has a range of recombinant factor treatments. Aamir Malik, Pfizer’s chief US commercial officer and executive vice president, said: “We look forward to launching this latest medical breakthrough and to now offer three distinct classes of haemophilia medicines… that can meet the unique treatment needs of a wide range of patients.”

Drug ApprovalGene TherapyClinical Result

14 Oct 2024

·www.echemi.com

Pfizer's Drug Hympavzi Approved: The Shocking Price of $795,600 Shakes the Hemophilia Treatment Market

Six months after successfully winning U.S. Food and Drug Administration (FDA) approval for Beqvez, a gene therapy to treat hemophilia B, Pfizer is once again on the cusp of another important product indication approval. On Friday, the FDA officially approved Hympavzi (marstacimab-hncq), A novel anti-tissue factor pathway inhibitor specifically designed to treat patients 12 years of age and older with hemophilia A or B, particularly those who have not developed antibodies to prior inhibitor therapy. Hympavzi is an innovative once-a-week subcutaneous injection that effectively limits bleeding episodes due to clotting disorders, offering patients a new treatment option. The approval of the drug marks the first hemophilia treatment on the market in the United States using a user-friendly, pre-filled automatic injection pen and is intended to provide a more convenient and efficient treatment experience for patients, instead of requiring regular injections of proteins that promote blood clotting. Pfizer announced a wholesale acquisition cost (WAC) of $795,600 for Hympavzi. The price is similar to the $3.5 million Pfizer previously charged Beqvez, and comparable to the price CSL and uniQure set for their Hemophilia B gene therapy drug, Hemgenix. Pfizer said the pricing of Hympavzi is "consistent with WAC pricing for currently available preventive treatments for hemophilia A or B in the market," adding that it expects to officially launch the product this quarter. In an October 11 release, Suchitra Acharya, MD, director of Northville Health's Center for Hemostasis and Thrombosis, noted: "The launch of Hympavzi is designed to address an important need for these patients and reduce the burden of current treatments, especially for those who require frequent, time-consuming intravenous infusion therapy regiments, which would be a significant advance." The approval of Hympavzi not only provides new treatment options for hemophiliacs, but also brings innovative treatment models to the healthcare system that are expected to improve patients' quality of life and could have a profound impact on the entire field of hemophilia treatment.

AcquisitionDrug ApprovalGene Therapy

100 Deals associated with Fidanacogene elaparvovec

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hemophilia B	CA	Pfizer Canada ULC	27 Dec 2023

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hemophilia B	Phase 3	TW	Pfizer Inc.	29 Jul 2019
Hemophilia B	Phase 3	SA	Pfizer Inc.	29 Jul 2019
Hemophilia B	Phase 3	KR	Pfizer Inc.	29 Jul 2019
Hemophilia B	Phase 3	JP	Pfizer Inc.	29 Jul 2019
Hemophilia B	Phase 3	TR	Pfizer Inc.	29 Jul 2019
Hemophilia B	Phase 3	BR	Pfizer Inc.	29 Jul 2019
Hemophilia B	Phase 3	AU	Pfizer Inc.	29 Jul 2019

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03861273 (BENEGENE-2, Literature) Manual	Phase 3	Hemophilia B	45	Fidanacogene elaparvovec	(srlgxajvee) = xjyslmrwem rbdaseedst (uodhdfwzjc, 0.57 - 1.98)	Superior	25 Sep 2024
NCT03861273 (BENEGENE-2, Literature) Manual	Phase 3	Hemophilia B	45	Prophylactic factor IX concentrate	(srlgxajvee) = qndzduhesf rbdaseedst (uodhdfwzjc, 1.80 - 7.05)	Superior	25 Sep 2024
NCT03861273 (BENEGENE-2, CTgov)	Phase 3	Hemophilia B	51	PF-06838435 (FIX Prophylaxis)	dxsabrmppu(qxsksyczji) = opgslojnvq ulooxavyfr (nnsrnuveoo, qdximtzcio - mtdmfddial) View more	-	27 Mar 2024
NCT03861273 (BENEGENE-2, CTgov)	Phase 3	Hemophilia B	51	PF-06838435 (PF-06838435)	dxsabrmppu(qxsksyczji) = bzlengkpkq ulooxavyfr (nnsrnuveoo, dcvnpzhazs - gvarwhbhpv) View more	-	27 Mar 2024
NCT03861273 (BENEGENE-2, ASH2023)	Phase 3	Hemophilia B	45	Fidanacogene elaparvovec	daxsbqzkom(bljwnmppod) = jovihjtsum yifnpgrhaz (foubqczuod )	-	09 Dec 2023
NCT03861273 (BENEGENE-2, Corporate Publications) Manual	Phase 3	Hemophilia B	-	fidanacogene elaparvovec	(xegxpgmesv) = ldpczaqmdm yakvybfcza (dznukctafs ) Met View more	Positive	29 Dec 2022
ISTH2020	Phase 1/2	-	-	Fidanacogene elaparvovec	dtjcbnfako(htngcihcpc) = Two patients had non-related SAEs of appendicitis and emergent lumbar discectomy. Both SAEs were managed successfully, without excessive bleeding, and without exogenous FIX treatment. fzmdswbkuh (pzqadjpnzi )	-	12 Jul 2020
NCT02484092 (CTgov)	Phase 2	Hemophilia B	15	SPK-9001 (SPK-9001 (5 x 10^11 vg/kg))	nczdfdfbgp(evisughrja) = sppvebfjkz uymsovefbu (dluqnfbutx, gecpbbkmcr - wigszcfehk) View more	-	19 May 2020
NCT02484092 (CTgov)	Phase 2	Hemophilia B	15	SPK-9001 (SPK-9001 (5 x 10^11 vg/kg) IV Infusion)	qxqjjfthyj(zfputrhnoq) = yfmmujjgpj yoclixmmmx (ydlqzewbsh, hpnyphxots - yxswzsjmyw) View more	-	19 May 2020
NCT02484092 (Pubmed \| Br Dent J) Manual	Phase 2	Hemophilia B	10	Haemophilia B gene therapy	(dpfnqewjeb) = wljejbhwue pqygjudrvf (tlqxryccwb )	Positive	07 Dec 2017

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Fidanacogene elaparvovec

Overview

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Translational Medicine

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