Gene Therapy Database
Summary Information For: AAV-Spark100, FIX-Padua, Fidanacogene elaparvovec (ᴾʳBEQVEZ™), NCT03861273 (Phase 3, BeneGene-2)
AAV-Spark100, FIX-Padua, Fidanacogene elaparvovec (ᴾʳBEQVEZ™), NCT03861273 (Phase 3, BeneGene-2)
Haemophilia B
Pfizer
General Study Information
  • ClinicalTrials.gov Identifier: NCT024840921
  • 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)
  • Active, not recruiting
  • Last Update Posted: 2024-12-03
  • Approval status: According to a supporting document5 on the FDA page, fidanacogene elaparvovec was approved by the FDA on May 20, 2024
  • Males ≥18 y.o. with confirmed diagnosis of hemophilia B (≤2 IU/dL or ≤2% endogenous factor IX)
  • Had ≥50 prior EDs to any FIX protein products
  • A minimum average of 4 bleeding events per year requiring episodic treatment of factor IX infusions or prophylactic factor IX infusions
  • Neutralizing antibodies reactive with AAV-Spark100 above and/or below a defined titre
  • Participated in a gene transfer trial within the last 52 weeks or in a clinical trial with an investigational drug within the last 12 weeks

Bioengineered capsid AAV-Spark1003 / HEK293 cells

Codon-opimized FIX-Padua / FIX-R338L2, 3

The FIX expression cassette3 includes:

  • APOE gene hepatic-control region (APOE-HCR) enhancer and the
  • ​​​​Liver-specific human α1 -antitrypsin (hAAT) promoter

Systemic4

Single dose cohort: 5e11 (45)2

44 of 45 pts. completed at least 15 months2

One-stage SynthASil assay2

Efficacy details

At 15 months, the mean FIX activity was 26.9% (median of 22.9%; range from 1.9% to 119.0%)2

Not yet reported

The ABR 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)2

Not yet reported

Safety Details

No infusion-related serious adverse events observed2

No thrombotic events, development of factor IX inhibitors were observed2

Not yet reported

A total of 28 participants (62%) received glucocorticoids for increased aminotransferase levels or decreased factor IX levels (or both) starting between 11 and 123 days2

A total of 28 participants (62%) received glucocorticoids for increased aminotransferase levels or decreased factor IX levels (or both) starting between 11 and 123 days2

Not yet reported

Not yet reported

A total of 28 participants (62%) received glucocorticoids for increased aminotransferase levels or decreased factor IX levels (or both) starting between 11 and 123 days2

No malignant conditions were observed2

References:
  1. A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B (BENEGENE-2). ClinicalTrials.gov identifier: NCT03861273. Link
  2. Cuker A, Kavakli K, Frenzel L, Wang JD, Astermark J, Cerqueira MH, et al.; BENEGENE-2 Trial Investigators. Gene Therapy with Fidanacogene Elaparvovec in Adults with Hemophilia B. N Engl J Med. 2024 Sep 26;391(12):1108-1118. doi: 10.1056/NEJMoa2302982. PMID: 39321362. Link
  3. George LA, Sullivan SK, Giermasz A, Rasko JEJ, Samelson-Jones BJ, Ducore J, et al. Hemophilia B Gene Therapy with a High-Specific-Activity Factor IX Variant. N Engl J Med. 2017 Dec 7;377(23):2215-2227. doi: 10.1056/NEJMoa1708538. PMID: 29211678; PMCID: PMC6029626. Link
  4. Nathwani AC. Gene therapy for hemophilia. Hematology Am Soc Hematol Educ Program. 2019 Dec 6;2019(1):1-8. doi: 10.1182/hematology.2019000007. PMID: 31808868; PMCID: PMC6913446. Link
  5. Dhillon S. Fidanacogene Elaparvovec: First Approval. Drugs. 2024 Apr;84(4):479-486. doi: 10.1007/s40265-024-02017-4. Epub 2024 Mar 12. PMID: 38472707. Link

AAV, Adeno-associated virus; ABR, Annualized bleeding rate; AEs: adverse events; AIR, Annualized FVIII/FIX infusion rate; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CH, Chromogenic Assay; Co., cohort; DOACs, Direct oral anticoagulants; D, days; EDs, exposure days; FIX, factor IX; FIX-Padua, gain of function FIX variant; FVIII, factor VIII; gc, genome copies; HEK cells, human embryonic kidney cells; IQR, interquartile range; IRR, Infusion-related reaction; NAbs, neutralizing antibodies; OS, One-stage clotting assay; Pop., population; pt., patient/participant; pts., patients/participants; P1, Participant 1; PI, phase I; PBGD, porphobilinogen deaminase; PBMC, peripheral blood mononuclear cells; SAEs, serious adverse events; SFU, spot-forming units; TAC, tacrolimus; ULN, upper limit of normal; VCN, vector copy number; vg, vector genomes; W, weeks; WT, wild type; Y, year