TABLE 3.
Clinical trials of gene therapy for hemophilia A and B
| Sponsor | Serotype | Transgene | Enrollment | Start Date | % of Normal | ABR | Duration | ALT ↑ | ↓Expr With ALT↑ |
Statusb Phase (*abstract form) |
|---|---|---|---|---|---|---|---|---|---|---|
| Hemophilia B Trials: rAAV Vector | ||||||||||
| Avigen/CHOP62 | rAAV2 | FIX‐WT | 4 | 08/07 | 12a | 1/2 | 1/2 | NCT00515710; completed; LTFU | ||
| UCL/SJCRH87 | rAAV2/8 | FIX‐WT | 14 | 02/22/10 | 5.1 | 1.5 (−90%) | >3 y | 4/6 | 4/6 | NCT00979238; active (NR); Ph1 |
| Takeda (Shire)47, 90 | rAAV8 (BAX 335) | FIX‐Padua | 8 | 02/11/13 | 2.8–45.3 | N/A | >4 y | 8/8 | 7/8 | NCT01687608; active (NR); Ph1, 2 |
| Spark/Pfizer117 | Spark100 (SPK9001) | FIX‐Padua | 15 | 11/15 | 33 | 0.4 (−96%) | 2/10 | 2/10 | NCT02484092; completed; Ph2 | |
| Pfizer | Spark100 (SPK9001) | hFIX‐Padua | 20 (est) | 06/22/17 | NCT03307980; recruiting; LTFU of NCT02484092 | |||||
| Pfizer | Spark100 (SPK9001) | hFIX‐Padua | 55 (est) | 07/29/19 | NCT03861273; recruiting; Ph3 | |||||
| uniQure110, 118 | rAAV5 (AMT−160) | FIX‐WT | 10 | 06/10/15 | 5.1–7.5 | 0‐3.3 (−77%–100%) | >4.5 y | 3/10 | 0/10 | NCT02396342; completed; Ph1, 2* |
| uniQure119 | rAAV5 (AMT−061) | hFIX‐coPadua | 54 | 06/27/18 | 37.2 | (−83%) | 26 wk | 7/54 | N/A | NCT03569891; active (NR); Ph3* |
| uniQure120 | rAAV5 (AMT−061) | hFIX‐coPadua | 3 | 07/24/18 | 47 | 0 (−100%) | 26 wk | 3/3 | 0/3 | NCT03489291; active (NR); Ph2, dose confirmation |
| Dimension/Ultragenyx93 | rAAV‐rh10 | co‐hFIX WT | 6 | 01/17 contin | 6.7 | 3/3 | 3/3 | NCT02971969; active (NR); LTFU | ||
| UCL/Freeline94, 95 | AAVS3 (FLT180a) | FIX‐(R338L) Padua | 24 (est) | 12/05/17 | 44‐190 (n = 6, 26 wk) | 0 | 26 wk−3 y | 2/8 | NCT03369444; recruiting; Ph1, 2* | |
| Freeline | AAVS3 (FLT180a) | FIX‐(R338L) Padua | 10 | 07/10/18 | NCT03641703; recruiting; Ph1, 2; LTFU | |||||
| China IHBDHT | rAAV/BBM‐H901 | FIX | 9 (est) | 10/16/19 | NCT04135300; recruiting; N/A | |||||
| Takeda (Shire) | rAAV8 (SHP648) | FIX‐Padua | 21 (est) | 05/13/20 | NCT04394286; suspended; Ph1, 2 | |||||
| Hemophilia B Trials: Lentiviral Vector | ||||||||||
| SGIMI | LV‐FIX (YUVA‐GT‐F901) | FIX | 10 (est) | 06/01/20 | NCT03961243; not yet recruiting; Ph1 | |||||
| Hemophilia A Trials: rAAV Vector | ||||||||||
| BioMarin96, 121 | rAAV5 (BMN270) | H(BDD)‐FVIII‐SQ | 15 | 08/01/2015 | 4‐100 (cohort 3, 3y)121 | 0.8 (−95%)98 | 4 y | 7/7 | 1/7 | NCT02576795; active (NR); Ph1, 2 |
| BioMarin122 | rAAV5 (BMN270) | H(BDD)‐FVIII‐SQ | 134 | 12/19/17 | 43 | 0.8 (n=112) | 52 wk | NCT03370913; active (NR); Ph3 | ||
| BioMarin | rAAV5 (BMN270) | H(BDD)‐FVIII‐SQ | 1 | 03/14/18 | NCT03392974; active (NR); Ph3, 1‐arm dose | |||||
| BioMarin | rAAV5 (BMN270) | H(BDD)‐FVIII‐SQ | 10 (est) | 04/03/18 | NCT03520712; enrolling by invitation; with anti‐AAV5 antibodies; Ph1, 2 | |||||
| BioMarin | rAAV5 (BMN270) | H(BDD)‐FVIII‐SQ | 20 (est) | 11/10/20 | NCT04323098; active; Ph3 | |||||
| BioMarin | rAAV5 (BMN270) | H(BDD)‐FVIII‐SQ | 20 (est) | 12/25/20 | NCT04684940; active; Ph1, 2 | |||||
| Spark |
Spark200/ LK03 (SPK−8011) |
BDD‐FVIII | 30 (est) | 01/26/17 |
5.2–19.8 (n=5)99 (5 × 1011/1 × 1012 vg/kg) |
0.4, 0, 0.4, 3.6, 0.5 (−91%)99 |
>2 y99 | 3/14 | NCT03003533; recruiting; Ph1, 2, dose finding* | |
| Spark |
Spark200/ LK03 (SPK−8011) |
BDD‐FVIII | 100 (est) | 08/14/18 | NCT03432520; enrolling by invitation; LTFU inhibitors | |||||
| Spark123 | (SPK−8016) | BDD‐FVIII | 30 (est) | 01/30/19 | 6.2‐21.8 (n=4) | 0‐2.4 (−85%) | 1–1.5 y | 0/4 | N/A | NCT03734588; active (NR); Ph1, 2, dose finding; inhibitors and non‐inhibitors* |
| Bayer/Ultragenyx124 | rAAV hu37 | BDD‐FVIII | 30 (est) | 11/07/18 | 1‐70 (n=6) | N/A | 30 wk−1.5 y | 3/6 | NCT03588299; recruiting; Ph1, 2* | |
| Pfizer | rAAV2/6 (PF−07055480/SB−525) | BDD‐FVIII | 63 (est) | 08/18/20 | NCT04370054; recruiting; Ph3 | |||||
| Pfizer101 | rAAV2/6 (SB−525) | BDD‐FVIII | 11 | 06/26/17 | 70.4 (n=5; cohort 4) | N/A | 1 y | 10/11 | 1/5 (cohort 4) | NCT03061201; active (NR); Ph2* |
| Takeda (Shire)125 | rAAV8 (TAK−754) | BDD‐FVIII | 12 (est) | 3/31/18 | 1–70 (n=4) | 1.25 (n=4) | 1 y | 4/4 | N/A | NCT03370172; active (NR); Ph1, 2* |
| ASC Therapeutics | rAAV | BDD‐FVIII | 12 (est) | 07/21 (est) | NCT04676048; not yet recruiting; Ph1, 2 | |||||
| UCL | rAAV2/8 | FVIII‐V3 | 18 (est) | 06/14/17 | NCT03001830; recruiting; Ph1 | |||||
| Hemophilia A Trials: Lentiviral Vector | ||||||||||
| Expression26 | CD68‐ET3 | BDD‐hFVIII | 7 (est) | 02/21 (est) | NCT04418414; not yet recruiting; Ph1 | |||||
| MCW/Hari | Pleightlet (MUT6) | BDD‐FVIII | 5 (est) | 04/29/20 | NCT03818763; recruiting; Ph 1 | |||||
| SGIMI | NHP/TYF | FVIII (YUVA‐GT‐F801) | 10 (est) | 06/01/20 | NCT03217032; not yet recruiting; Ph 1 | |||||
Abbreviations: AAV, adeno‐associated virus; ABR, annualized bleed rate; ALT, alanine transaminase; BDD‐FVIII, B‐domain–deleted–factor VIII; CHOP, Children’s Hospital of Philadelphia; contin, continuing; engi, engineered; est, estimate; expr, expression; FIX‐WT, factor IX wild type; IHBDHT, Institute of Hematology & Blood Diseases Hospital Tianjin; LTFU, long‐term follow‐up; MCW, Medical College of Wisconsin; N/A, not applicable; NR, not recruiting; Ph, phase; rAAV, recombinant adeno‐associated virus; SGIMI, Shenzhen Geno‐Immune Medical Institute; SJCRH, St. Jude Children’s Research Hospital; UCL, University College London; ZFN, zinc finger nuclease.
One patient had 12% peak activity that declined to <1% after immune response.
Status determined by ClinicalTrials.gov as of June 2020.
Preliminary data, not peer‐reviewed; to be interpreted with caution.