Recent hemophilia B gene therapy trial using AAV
| Sponsor . | Transgene . | No. of CpG motifs in transgene . | Serotype . | Genome format . | Method of vector delivery . | Dose range (vg/kg) . | Mean stable FIX activity levels . | No. of patients with transaminitis . | Current status . |
|---|---|---|---|---|---|---|---|---|---|
| Avigen/CHOP | Wild-type FIX | 19 | AAV2 | ssAAV | IM | 2e11 to 1.8e12 | Transient at a maximum level of 1.6% | 0 | Closed |
| Avigen/CHOP Coagulin-B | Wild-type FIX | 19 | AAV2 | ssAAV | Intrahepatic artery | 2e11 to 2e12 | Transient with a maximum of 12% | 1/2 at highest dose | Closed |
| St Jude/UCL | Codon-optimized FIX | 0 | AAV8 | scAAV | Systemic | 2e11 to 2e12 | 5.1% | 4/6 patient at highest dose | Closed |
| Takeda (Baxalta; BAX 335) | Codon-optimized FIX + Padua mutation | 99 | AAV8 | scAAV | Systemic | 2e11 to 3e12 | Transient except in 1 patient who had expression of ~20% at last report | 2/6 patients treated at or above 1e12 received steroids in response to ALT elevations and 1 patient received prophylactic steroids. | Closed |
| Spark Therapeutics (SPK-9001, fidanacogene elaparvovec) | Codon-optimized FIX containing the Padua mutation | 0 | AAV- Spark100 | ssAAV | Systemic | 5e11 | 19.8% at 5 years | 3/15 patients | Transitioned to phase 3 with Pfizer |
| uniQure (AMT-060) | Codon-optimized FIX | 0 | AAV5 | ssAAV | Systemic | 5e12-2e13 | 6.9% 5.2% at 5e12-vg/kg dose and 7.2% at 2e13-vg/kg dose at 5 years | 2/5 at highest dose | A new program, AMT-061, that contains the FIX Padua in development with CSL Behring |
| CSL Behring (AMT-061, etranacogene dezaparvovec) | Codon-optimized FIX containing the Padua mutation | ?0 | AAV5 | ?ssAAV | Systemic | 2e13 | 36.9% | 9/54 | Under regulatory review |
| Dimension Therapeutics (DTX101) | Codon-optimized FIX | 96 | AAVrh10 | ssAAV | Systemic | 1.6e12-5e12 | 6.7% | 3/3 at highest dose | Closed |
| Freeline Therapeutics (FLT-180a, verbrinacogene setparvovec) | Codon-optimized FIX containing the Padua mutation | 5 | AAV-S3 synthetic capsid | ssAAV | Systemic | 3.84e11-1.28e12 | 30%-279% | 8/10 | Clinical trials ongoing |
| Belief BioMed (BBM-H901) | Codon-optimized FIX containing the Padua mutation | 0 | AAV843 synthetic capsid | scAAV | Systemic | 5e12 | 36.9% | 2/10 | Clinical trials ongoing |
| Sangamo Bioscience (SB-FIX) | Codon-optimized FIX | Not known | AAV6/zinc finger–mediated targeted integration into the albumin locus in hepatocytes | ssAAV | Systemic | Unknown | Unknown | Closed |
| Sponsor . | Transgene . | No. of CpG motifs in transgene . | Serotype . | Genome format . | Method of vector delivery . | Dose range (vg/kg) . | Mean stable FIX activity levels . | No. of patients with transaminitis . | Current status . |
|---|---|---|---|---|---|---|---|---|---|
| Avigen/CHOP | Wild-type FIX | 19 | AAV2 | ssAAV | IM | 2e11 to 1.8e12 | Transient at a maximum level of 1.6% | 0 | Closed |
| Avigen/CHOP Coagulin-B | Wild-type FIX | 19 | AAV2 | ssAAV | Intrahepatic artery | 2e11 to 2e12 | Transient with a maximum of 12% | 1/2 at highest dose | Closed |
| St Jude/UCL | Codon-optimized FIX | 0 | AAV8 | scAAV | Systemic | 2e11 to 2e12 | 5.1% | 4/6 patient at highest dose | Closed |
| Takeda (Baxalta; BAX 335) | Codon-optimized FIX + Padua mutation | 99 | AAV8 | scAAV | Systemic | 2e11 to 3e12 | Transient except in 1 patient who had expression of ~20% at last report | 2/6 patients treated at or above 1e12 received steroids in response to ALT elevations and 1 patient received prophylactic steroids. | Closed |
| Spark Therapeutics (SPK-9001, fidanacogene elaparvovec) | Codon-optimized FIX containing the Padua mutation | 0 | AAV- Spark100 | ssAAV | Systemic | 5e11 | 19.8% at 5 years | 3/15 patients | Transitioned to phase 3 with Pfizer |
| uniQure (AMT-060) | Codon-optimized FIX | 0 | AAV5 | ssAAV | Systemic | 5e12-2e13 | 6.9% 5.2% at 5e12-vg/kg dose and 7.2% at 2e13-vg/kg dose at 5 years | 2/5 at highest dose | A new program, AMT-061, that contains the FIX Padua in development with CSL Behring |
| CSL Behring (AMT-061, etranacogene dezaparvovec) | Codon-optimized FIX containing the Padua mutation | ?0 | AAV5 | ?ssAAV | Systemic | 2e13 | 36.9% | 9/54 | Under regulatory review |
| Dimension Therapeutics (DTX101) | Codon-optimized FIX | 96 | AAVrh10 | ssAAV | Systemic | 1.6e12-5e12 | 6.7% | 3/3 at highest dose | Closed |
| Freeline Therapeutics (FLT-180a, verbrinacogene setparvovec) | Codon-optimized FIX containing the Padua mutation | 5 | AAV-S3 synthetic capsid | ssAAV | Systemic | 3.84e11-1.28e12 | 30%-279% | 8/10 | Clinical trials ongoing |
| Belief BioMed (BBM-H901) | Codon-optimized FIX containing the Padua mutation | 0 | AAV843 synthetic capsid | scAAV | Systemic | 5e12 | 36.9% | 2/10 | Clinical trials ongoing |
| Sangamo Bioscience (SB-FIX) | Codon-optimized FIX | Not known | AAV6/zinc finger–mediated targeted integration into the albumin locus in hepatocytes | ssAAV | Systemic | Unknown | Unknown | Closed |
IM, intramuscular; scAAV, self-complementary AAV; ssAAV, single stranded AAV.