Clinical Stage and Regulatory Timeline
BMN-307 is an investigational gene transfer therapy intended to deliver its phenylalanine hydroxylase (PAH) gene to the liver tissue for the production of PAH enzyme protein. Biomarin is conducting a Phase 1/2 clinical trial (PHEARLESS) to evaluate the safety and efficacy of AAV-PAH gene therapy in subjects with PKU. On September 2020, Biomarin announced the dosing of the first patients in their clinical studies.Viral Vector and Gene Construct:
AAV5.-Liver-specific promoter- PAH. The PAH gene under the liver tissue-specific promoter that drives the expression in the liver tissue. AAV5 is an adeno-associated virus that has been previously used to deliver the gene into liver tissue and successful transgene expression.
Clinical Phase:
Biomarin is currently conducting a Phase 1/2 (NCT04480567) open-label, dose-escalation study to evaluate the safety and efficacy of BMN307 in PKU subjects with PAH deficiency. The proposed sample size is 100 PKU subject with PAH deficiency for the study.
Outcome Measures
Primary Outcome Measure
- Change from baseline in mean Plasma Phe levels
Secondary Outcome
- Change from baseline in mean Plasma Phe levels
- Change from baseline in dietary protein intake from intact food
- Number of participants with treatment-emergent adverse event
Key Results from Phase 1/2a
First Patient Dosed in September 2020
Efficacy
Not available
Durability:
Not available
Safety: Not available
Serious Adverse Events: N/A
Immunogenicity
Antibody Response:N/A
T cell Response (ELISpot): N/A
Non-Clinical Data Based on 2019 RDDay Presentation
It was reported that AAV5-PAH administration resulted in lifetime correction of Phe level similar to wildtype in the Enu-2(pah knockout) mice and supported the clinical development of BMN 307 program (RDDay2019 Presentation).
Reference
Clinicaltrial.gov
Biomarin Press Release
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