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Madhu Davies, Scott Ellis, Nicola Adams, Katie Binley, Michelle Kelleher, Kyriacos Mitrophanous; Lentiviral Gene therapies for wet AMD, Stargardt macula dystrophy and Usher Syndrome 1B : clinical trial updates. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3299.
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Oxford BioMedica currently has three ocular therapies in clinical development that incorporate its proprietary LentiVector® platform which is based on recombinant Equine Infectious Anaemia Virus (EIAV): RetinoStat®, StarGen™ and UshStat®, for the treatment of age-related macular degeneration, Stargardt macula dystrophy and Usher Syndrome 1B respectively. Phase I (RetinoStat®) and Phase I/IIa (StarGen™ and UshStat®) clinical evaluations are currently underway.
The design of the trials for RetinoStat®, StarGen™ and UshStat® consists of a dose-escalation phase followed by an expanded final cohort at the highest safe and tolerated dose. Primarily safety but also signs of clinical benefit will be assessed throughout these trials. Additionally, the secreted nature of the transgenes in the RetinoStat® trial has meant that transgene expression from aqueous tap samples can also be quantified over time at each dose.
The dose-escalation phase of the RetinoStat® trial has been completed. For StarGen™ and UshStat® the dose-escalation phase is in progress. Subretinal administration of all three products has been well tolerated, causing no ocular inflammation or immune responses in any patients to date. There have been no SAEs related to any of the products and all three products have been safe and well tolerated. Transduction of the retina following subretinal injection of RetinoStat® rapidly produced high levels of both transgenes detectable in the aqueous. These levels are substantial, show dose dependence and are persistent out to the longest time point assessed.
Ocular gene therapies based on lentiviral vectors continue to show good safety following subretinal delivery into patients for three different ocular indications. The RetinoStat® gene expression data analysed thus far suggest that the LentiVector® platform is a highly effective system for delivering genes into target retinal cells, resulting in stable and long-term expression.
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