Oxford BioMedica plc biopharmaceuticals and its partner Sanofi announced a positive interim review of the RetinoStat(R) Phase I study in neovascular "wet" age-related macular degeneration (AMD) and the StarGen(TM) Phase I/IIa study in Stargardt disease by the Data Safety Monitoring Board (DSMB); an independent panel of specialists in the fields of ophthalmology, virology and vectorology. RetinoStat(R) and StarGen(TM) were designed and developed by Oxford BioMedica using the Company's proprietary LentiVector(R) gene delivery technology.
Age-related macular degeneration (AMD) is a major cause of blindness affecting an estimated 25 to 30 million people worldwide and the incidence of AMD is expected to triple by the year 2025 (source: AMD Alliance International). Neovascular "wet" AMD accounts for the majority of all severe vision loss from the disease.
RetinoStat(R) delivers two anti-angiogenic genes, endostatin and angiostatin, directly to the retina and aims to preserve and improve the vision of patients through anti-angiogenesis which blocks the formation of new blood vessels. On the basis of pre-clinical data, it is anticipated that RetinoStat(R) may require only a single administration which would give the product a significant advantage in the market over currently available treatments that often require frequent, repeated administration.
DSMB highlights of ongoing RetinoStat(R) Phase I study
- Nine patients treated to date (n=3 at each of dose levels 1, 2 and 3)
- No serious adverse events related to RetinoStat(R) or its method of administration
- Long-term safety profile now up to 18 months post-treatment (dose level 1)
- Successful retinal transduction, as shown by substantial increase in expression and secretion of endostatin and angiostatin proteins measured in the anterior chamber of the eye following a single administration of RetinoStat(R). So far, expression is sustained for up to 12 months post-treatment at dose level 1 (n=3) and up to six months post-treatment at dose level 2 (n=3)
- DSMB support received to proceed to final patient cohort (n=9, confirmatory dose level)
Stargardt disease is the most common juvenile degenerative retinal disease which affects approximately 80-100,000 patients in the US and Europe. The disease is caused by a mutation of the ABCR gene which leads to the degeneration of photoreceptors in the retina and vision loss. StarGen(TM) uses the Company's LentiVector(R) platform technology to deliver a corrected version of the ABCR gene. On the basis of pre-clinical data, it is anticipated that a single application of StarGen(TM) to the retina could potentially either provide long-term or permanent correction. There are currently no approved treatments available for Stargardt disease.
DSMB highlights of ongoing StarGen(TM) Phase I/IIa study
- Eight patients treated at dose level 1 to date (n=4 severe level of disease, n=4 less severe)
- No serious adverse events related to StarGen(TM) or its method of administration
- Long-term safety profile now up to 12 months post-treatment (dose level 1)
- DSMB support received to proceed to third patient cohort (n=4, dose level 2)
John Dawson, Chief Executive Officer of Oxford BioMedica, said, "The continued progress of our ophthalmology portfolio, supported by another positive DSMB review, is encouraging - particularly given that early RetinoStat(R) data demonstrate sustained therapeutic protein expression in the eye following a single administration. The favourable safety profile of our novel ocular gene therapies further supports the wider LentiVector(R) platform safety package with over 33 patients treated to date across the ocular and Parkinson's disease programmes."
The RetinoStat(R) open label, dose escalation Phase I study will enrol 18 patients with "wet" AMD and will evaluate three dose levels to assess safety and aspects of ocular physiology. The study is led by Professor Peter Campochiaro at the Wilmer Eye Institute at Johns Hopkins, Baltimore (USA) and Oxford BioMedica has opened a second clinical site at the Oregon Health and Science University, Portland with Dr Andy Lauer as principal investigator. Further results from this study are expected in Q4 2012.
The StarGen(TM) open label, dose escalation Phase I/IIa study will enrol up to 28 patients and will evaluate three dose levels for safety, tolerability and aspects of biological activity. In the US, the study is led by Professor David Wilson at the Oregon Health and Science University, Portland, Oregon. In France, Professor Jose-Alain Sahel leads the study at Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris. StarGen(TM) has received European and US Orphan Drug Designation which brings development, regulatory and commercial benefits. Further results from this study are expected in Q4 2012.