Gene-based treatment for Parkinson's disease
Status: Phase I/IIa study in preparation
Parkinson’s disease is caused by the degeneration of nerve cells in part of the brain, the substantia nigra. This leads to the loss of dopamine, which causes nerve cells to activate without normal control and leaves patients with symptoms such as tremor, muscle stiffness or slow physical movements. The cause of the nerve cell loss is unclear; however research indicates it is likely a combination of genetic and environmental factors.
OXB-102 is a second-generation gene therapy, which utilises Oxford BioMedica’s LentiVector® platform technology to deliver three genes that encode key dopamine synthesis enzymes. When injected into the brain’s striatum, OXB-102 genetically modifies cells to produce dopamine, replacing that which is lost during the course of the disease. Unlike current drug treatment, which loses efficacy with long-term use, OXB-102 is designed to provide patient benefit for a number of years following a single administration.
Proof of concept
Pre-clinical studies in the industry standard in vivo model of Parkinson’s disease show a single treatment of the first generation product, OXB-101 (also named ProSavin®), resulted in almost complete movement recovery after five to eight weeks. The therapeutic effect was statistically significant (p=0.05) after two weeks, and the therapeutic effect was maintained throughout a 44-month follow-up.
Oxford BioMedica has successfully completed an OXB-101 Phase I/II study, which met its primary endpoint. The results, which were published in the Lancet, demonstrate favourable safety and tolerability and a statistically significant improvement of motor function six and 12 months post-treatment. Ongoing follow up shows this improvement has been sustained in the majority of patients for up to four years, despite the progressively degenerative nature of the disease.
Subsequent pre-clinical studies with the more potent vector construct OXB-102 are also complete. These demonstrate direct transgene expression, which is increased relative to OXB-101, with behavioural and movement analysis indicating at least five-fold greater potency. Oxford BioMedica is working on the regulatory approval for a planned three cohort phase I/II study to be conducted in Cambridge and London, Uk and Paris, France.
Parkinson’s disease is an area of significant unmet medical need, presenting a major market opportunity. The disease affected 2.3 million patients in the US, Japan, UK, France, Germany, Italy and Spain in 2011, with the treatment market expected to reach US$3.5 billion in 2018.
Gene therapy for Stargardt disease
Licensed to Sanofi: Phase II ongoing
Stargardt disease is the most common degenerative retinal disease in young people, and affects approximately 80-100,000 in the US and EU. The disease is caused by mutation of the ABCR gene, which leads to the degeneration of photoreceptors in the retina causing vision loss.
SAR422459 uses Oxford BioMedica’s LentiVector® technology to deliver a corrected ABCR gene via a single administration directly to the retina, which offers a potentially long-term or permanent correction.
Proof of concept
SAR422459 has demonstrated efficacy in the industry standard pre-clinical model of Stargardt disease, in which a single administration was effective for the whole of the six-month study.
SAR422459 is licensed to Sanofi, which has progressed the product into Phase II development. Oxford BioMedica is entitled to future development milestones and royalty payments on SAR422459.
There are no approved treatments available for Stargardt disease, and other therapeutic approaches do not target its root cause. Consequently, SAR422459 has received European and US Orphan Drug Designation. Oxford BioMedica estimates the market opportunity for SAR422459 totals approximately $500 million.