Oxford BioMedica Announces Publication of ProSavin® Phase I/II Study in The Lancet
— Pioneering data published in world-leading, peer-reviewed medical journal —
— ProSavin® has demonstrated favourable safety, tolerability and long-term improvement of motor function in advanced Parkinson’s disease —
Oxford, UK – 10 January 2014: Oxford BioMedica plc (“Oxford BioMedica” or “the Company”) (LSE: OXB), the leading gene-based biopharmaceutical company, today announces the online publication of results from the previously reported ProSavin® Phase I/II study in patients with advanced Parkinson’s disease (PD) in The Lancet. According to the key published findings in The Lancet, ProSavin® has demonstrated a favourable safety profile and a statistically significant improvement in motor function relative to baseline at six and 12 months post-treatment.
The paper, entitled “Long-term safety and tolerability of ProSavin®, a lentiviral vector-based gene therapy for Parkinson’s disease: a dose escalation open label phase I/II trial”, can be accessed via http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)61939-X/fulltext.
The study evaluated three ascending dose levels of ProSavin® (1x, 2x and 5x) in a total of 15 patients with PD. Six patients received the 2x dose, the latter three of which were treated using an enhanced administration procedure. Six patients received the highest 5x dose. Patients were treated at two centres of excellence for neurosurgery: the Henri Mondor Hospital in Paris, France with Professor Stéphane Palfi as Principal and Coordinating Investigator, and at Addenbrooke’s Hospital in Cambridge, UK with Professor Roger Barker as Principal Investigator. The primary endpoints of the Phase I/II study were safety and efficacy as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS) assessment at six months.
Highlights from the Phase I/II study
· Safety:ProSavin® has demonstrated a favourable safety profile with no serious adverse events, related to ProSavin® or the surgical procedure, observed to date.
· Efficacy:A statistically significant improvement in motor function relative to baseline was observed at six and 12 months in all patients. Long-term follow-up data showed favourable tolerability and evidence of continued clinical benefit for up to four years post-treatment. Given the nature of this inexorably degenerative disease, these data are extremely encouraging. However, the magnitude of effects does fall within the placebo range reported in other clinical trials for PD utilising surgical techniques and must therefore be interpreted with caution.
Although it is difficult to assess efficacy in small patient populations, there are indications that the highest 5x dose of ProSavin® provided the greatest level of dopaminergic activity. Specifically, patients in the highest 5x dose cohort demonstrated the greatest mean improvement in motor scores; a consistent reduction in requirement for oral dopaminergic medication; and possible dopamine provision attributable to ProSavin® from functional imaging data.
· Oral dopaminergic medication:Eleven out of 15 patients required a reduction in levodopa equivalent daily dose (LEDD) at 12 months compared to baseline. Of the four patients that did not require a decrease at 12 months, three showed no change and one had a small increase in LEDD compared to baseline. In what is usually a progressively degenerative disease requiring an increase in LEDD, these data are encouraging. The need for LEDD reduction was most evident in the highest 5x dose cohort, in which all six patients experienced an increase in “on-medication dyskinesias” at six weeks post-treatment with ProSavin® resulting in an immediate clinical decision to reduce LEDD. In comparison, only four out of nine patients experienced an increase in “on-medication dyskinesias” at the same time point in the lower dose cohorts.
· Patient diaries:The patient diary data indicate a decrease in the mean time spent in the “OFF” (unresponsive to medications) state and an increase in the “ON” (responsive to medication without dyskinesias, or with non-troublesome dyskinesias) state in 13 out of 15 patients. There was no overall difference between the differently dosed cohorts with respect to this.
· Positron Emission Tomography (PET) data: PET scan functional imaging data were generated in France using the tracer [11C] Raclopride. Dopamine competes with the binding of the PET tracer, therefore the more dopamine produced by ProSavin® the lower the PET signal. The three patients treated at the Paris clinical site, receiving the highest 5x dose of ProSavin®, exhibited a significant decrease in [11C] Raclopride binding potential relative to baseline in the putaminal sub-regions, suggesting a partial restoration of striatal dopamine tone in a dose-related fashion.
John Dawson, Chief Executive Officer of Oxford BioMedica, said: “The ProSavin®Phase I/II study was the first ever trial, worldwide, to directly administer a lentiviral vector-based product to patients, and the long-lasting benefits we have seen to date demonstrate the strong potential of this product and the underlying technology developed by Oxford BioMedica. We are pleased that our research has been recognised by The Lancet; this publication in such a highly regarded peer-reviewed journal highlights the significance of our findings to the Parkinson’s disease community.”
Lead author Professor Stéphane Palfi, Principal and Coordinating Investigator at the Henri Mondor Hospital in Paris, commented: “We are pleased with the results of this early clinical study which indicates that the EIAV lentiviral vector technology has an excellent, long-term safety profile. Patients treated with ProSavin® have exhibited a statistically significant improvement up to a full year after receiving a single administration of ProSavin®. This pioneering study using lentiviral vector technology will certainly pave the way for further clinical developments of ProSavin® and potentially other neurological and ocular disorders.”
Tom Isaacs, President and Co-Founder of The Cure Parkinson’s Trust and person with Parkinson’s disease, said: “The publication of this set of results for ProSavin® is yet another step forward in the quest for improvement of Parkinson’s treatments. Not only does Oxford BioMedica’s approach represent an exciting therapeutic prospect but it also demonstrates the huge promise of gene therapy as a means of permanently tackling a condition over which, currently, we only have the ability to temporarily control symptoms.”
Oxford BioMedica is currently evaluating a more potent formulation of ProSavin®, called OXB-102, to ensure the greatest chance of success in future randomised studies. OXB-102 will also increase the commercial opportunity by offering extended patent protection and a relative reduction in cost of goods. The Company holds regular updates with interested parties and is evaluating the most effective strategy to advance OXB-102 into its next stage of development.