Oxford, UK - 15 October 2009: Oxford BioMedica, a leading gene therapy company, announced today new data from the ongoing Phase I/II trial of ProSavin, its novel gene therapy for the treatment of Parkinson’s disease. All patients treated at the second dose level have completed their six-month assessments and have shown further improvement in motor function (UPDRS III ‘OFF’ score). The maximum improvement was 53% and the average was 34% relative to patients’ pre-treatment motor function. The Principal Investigator, Professor Stéphane Palfi of the Henri Mondor Hospital in Paris, will present interim results from the trial at the European Society of Gene & Cell Therapy Annual Congress, being held in Hannover, Germany, on 21-25 November 2009.
Also announced today is the publication of pivotal preclinical studies of ProSavin, which were conducted with collaborators from the CEA/Inserm Molecular Imaging Research Centre (MIRCen), the University of Paris XII and the Henri Mondor Hospital, a member of the Assistance Publique Hôpitaux de Paris (APHP), in France. The findings were published in the 14 October issue of the interdisciplinary journal, Science Translational Medicine (http://www.sciencemag.org/). The preclinical model used for these studies simulated severe Parkinson’s disease by inducing selective degeneration of dopamine-producing neurons, which decreased dopamine to 27% of normal concentrations. The results showed that: · ProSavin was safe and significantly increased dopamine production from 27% to 47% of normal concentrations (p < 0.05) without the addition of L-DOPA therapy. Overall disease severity was significantly reduced by ProSavin after six weeks (p < 0.05) · ProSavin provided sustained recovery of motor function and behaviour over the 12-month study, which was maintained throughout a follow-up period that concluded after 44 months. Movement and posture were significantly improved after two weeks (p < 0.05), reaching 77% and 85% of respective normal levels · In a study of ProSavin versus oral L-DOPA therapy, both treatments produced a similar correction of disease symptoms. However, the ProSavin group showed no dyskinetic side-effects, whereas L-DOPA therapy induced significant dyskinesias after two weeks (p < 0.05) · To mimic the clinical condition of patients receiving L-DOPA therapy after ProSavin treatment, the preclinical groups were challenged with acute systemic administration of dopaminergic agents. Both the ProSavin arm and also a normal healthy group showed no signs of significant dyskinesias, whereas the control arms displayed debilitating dyskinetic movements following acute dopaminergic challenge (p < 0.05) · Another study mimicked the Phase I/II setting of treating patients with dyskinetic side-effects caused by long-term L-DOPA therapy.In the preclinical model, following an extended period of L-DOPA therapy, the addition of ProSavin maintained motor function recovery with a 44% lower daily dose of L-DOPA, which reduced dyskinesias by up to 60% Overall, these preclinical data suggest that ProSavin may offer significant benefit in the clinical setting, treating the primary symptoms of Parkinson’s disease as well as reducing the severe side-effects of long-term L-DOPA therapy. These conclusions are supported by initial data from human clinical trials.
In December 2007, Oxford BioMedica initiated a dose-escalating Phase I/II study of ProSavin in Parkinson’s disease patients experiencing reduced benefit on L-DOPA or equivalent therapies. This first-in-man study employed a similar neurosurgical technique to the preclinical studies for administering ProSavin directly into a region of the brain called the putamen. Two dose levels have been evaluated to-date in cohorts of three patients per dose. The initial dose level (1x) was based on the safe and efficacious preclinical dose, although it was not scaled for the larger volume of the human putamen. The second dose level represented a cautious, small increment in dose at two-fold higher (2x) than the first dose. At both dose levels, ProSavin was safe and well tolerated with no serious adverse events and no evidence of immunotoxicity. All patients have shown improved motor function and quality of life, and have maintained or reduced their L-DOPA or equivalent medication, whereas daily doses would normally be expected to increase over this period as the disease progresses.
Recent data from the second cohort have shown further improvement in patients’ motor function at six months. The maximum improvement was 53% and the average was 34% relative to baseline, which would be broadly equivalent to Deep Brain Stimulation (DBS) if confirmed in placebo-controlled studies. Even with comparable efficacy to DBS, ProSavin would represent a significant advance, given its simpler administration with no hardware, and its potential to enhance patients’ quality of life and suppress the complications caused by oral L-DOPA therapy.
Despite these promising results, the excellent safety profile of ProSavin justifies further dose escalation. Allometric scaling of the highly efficacious preclinical dose approximates to a human dose that is five-fold higher (5x) than the initial dose. Oxford BioMedica is seeking regulatory approval to escalate directly to a 5x dose level using a modified administration procedure that requires fewer needle tracks and thus reduces the surgery time. Both the study’s Data Monitoring Committee and the Company’s Scientific Advisory Board support this strategy. Enhancing the efficacy of ProSavin and reducing the surgery time could accelerate the overall development timelines and expand the market opportunity.
Professor Stéphane Palfi commented on today’s news: “The preclinical proof-of-concept studies together with clinical data from the first two dose levels in the Phase I/II study suggest that ProSavin may provide sustained and meaningful benefit to patients and could reduce or eliminate the debilitating complications associated with oral dopamine replacement therapy. In the initial indication of moderate to late-stage Parkinson’s disease, ProSavin potentially offers significant advantages to the current alternatives of Deep Brain Stimulation or mechanical delivery of continuous dopamine.”
John Dawson, Oxford BioMedica’s Chief Executive Officer, added: “The recent data from the Phase I/II study provide further evidence that ProSavin is effective at the current dose levels. With its excellent safety profile, we have the opportunity to escalate to a higher dose, which could be even more effective. This would enhance the product’s value and could accelerate its development. We look forward to the presentation of interim clinical results at the upcoming ESGCT Congress. Furthermore, the publication of our ground-breaking preclinical results in a leading journal raises the profile of ProSavin within the medical community and pharmaceutical industry as we prepare for larger studies and negotiate with prospective partners.”
