Interim Update on ProSavin? Phase I/II Study

RNS Number : 0120U

Oxford Biomedica PLC

15 December 2011

 

Oxford BioMedica Announces Interim Update on ProSavin^® Phase I/II Study in Parkinson's Disease

-- Positive review of all patient cohorts by Data Monitoring Committee --

-- ProSavin^® provides long-term improvement of motor function --

Oxford, UK - 15 December 2011: Oxford BioMedica plc ("Oxford BioMedica" or "the Company") (LSE: OXB), the leading gene-based biopharmaceutical company, today announces new data from its Phase I/II study to assess the safety, efficacy and dose evaluation of ProSavin^® in patients with mid-stage Parkinson's disease (PD).  As part of an interim review, Oxford BioMedica and its clinical experts have analysed the current data set for all 15 patients and there is a pre-recorded webcast available via: http://cache.cantos.com/webcast/static/ec2/4000/5275/9523/9863/Lobby/default.htm. 

Summary of Oxford BioMedica's efficacy analysis of all 15 patients treated:

·      ProSavin^® mediates improvement in UPDRS Part III "OFF" scores¹ in all cohorts at six-month primary efficacy endpoint;

·      Population analysis of cohorts 1-3 indicates that ProSavin^® significantly improves motor function relative to baseline, with statistically significant improvements up to 12 months;

·      ProSavin^® demonstrates efficacy across range of disease severity; and

·      Treatment with ProSavin^® supports average reduction in L-DOPA "equivalent" therapy in all cohorts with signs of a dose-related response - cohort 4 (5x dose) indicates highest level of dopamine provision vs. earlier cohorts

1.     Motor function is assessed according to the Unified Parkinson's Disease Rating Scale (UPDRS) in patients' "OFF" state (i.e. after withdrawal of PD medication).

ProSavin^® has been evaluated in four ascending dose cohorts (1x, 2x and 5x) in a total of 15 patients.  Six patients received the 2x dose, the latter three of which were treated using an enhanced administration procedure which facilitates higher dosing, and six patients received the 5x dose.  The primary efficacy end-point of the Phase I/II trial is the six-month UPDRS assessment and results from all six patients in the fourth (5x dose) cohort are expected in H1 2012.  Results from the latest assessment of all four cohorts have now been verified and reviewed by the study's independent Data Monitoring Committee (DMC).

DMC highlights of all four patient cohorts (n=15):

·      Favourable safety profile with no serious adverse events related to ProSavin^® or the enhanced administration technique;

·      Cohort 4 (5x dose) shows most promising signs of efficacy to date including improved UPDRS Part III "OFF" scores, improved UPDRS Part III "ON" scores² despite a reduction in L-DOPA "equivalent" therapy and a reduced Positron Emission Tomography (PET) scan signal implying a higher level of dopamine provision;

·      Average L-DOPA "equivalent" therapy has either reduced or remained stable in all four cohorts, in what is usually a progressively degenerative disease requiring an increase in dose; and

·      Long-term safety profile 36 months post-treatment (1x dose)

2.     UPDRS in patients' "ON" state (i.e. with medication and when PD symptoms are not present).

Professor Olivier Rascol, Chair of the independent DMC, said: "We are pleased that ProSavin^® and the enhanced administration technique continue to demonstrate a long-term safety profile.  The signals of improvements in motor function with decreased oral dopaminergic therapy observed to date are encouraging, particularly at the 5x dose.  The functional imaging data also suggest possible dopamine provision attributable to ProSavin^® at this dose.  We would support investigation of a further dose escalation for this novel product as part of a Phase II development programme."

Oxford BioMedica and its clinical experts believe that the interim ProSavin^® data set continues to support planning for a sham-controlled Phase II study.  During 2011, the Company has identified and developed an enhanced product construct based on the ProSavin^® dopaminergic enzymes.  The new construct can potentially provide more than a 10-fold increase in dopamine production capacity, allowing further dose escalation without impacting volume or rate of administration.  In addition, the new construct offers extended patent protection and a relative reduction in cost of goods, thus increasing the commercial opportunity for ProSavin^®.  The Company looks forward to six-month results from all six patients in the fourth (5x dose) cohort in H1 2012 and, given the potential of the new construct, will evaluate a strategy to move it into development as part of a Phase II programme.

John Dawson, Chief Executive Officer of Oxford BioMedica, said: "Our pioneering Phase I/II trial is designed to assess the safety of ProSavin^® and provide an indication of efficacy.  We are therefore pleased to see such encouraging improvements across several measures of clinical benefit in patients with an inexorably degenerative disease at this stage of development. 

"Based on our positive analyses to date, independent advice from our Data Monitoring Committee and our discussions with potential partners, we believe that this data set supports exploration of a higher dose as part of a Phase II programme to ensure the greatest chance of success in randomised studies.  Partnering discussions continue and we look forward to reporting further progress in 2012."

Historic analysis of the Phase I/II study and top-line motor function has focused on individual patient cohorts (as seen in table 1 below).  When treating small numbers of patients, results can vary considerably - particularly in a heterogeneous disease such as Parkinson's disease.  For a more comprehensive and informative analysis of the current data set, please refer to the pre-recorded webcast.

Table 1: Summary of independently verified improvements in motor function to date

Cohort3	Dose	Admin. method	3 months (UPDRS)	6 months (UPDRS)		1 year (UPDRS)	2 years (UPDRS)
1, n=3	1x	Original	Mean 27% Max. up to 30%	Mean 30% Max. up to 48%		Mean 29% Max. up to 44%	Mean 20% Max. up to 30%
2, n=3	2x	Original	Mean 28% Max. up to 53%	Mean 34% Max. up to 53%		Mean 29% Max. up to 56%	Mean 27% Max. up to 47%
3, n=3	2x	Enhanced	Mean 26% Max. up to 52%	Mean 43% Max. up to 61%		Mean 28% Max. up to 48%	-
4, n=6	5x	Enhanced	Mean 26% Max. up to 49%	Mean 24% Max. up to 31%	n=3 of 6	-	-

3.     Cohorts 3 and 4 had more severe mean baseline UPDRS scores than previous cohorts, therefore some patients may also have to overcome other features of PD e.g. muscle weakness, rigidity etc.

- Ends -

For further information, please contact:
Oxford BioMedica plc: Lara Mott, Head of Corporate Communications	Tel: [phone]
Media Enquiries: Mary Clark/Emma Thompson/Claire Dickinson M:Communications	Tel: [phone]

Notes to editors

1. Oxford BioMedica

Oxford BioMedica plc (LSE: OXB) is a biopharmaceutical company developing innovative gene-based medicines and therapeutic vaccines that aim to improve the lives of patients with high unmet medical needs.  The Company's technology platform includes a highly efficient LentiVector^® gene delivery system, which has specific advantages for targeting diseases of the central nervous system and the eye; and a unique tumour antigen (5T4), which is an ideal target for anti-cancer therapy.  Through in-house and collaborative research, Oxford BioMedica has a broad pipeline with current partners and licensees including Sanofi, Pfizer, GlaxoSmithKline, MolMed, Sigma-Aldrich, Biogen Idec, VIRxSYS, Emergent BioSolutions and ImaginAb.  Further information is available at www.oxfordbiomedica.co.uk.

2. LentiVector^® gene delivery technology

Oxford BioMedica's LentiVector^® gene delivery technology is one of the most advanced gene delivery systems currently available, which has many applications in product development and discovery research.  It is the system of choice for gene-based treatments addressing chronic and inherited diseases.  Oxford BioMedica has established a dominant intellectual property estate in the field of lentiviral-vector mediated gene delivery through its in-house research and from work conducted by the Company's co-founders at Oxford University.

3. Parkinson's disease

Parkinson's disease affects approximately 1.5 million patients in the seven major markets (US, Japan, UK, France, Germany, Italy and Spain) which is projected to rise to 1.7 million by 2019.  None of the current treatments provide long-term relief from symptoms, yet, by 2019, sales of these treatments could exceed US$2.8 billion in the seven major markets (source: Datamonitor, Dec-2010).  ProSavin^® has the potential to address a major unmet medical need in Parkinson's disease, offering long-lasting benefit from a single administration with an excellent safety profile.  The product could therefore also significantly reduce the social care burden that is associated with the mid to late-stage of disease.

4. ProSavin^®

ProSavin^® uses the Company's LentiVector^® gene delivery technology to deliver the genes for three enzymes - AADC (aromatic amino acid decarboxylase), TH (tyrosine hydroxylase) and CH1 (GTP-cyclohydrolase 1) - that are required for the synthesis of dopamine.  These genes re-programme transduced cells to manufacture and secrete dopamine.  The product is administered locally to the region of the brain called the striatum, converting cells into a replacement dopamine factory within the brain, thus replacing the patient's own lost source of the neurotransmitter.  ProSavin^® has the potential to address an unmet medical need in Parkinson's disease, offering long-lasting benefit from a single administration with an excellent safety profile.

 

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