Oxford BioMedica
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OXB 102 is a gene-based treatment for Parkinson's disease, a chronic degenerative neurological condition. 

OXB-102 (higher potency formulation of OXB-101 (ProSavin®)) scheduled to commence in 2016.

Parkinson’s disease

Parkinson’s disease is caused by the degeneration of nerve cells in part of the brain called the substantia nigra.  This leads the loss of dopamine, a chemical messenger which plays a vital role in the coordination of body movement.  Loss of dopamine causes nerve cells to fire without normal control, leaving patients less able to control their movement, and is responsible for many of the symptoms of Parkinson's disease such as tremor, muscle stiffness or slow physical movements.  The exact cause of the loss of nerve cells in the brain is unclear; however research indicates that it could be a combination of genetic and environmental factors.

Our approach

OXB-102 utilises the LentiVector® platform technology to carry three genes that encode the key enzymes for the synthesis of dopamine. When injected into the appropriate part of the brain, called the striatum, OXB-102 genetically modifies the cells so that they produce dopamine, thereby replacing the dopamine that is lost during the course of the disease. It is anticipated that only a single administration will be required to provide benefit to the patient for a number of years.


In early-stage Parkinson’s disease, levadopa (L-DOPA) tablets are effective in managing the symptoms.  L-DOPA is a chemical building-block which the body converts into dopamine.  However, the body progressively loses its ability to convert L-DOPA to dopamine and its effectiveness is reduced with long-term use. OXB-102 is designed to restore local continuous dopamine release to control symptoms without side effects.

Continuous dopamine release:

Clinical status

In April 2012, Oxford BioMedica announced the successful completion of the ProSavin Phase I/II study. The study met its primary endpoints, demonstrating that ProSavin® is safe, well-tolerated and provides a statistically significant improvement of motor function relative to baseline at six and 12 months post-treatment. These results were subsequently published in The Lancet in January 2014. Following this study the Group decided to evaluate a more potent vector construct, known as OXB-102, to ensure the greatest chance of success in future randomised Phase II studies. The efficacy arm of the OXB-102 non-clinical programme was successfully completed in 2013. Highlights include: Positron Emission Tomography (PET) data analysis demonstrates direct expression of transgenes and that expression following administration of OXB-102 is increased relative to ProSavin®; and behavioural and movement analysis indicates that OXB-102 is at least five-fold more potent than ProSavin®. A non-clinical toxicology and bio-distribution study is ongoing.

In the meantime the Group is evaluating the best way to take OXB-102 forward into clinical studies once the toxicology and bio-distribution study is completed. In April 2014, the Group was awarded a £2.2 million grant under the Technology Strategy Board’s Biomedical Catalyst competition to support the next development phase for OXB-102. In May 2015, Professor Stéphane Palfi MD, PhD presented at the American Association of Neurological Surgeons (AANS) conference the results of the long term (three year) follow up of the 15 Parkinson’s disease patients in the Phase I/II study of ProSavin®. A significant improvement in mean unified Parkinson's disease rating scale (UPDRS) part III motor scores in the off medication compared to baseline in all patients had been observed at six and 12 twelve months. The follow up to date has shown that this improvement has been sustained in the majority of patients for up to three years in this progressively degenerative disease and up to four years in some patients disease.

The data supports the continued development of OXB-102, an enhanced construct of ProSavin®, where pre-clinical studies have shown it to be five to ten times more potent than ProSavin®. LA Phase I/II dose escalation study for OXB-102 has been designed and the study protocol is in the process of being approved by the regulatory authorities. The study could commence in 2017 subject to successfully out-licensing or spinning out the product.

Market opportunity

OXB-102 is a novel approach to the treatment of Parkinson’s disease. Parkinson’s disease affected 2.3 million patients in the seven major markets; US, Japan, UK, France, Germany, Italy and Spain in 2011 and is projected to rise to 2.8 million by 2021 (source: Datamonitor 2012). A patient with Parkinson’s disease progressively loses the ability to make the neurotransmitter dopamine, the mediator of the control of movement. The treatment market for Parkinson’s disease is expected to reach US$3.5 billion by 2018 (source: Visiongain Parkinson’s Disease-World Drug Industry and Market 2014-2024, published 2014).

Proof of concept

Pre-clinical studies in the industry standard in vivo model of Parkinson’s disease have shown that, following a single treatment with ProSavin®, almost complete recovery of movement behaviour was achieved after five to eight weeks.  The therapeutic effect of ProSavin® was statistically significant (p.0.05) after two weeks and was maintained throughout the duration of the pre-clinical studies, with the latest time point being 44 months.

Key publications:
Jarraya et al. Sci Transl Med. 2009 Oct 14;1(2): “Dopamine Gene Therapy for Parkinson’s Disease in a Nonhuman Primate Without Associated Dyskinesia”

In January 2014, The Lancet published the results of Phase I/II for OXB-102.

Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial.

Palfi S, Gurruchaga JM, Ralph GS, Lepetit H, Lavisse S, Buttery PC, Watts C, Miskin J, Kelleher M, Deeley S, Iwamuro H, Lefaucheur JP, Thiriez C, Fenelon G, Lucas C, Brugières P, Gabriel I, Abhay K, Drouot X, Tani N, Kas A, Ghaleh B, Le Corvoisier P, Dolphin P, Breen DP, Mason S, Guzman NV, Mazarakis ND, Radcliffe PA, Harrop R, Kingsman SM, Rascol O, Naylor S, Barker RA, Hantraye P, Remy P, Cesaro P, Mitrophanous KA.

Lancet. 2014 Mar 29;383(9923):1138-46. doi: 10.1016/S0140-6736(13)61939-X. Epub 2014 Jan 10.