Oxford BioMedica
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ProSavin®

ProSavin® is a gene-based treatment for Parkinson's disease, a chronic degenerative neurological condition. 

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

ProSavin® uses LentiVector® technology to deliver the genes for three enzymes that are required for the synthesis of dopamine. The product is administered locally to the region of the brain called the striatum, where dopamine is needed. ProSavin® converts cells into a replacement dopamine “factory” within the brain, thus replacing the patient's own lost source of the neurotransmitter in a tonic level analogous to natural dopamine supply in the absence of Parkinson’s disease.

Administration:

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.  ProSavin® 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 that a Phase I/II study to assess the safety, efficacy and dose evaluation of ProSavin® in patients with mid-to-late-stage Parkinson’s disease successfully met its primary endpoints. The study evaluated three ascending dose levels of ProSavin® (1x, 2x and 5x) in a total of 15 patients. The primary endpoints were safety and efficacy as measured by improvements in motor function at six months.  ProSavin® has demonstrated a long-term safety profile and all 15 patients showed improvements in motor function at the six-month efficacy endpoint relative to baseline.

Next steps:

Oxford BioMedica is currently evaluating a more potent product construct to ensure the greatest chance of success in future randomised Phase II studies, by increasing the benefit for patients, and to increase the commercial opportunity by offering extended patent protection and a relative reduction in cost of goods.  The non-clinical programme will evaluate improvements in motor function, in addition to Positron Emission Tomography (PET) data to assess dopaminergic activity.

Market opportunity

Parkinson’s disease affected approximately 2.3 million patients in 2011 in the seven major markets (US, Japan, UK, France, Germany, Italy and Spain), projected to rise to 2.8 million by 2021.  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). 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.

Pre-clinical 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 publication: 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”

Facts

30%

In the final patient cohort of the ProSavin® Phase I/II study (n=6 at 5x dose, enhanced administration) average motor function improved by 30%, with a maximum of 41% in one patient at the six month timepoint