Ceregene, Inc., a biotechnology company, has reported additional efficacy data from a secondary analysis of its double-blind, randomized, controlled phase IIb clinical study of CERE- 120 (AAV-neurturin). CERE-120 is a gene therapy product designed to deliver the neurotrophic factor neurturin, for Parkinson's disease.
This exploratory analysis identified a more robust response to CERE-120 in Parkinson's patients diagnosed within five years prior to treatment relative to those diagnosed 10 years or more (p<.005), as measured by change from baseline on the Unified Parkinson's Disease Rating Scale or (UPDRS) motor-off, the primary endpoint for this study. Previously Ceregene reported that the primary endpoint (UPDRS) was not met for the overall study population, although one of the 3 prescribed ‘key secondary endpoints' (Diary- hours off) did demonstrate statistical significance and no safety issues were identified. In addition to CERE-120 favorably impacting the UPDRS motor-off scale in patients treated within five years of diagnosis, additional exploratory analyses revealed similar improvement for the same patients in other important Parkinson's disease measurements, including the PDQ-39 (a measure of quality of life) and patient's daily diaries (computing hours "on without troubling dyskinesias").
Raymond T Bartus, Ph.D., executive vice president and chief scientific officer of Ceregene stated: "The concept that earlier-stage patients may respond better to neurotrophic factor therapies such as CERE-120 is consistent with the field's long-standing appreciation for their mechanism of action, as well as more recent information derived from autopsy brain tissue donated by Parkinson's disease patients. While a number of practical considerations will have to be addressed in order to design and execute clinical trials that enroll only early-stage patients, this additional exploratory analysis adds further empirical support that the concept deserves serious consideration."
These and other efficacy and safety data related to the CERE-120 programme were presented, at the American Society for Gene and Cell Therapy annual meeting. The title of Dr Bartus' talk was: "CERE-120 (AAV2- neurturin) for the treatment of Parkinson's disease: Experience from 4 clinical trials and human autopsy data".
During its 12-year history, Ceregene has established leadership positions in the fields of gene therapy and neurotrophic factors for the treatment of neurodegenerative diseases. In addition to publishing 24 peer-reviewed scientific publications describing novel nonclinical and clinical findings in those fields, the company has safely dosed a total of over 100 patients in two clinical programmes: CERE-120 (AAV-NRTN) for Parkinson's disease and CERE-110 (AAV-NGF) for Alzheimer's disease. A randomized, controlled phase II study of CERE-110 for Alzheimer's is continuing. It is fully enrolled and financially supported in large part by a grant from the NIH, with top line data expected by late 2014. In addition to the Parkinson's and Alzheimer's programs, Ceregene has conducted extensive preclinical work with CERE-120 for Huntington's disease, as well as another gene therapy/neurotrophic factor product (AAV-NT4) for blinding ocular diseases (such as Retinitis Pigmentosa, macular degeneration, diabetic retinopathy and glaucoma) and yet another (AAV-IGF1) for Lou Gehrig's disease (ALS). Cergene is currently evaluating strategic alternatives to advance its AAV gene therapy and neurotrophic factor platforms. This study was partially funded by a grant from The Michael J. Fox Foundation for Parkinson's Disease Research.
CERE-120 is composed of a harmless adeno-associated virus (AAV) vector carrying the gene for neurturin, a naturally occurring protein known to repair damaged and dying dopamine-secreting neurons, keeping them alive and restoring function. Neurturin is a member of the same protein family as glial cell line-derived neurotrophic factor (GDNF). The two molecules have similar pharmacological properties and both have been shown to benefit the midbrain dopamine neurons that degenerate in Parkinson's disease. Degeneration of these neurons is responsible for the major motor impairments of Parkinson's disease. CERE-120 is delivered by stereotactic injection to the terminal fields (i.e., the ends of the degenerating neurons), located in an area of the brain called the putamen, as well as the cell bodies for these same neurons, located in a different area of the brain, called the substantia nigra. Once CERE-120 is delivered to the brain, it provides stable, controlled and highly targeted neurturin expression for years following a single injection, confirmed in both animal and human studies.
Parkinson's disease is a progressive movement disorder and its main symptoms are stiffness, tremors and slowed movements and gait, are caused by a loss of dopamine-containing nerve cells in the substantia nigra, which project their axons to the putamen.
Ceregene, Inc. is focused on the development of nervous system growth factors (neurotrophic factors) as treatments for neurodegenerative and retinal disorders using gene transfer for their delivery.