-- Longer term follow-up indicates modest efficacy in primary and related endpoints --
The additional, protocol-prescribed analyses reported today focused on further analyses of the data from the 30 subjects who continued to be evaluated under double-blind conditions for up to 18 months which indicate increasing effects of CERE-120 over time. A clinically modest but statistically significant treatment effect in the primary efficacy measure (UPDRS motor off; p=0.025), as well as similar effects on several more secondary motor measures (p<0.05), were seen at the 18 month endpoint. Not a single measure similarly favored sham surgery at either the 12 month or 18 month time points. Additionally, CERE-120 appears safe when administered to advanced Parkinson's disease patients, with no significant concerns related to the neurosurgical procedure, the gene therapy vector, or the expression of neurturin in the Parkinson's disease brain.
The company also reported the results of analyses of neurturin gene expression in the brains from two CERE-120 treated subjects who died of causes unrelated to treatment. These analyses revealed that CERE-120 produced clear evidence of neurturin expression in the targeted putamen but no evidence for transport of this protein to the cell bodies of the degenerating neurons, located in the substantia nigra. In addition to the known cell loss in Parkinson's disease, these findings suggest that deficient axonal transport in degenerating nigrostriatal neurons in advanced Parkinson's disease impaired transport of CERE-120 and/or neurturin from putaminal terminals to nigral cell bodies, reducing the bioactivity of CERE-120. The data were presented today at the American Society of Gene Therapy Meeting in
"While we were disappointed that our initial analysis of the data from this trial did not demonstrate a benefit of CERE-120 in the primary endpoint at 12 months, we are greatly encouraged by both the results of these protocol-prescribed analyses in patients who remained blinded for up to 18 months, as well as by the insight we gained," stated Dr. Bartus. "Collectively, these data suggest that CERE-120 is indeed exerting a unique and potentially important biological effect on the degenerating dopamine neurons in moderately advanced Parkinson's disease patients but that the inability of these neurons to efficiently transport neurturin back to their cell bodies compromises and delays the neurotrophic effects of neurturin in a manner that had not been anticipated. Importantly, we believe that we can overcome the transport problems of these degenerating neurons by modifying the dosing paradigm to also directly target their cell bodies in the substantia nigra with CERE-120."
"We remain optimistic that CERE-120 has the potential to significantly improve the treatment of advanced Parkinson's disease patients," stated
About Phase 2 Trial of CERE-120
Ceregene's Phase 2 trial was a double-blind, controlled clinical trial that completed enrollment of 58 patients with advanced Parkinson's disease in
About CERE-120 and its Application to Treating Parkinson's Disease
CERE-120 is composed of an 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 normal function. Neurturin is a member of the same protein family as glial cell-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 has been 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. The cell bodies for these same neurons are located in a different area of the brain, called the substantia nigra. Once CERE-120 is delivered to the brain, it provides stable, long-lasting expression of neurturin in a highly targeted fashion. Genzyme Corporation (Nasdaq: GENZ) has licensed the ex-North American rights for the development and commercialization of CERE-120 from Ceregene, an agreement that was announced in
About Parkinson's Disease
Parkinson's disease is a progressive movement disorder that affects a million people in
Ceregene, Inc. is a
Contacts: Jeffrey M. Ostrove, Ph.D. President and CEO Ceregene, Inc. (858) 458-8808
SOURCE Ceregene, Inc.