Ceregene, Inc., announced today that CERE-120, a gene therapy product in development for the treatment of Parkinson's disease, was well tolerated and appeared to reduce symptoms by approximately 40% (p<0.001), as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) motor "off" score, in an open-label Phase 1 study in 12 patients with advanced disease. Initial results of the study were presented by Dr. William J. Marks Jr., principal investigator of the study and associate professor of Neurology at the University of California, San Francisco (UCSF) today at the American Neurological Association annual meeting in Chicago.
The study was authored by: Dr. Jill Ostrem, UCSF neurologist; Dr. Philip Starr, PhD, and Dr. Paul Larson, who conducted the neurosurgery at UCSF; neurologist Dr. Leo Verhagen, with neurosurgeon Dr. Roy Bakay, at Rush University Medical Center.
The study was supported in part by a grant from The Michael J. Fox Foundation for Parkinson's Research. Based on the initial results, the Foundation today announced plans to partially fund a Phase 2 study with a $1.9 million grant
"We were encouraged by the results of the Phase 1 trial," said Deborah W. Brooks, president and CEO of The Michael J. Fox Foundation. "Based on these and on the intriguing efficacy observations, we're eager to continue to support research in Phase 2 that will more definitively assess the potential of CERE-120 to treat PD."
CERE-120 is comprised of an adeno-associated virus (AAV) vector carrying the gene for neurturin (NTN), a naturally occurring protein, whose role is to keep dopamine-secreting neurons alive and functioning normally. All 12 patients enrolled in the study underwent stereotactic neurosurgery to deposit CERE-120 into their putamen. The putamen is a region of the brain that undergoes degeneration and reduced dopamine production in Parkinson's disease patients and this has been closely linked to the major motor deficits in these patients.
All patients entered in the trial were judged to have inadequate control of their disease with standard levadopa therapy and were otherwise potential candidates for additional treatment interventions such as deep brain stimulation (DBS) surgery.
CERE-120 was delivered at 2 different doses, with patients receiving the low dose demonstrating approximately 40% improvement in UPDRS motor "off" scores by 9 months and patients receiving the 4-fold higher dose showing a similar effect 3 months sooner. Patients also demonstrated a 50% reduction in hours of "off" time (i.e., time when normal Parkinson's medication was ineffective and symptoms were troubling to the patient) and a doubling of good quality "on" time without dyskinesias (i.e., time when a patient is functioning well) according to self-reported diaries.
NTN (neurturin) is a member of the same protein family as glial cell-derived neurotrophic factor (GDNF) and the two molecules have similar pharmacological properties. GDNF has previously been tested in Parkinson's disease patients. Ceregene owns exclusive technology and product rights to CERE-120.
"Targeted delivery of the trophic factor neurturin is a compelling approach to treating Parkinson's disease," said Dr. Marks. "The safety data and preliminary efficacy data that we have seen in this Phase 1 study are encouraging. Clearly, a larger-scale study is warranted."
According to Dr. Marks, existing treatments for Parkinson's disease treat symptoms only, and for only a limited period of time. "Patients with Parkinson's disease urgently need therapeutic approaches that not only improve symptoms and function, but also have the ability to modify the underlying disease itself in a favorable manner," he said.
In addition to Dr. Marks, the study was authored by: Dr. Jill Ostrem, UCSF neurologist; Dr. Philip Starr, and Dr. Paul Larson, who conducted the neurosurgery at UCSF; neurologist Dr. Leo Verhagen with neurosurgeon Dr. Roy Bakay, at Rush University Medical Center in Chicago; and Raymond T. Bartus, PhD, who led the clinical and preclinical development of CERE-120 at Ceregene.
"The planned Phase 2 trial will be a randomized controlled trial involving approximately 50 patients, and is designed to test if the efficacy we have seen in our initial Phase 1 trial will hold up in a controlled study," stated Jeffrey M. Ostrove, PhD, president and CEO of Ceregene.
Eight medical centers will participate in the Phase 2 study: Baylor College of Medicine, Duke University, Orgeon Health Sciences University, University of Alabama at Birmingham, University of Pennsylvania and Mount Sinai College of Medicine. UCSF and Rush will also be participating.
"The Phase 1 data reported today affirms that the functioning of CERE-120 closely resembled its performance in preclinical studies both in terms of its overall safety as well as its possible efficacy," noted Raymond T. Bartus, PhD, Ceregene's chief operating officer. "The development of growth factors as a treatment for neurodegenerative diseases has been hampered by the difficulty of delivering them specifically to the targeted areas that need their neuroprotective properties. We believe our programs increasingly demonstrate that gene transfer may represent a safe and effective means of solving this age-old problem," said Raymond Bartus.
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