Ceregene Presents Long-term Follow-Up From Trial In Parkinson's Disease
Clinical Trial In Parkinson's Disease
Ceregene presented long-term follow-up data from a Phase 1 clinical trial of CERE-120 in 12 patients with advanced Parkinson's disease. CERE-120 uses gene therapy to deliver the neural growth factor neurturin to the major area of neurodegeneration that occurs in the brains of Parkinson's disease patients. Long-term follow up assessments at 18 and 24 months post treatment, suggest a sustained reduction in Parkinson's symptoms.
It was previously reported that an average of 36 percent (p<0.001) reduction in Parkinson's symptoms was seen 12 months after CERE-120 administration. Of the 12 subjects treated, nine had shown a clinically meaningful reduction in symptoms at 12 months, and the mean improvement of these 'responders' at 12 months was 46 percent. Today it was reported that the eight evaluable responders exhibited a persistent mean improvement in symptoms of 52 percent at their longest time of follow-up (24 months for low-dose cohort and 18 months for high-dose cohort).
More specifically, there was a statistically significant improvement in the primary endpoint compared to baseline (p<0.001) defined as the reduction in Parkinson's symptoms as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) motor "off" score ("motor off" meaning patients were off Parkinson's medication at evaluation time). CERE-120 continues to appear safe and well-tolerated, with no treatment-related or surgically-related serious adverse events reported for any of these patients. These data were presented today at the World Congress of Parkinson's Disease by Raymond T. Bartus, Ph.D., Ceregene's executive vice president of clinical and preclinical R&D and chief operating officer.
The Phase 1 trial was an open-label study conducted in 12 patients with advanced Parkinson's disease at two clinical trial sites -- University of California, San Francisco and Rush University Medical Center in Chicago. William J. Marks Jr., M.D., associate professor of neurology at UCSF, was the principal investigator on the trial. All 12 patients enrolled in the study underwent stereotactic neurosurgery to deliver one of two dose levels of CERE-120 into their putamen -- a region of the brain affected by the degeneration of neurons in Parkinson's disease. Several validated secondary motor endpoints, i.e., timed walking test and Purdue pegboard, which also suggested improvement at 12 months, continued to show improvement at 18 and 24 months.
"We are pleased to see that the statistically significant improvement in motor symptoms seen in the Parkinson's patients 12 months after CERE-120 treatment appears to be persisting over longer time points," stated Jeffrey M. Ostrove, Ph.D., president and chief executive officer of Ceregene. "These positive clinical data offer further support for our recently enrolled multicenter Phase 2 trial for CERE-120 in the United States as well as our plans to initiate another Phase 2 trial that will begin in the third quarter of 2008 which will be conducted in several European countries in collaboration with Genzyme."
"I am encouraged that Parkinson's patients continue to respond well to CERE-120, over longer periods of time," stated Dr. Bartus. "Not only have we seen no treatment related serious adverse events at up to two years post dosing, but the apparent improvement seen at 12 months seems to continue as well. We, therefore, look forward to analyzing the results of our ongoing controlled Phase 2 trial of CERE-120 near the end of 2008 to determine whether they confirm the possibility that CERE-120 might significantly and persistently improve the symptoms of advanced Parkinson's disease patients."
This Phase 1 clinical trial was partially supported by a grant from The Michael J. Fox Foundation for Parkinson's Research. Based on the encouraging results of the Phase 1 study, the Foundation awarded another $1.9 million grant, which is providing partial funding for Ceregene's ongoing Phase 2 trial.
About Phase 2 Trial of CERE-120 Currently Underway
A double-blind, controlled Phase 2 clinical trial completed enrollment last month of 58 patients with advanced Parkinson's disease at nine medical centers in the United States, with two thirds of patients being enrolled in the active treatment group and one third in a control group. Patients received CERE-120 via stereotactic neurosurgery to deliver the drug into the putamen region of the brain and are being followed for 12 months for safety and efficacy. Clinical data from this trial are expected to be available in late 2008, and if the data are positive, a Phase 3 trial is expected to commence in 2009.
CERE-120 is composed of an adeno-associated virus (AAV) vector carrying the gene for neurturin (NTN), a naturally occurring protein known to repair damaged and dying dopamine-secreting neurons, keeping them alive and functioning normally. NTN 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 and are responsible for the major motor impairments. CERE-120 is delivered by stereotactic injection to the affected area of the brain, providing stable, long-lasting expression of NTN 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, a deal which was announced in June 2007.