Ceregene Presents Additional Clinical Data from Phase 2 Trial of CERE-120 for Parkinson's Disease

http://news.prnewswire.com/ViewConte...5032921&EDATE=

-- Longer term follow-up indicates modest efficacy in primary and related endpoints --

SAN DIEGO, May 27 /PRNewswire/ -- Ceregene, Inc. today reported additional clinical data from a double-blind, controlled Phase 2 trial of CERE-120 in 58 patients with advanced Parkinson's disease. CERE-120 uses AAV-based gene therapy to deliver the neurotrophic factor, neurturin, to Parkinson's disease patients in order to restore the function and protect degenerating nigrostriatal neurons. The company previously announced that the Phase 2 trial did not meet its primary endpoint of improvement in the Unified Parkinson's Disease Rating Scale (UPDRS) motor off score at 12 months of follow-up, although several secondary endpoints suggested a modest clinical benefit.

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 San Diego, CA by Raymond T. Bartus, Ph.D., Ceregene's executive vice president and chief scientific officer.

"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 Jeffrey M. Ostrove, Ph.D., president and chief executive officer of Ceregene. "The information gained from this initial controlled Phase 2 trial in advanced Parkinson's disease patients has been invaluable, and we can now incorporate these insights in a follow-on clinical trial that we are planning to initiate later this year. Our goal remains to significantly improve the symptoms of Parkinson's patients and also to provide the opportunity to delay further disease progression."

you can say this is an example of clinical trials working, on the other hand if the two patients hadn't been unlucky enough to have died I wonder how much of this data would have been obtained.

Still perhaps there was no other way and this data appears to have been invaluable.

Further trials late in the year, with Prosavin, Neurologix and now Ceregene still in the game perhaps the gene therapy story has a few more surprises to come.
I must admit I had lost faith upto now.

Thanks for this, it has brightened my day.

Neil.

I am told through the Cere-120 patient/participant-grapevine that the shammed group is being asked back into the trial protocol for ongoing evaluation. To my knowledge, they were released after the trial ended and the December 2008 results were released. Only those of us who received the actual treatment were to be followed for life.

Why are they really being called back into eval, especially is they are unblinded to Ceregene?
Were they unblinded upon release?
Were they actually released back in 2008 or early 2009, or at their individual 18-month post surgery date? The last surgical patient would have hit 18-months in April 2009.

I am told through the grapevine that they are being "recalled" at the two-year mark the treated participants (me included) are showing improvement on the trial measurement...the UPDRS.

My two-year eval is in late June. At two-years we have another MRI.

I have emailed my Trial Coordinator to confirm comments I have heard, but I have not yet heard back from her.

I did note that the above press release also says, "the 30 subjects who continued to be evaluated under double-blind conditions"...I was under the understanding that we were ALL unblinded at the end of the trial period of 12-months. We do continue to have a Blinded Rater, maybe this should have been my indicator...hummm. Or maybe the fact that my hotel reservations are not in my name, but in Ceregene's name should have been my hint.