View Full Version : CERE-120 Ceregene...Trial Information

04-05-2007, 08:35 AM
Study of CERE-120 in People with Parkinson’s Disease
Official Study Title: Randomized, Double-Blind, Sham Surgery-Controlled Study of CERE-120 (Adeno-Associated Virus Serotype 2 [AAV2]-Neurturin [NTN]) to Assess the Efficacy and Safety of Bilateral Intraputaminal (IPu) Delivery in Subjects with Idiopathic Parkinson’s Disease

Double-Blind, Multicenter, Sham Surgery Controlled Study of CERE-120 For Efficacy and Safety in Subjects With Idiopathic Parkinson's Disease
This study is currently recruiting patients.
Verified by Ceregene March 2007

Recombinate DNA Advisory Committee
Meeting Minutes
September 2006

PowerPoint Presentation
CERE-120 (AAV-Neurturin) for Parkinson’s Disease
NIH OBA Protocol # 0501-689
A Phase I, Open-Label Study of CERE-120 (Adeno-Associated Virus Serotype 2 [AAV2]-Neurturin [NTN] to Assess the Safety and Tolerability of Intrastriatal Delivery to Subjects with Idiopathic Parkinson's Disease

04-07-2007, 04:15 PM

Thanks for posting this - neurturin is a neurotrophic factor in the same family as GDNF. Since Amgen is withholding its synthetic GDNF from us, this treatment may be the next best thing for PWP.

Last week I talked to one of the scientists at the MJFOX Foundation at length about this trial. The scientist said that if the treatment is found to work in the Phase II trial, those patients who got the sham surgery could get the real surgery after that trial's end. The participants would not have to wait until after the Phase III trial - they could get the treatment after the Phase II trial is finished -- assuming the results show that neurturin works.

And thanks to all PWP who are considering joining this trial. Without trial participants, we will never have better treatments - or a cure.

04-07-2007, 07:40 PM
Jean, I have put my name into the hat for the Ceregene trial. I hope to hear from them this coming week.

I understand that Duodopa Phase II trial should begin this summer sometime. Another option for every one to consider.
Solvay Pharmaceutisals...Duodopa
http://www.duodopa.com/faqs/faqsaboutduodopa/0,,39990-2-0,00.htm - Q&A

November 28, 2005: Solvay Pharmaceuticals completes market authorization in 28 European countries for Duodopa®
Solvay Pharmaceuticals has obtained market authorization for DUODOPA®, the product for treating advanced Parkinson’s disease in 28 European countries.

e-Move 2004: http://www.mdvu.org/emove/article.asp?ID=722

04-08-2007, 04:55 AM
if Duodopa is approved in Europe then why is it back at phase 2 in the US.

Its no wonder drugs take so long to get to market.

Have I misunderstood the situation ?


04-08-2007, 08:13 AM
Actually it is a Phase III that is coming over to the US. A lady from Solvay was at the PAN forum and I spoke with her. They were supposed to start recruiting in January, but have pushed it back to summer.

She said she didn't understand the FDA...lol

After completing a very short registration to receive a user name and password, you can see the info about all the PD trials with history and pharmaceutical companies here.



04-08-2007, 11:11 AM
Actually it is a Phase III that is coming over to the US. A lady from Solvay was at the PAN forum and I spoke with her. They were supposed to start recruiting in January, but have pushed it back to summer.

She said she didn't understand the FDA...lol

After completing a very short registration to receive a user name and password, you can see the info about all the PD trials with history and pharmaceutical companies here.



Hi Paula;
IS their any word on complication rates??
Blockages, infections, etc.??

I remember seeing that video of the Scandinavian college professor at PAN 2002 or there abouts. It was very impressive, especially how the peak dose dyskinesias where controlled.


04-08-2007, 11:16 AM
2007 will bring us some very hopeful treatments in clinical trials:

-- ceregene120 - phase II, 2007
-- duodopa - phase III, 2007
-- neurologix - phase II, latter half of 2007

04-08-2007, 01:57 PM
Spheramine (phase IIb) due late 2007 / early 2008.


04-08-2007, 03:06 PM
Spheramine as well! :eek:
thanks, Neil

04-16-2007, 11:57 AM
Ceregene Presents Long Term Follow-Up Data From Phase 1 Trial of CERE-120 Demonstrating Improved Motor Function in Parkinson's Patients


Encouraging Results Prompted Phase 2 Study Now Underway at Nine Centers

SAN DIEGO, Calif., April 16 /PRNewswire/ -- Ceregene, Inc., a
biopharmaceutical company, today presented long term follow-up data from a
Phase 1 clinical trial of CERE-120, a gene therapy product in development
for the treatment of Parkinson's disease, demonstrating a 36 percent
(p<0.001) reduction in Parkinson's symptoms at 12 months after
administration, 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 was also shown to be
well tolerated in this study. The 12-month results were presented today by
Philip Starr, M.D., Ph.D., associate professor of neurosurgery at the
University of California, San Francisco at the American Association of
Neurological Surgeons (AANS) annual meeting in Washington D.C. These data
were also highlighted by the AANS in a specific CERE-120 press release
issued by the Association.

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.
All 12 patients enrolled in the study underwent stereotactic neurosurgery
to deliver CERE-120 into their putamen -- a region of the brain affected by
the degeneration of neurons in Parkinson's disease.

CERE-120 was delivered at two different doses, and patients receiving
the low dose demonstrated approximately 36 percent improvement in UPDRS
motor "off" scores by nine months and patients receiving the four-fold
higher dose showed a similar effect three months sooner. This statistically
significant, 36 percent improvement was maintained in both groups at the
12-month mark, the final follow-up time point in the study. Patients also
demonstrated a 50 percent 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.

This Phase 1 clinical trial was partially supported by a grant from The
Michael J. Fox Foundation for Parkinson's Research. Based on the results of
the Phase 1 study, the Foundation has provided a $1.9 million grant, which
will provide partial funding for Ceregene's ongoing Phase 2 trial.

"We are pleased with the results of this early study which suggests
that the majority of patients treated with CERE-120 may have exhibited
significant and stable improvement for a full year after receiving a single
administration of CERE-120," stated Jeffrey M. Ostrove, Ph.D., president
and chief executive officer of Ceregene. "Each of our products, much like
CERE-120, is aimed at unmet neurodegenerative diseases including
Parkinson's disease, Alzheimer's disease and Amyotrophic Lateral Sclerosis
(AML or Lou Gehrig's disease) with the goal of not only improving the
symptoms but also preventing progression of the disease."

"Through stereotactic surgery, we are able to administer CERE-120 in a
highly targeted fashion to one area of the brain that Parkinson's disease
affects, and we were able to do this safely," stated Dr. Starr.

"Given the encouraging data from the Phase 1 trial of CERE-120 in
Parkinson's disease, we are conducting a follow-on Phase 2 clinical trial
that is currently enrolling patients at nine clinical trial sites in the
United States," said Raymond T. Bartus, Ph.D., Ceregene's senior vice
president of clinical and preclinical R&D and chief operating officer. "The
data from the Phase 1 trial are reflective of the impressive results we
gathered from preclinical studies, which demonstrated the ability of
CERE-120 to stimulate the survival and improve the function of key neuronal
cells affected by Parkinson's disease, as well as an excellent safety
profile over a wide range of CERE-120 dose levels."

About Phase 2 Trial of CERE-120 Currently Underway

A double-blind, controlled Phase 2 clinical trial is now enrolling 51
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 the control group. Patients are receiving
CERE-120 via stereotactic neurosurgery to deliver the drug into the putamen
region of the brain. Patients will be followed for 12 months for safety and
efficacy. Contacts at the medical centers involved in this study can be
found through a link on the Ceregene web site: http://www.ceregene.com.

About CERE-120

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. Ceregene owns
exclusive technology and product rights to CERE-120.

About Ceregene

Ceregene, Inc. is a San Diego-based biotechnology company focused on
the development of gene therapies for neurodegenerative disorders. Ceregene
is in the clinic with CERE-110, an AAV2 based vector expressing nerve
growth factor that is being tested as a treatment for Alzheimer's disease,
and with CERE-120 for Parkinson's disease. CERE-130 is in late preclinical
development for ALS. Ceregene was launched in January 2001 and is a former
subsidiary of Cell Genesys, Inc. (Nasdaq: CEGE), which is headquartered in
South San Francisco, CA. Ceregene's investors include Alta Partners, MPM
Capital, Investor Growth Capital and Cell Genesys, as well as Hamilton
BioVentures and, California Technology Partners.

About The Michael J. Fox Foundation

Founded in 2000, The Michael J. Fox Foundation for Parkinson's Research
is dedicated to ensuring the development of a cure for Parkinson's disease
within this decade through an aggressively funded research agenda. The
Foundation has funded more than $90 million in research to date, either
directly or through partnerships.

04-16-2007, 12:04 PM
Novel Gene Therapy Treatment for Parkinson’s Disease Shows Promise

Released: Fri 06-Apr-2007, 11:00 ET
Source: American Association of Neurological Surgeons (AANS)

Description: It is estimated that 60,000 new cases of Parkinson’s disease (PD) are diagnosed each year, adding to the estimated one to 1.5 million Americans who currently have the disease. Existing therapies for PD treat only the symptoms, and are effective for a limited period of time. Results of this Phase I Trial utilizing AAV-Neurturin are encouraging for the many PD patients who do not respond to existing therapies.

Newswise — It is estimated that 60,000 new cases of Parkinson’s disease (PD) are diagnosed each year, adding to the estimated one to 1.5 million Americans who currently have the disease. The latest epidemiology studies indicate that worldwide numbers will increase from an estimated 4.1 million in 2005 to 8.7 million people with PD by 2030. There were nearly 18,000 PD-related deaths in the United States in 2004. While the condition usually develops after the age of 55, the disease may affect people in their 30s and 40s.

Early in the disease, there is a loss of brain cells that produce the chemical dopamine. Normally, dopamine operates in a delicate balance with other neurotransmitters to help coordinate the millions of nerve and muscle cells involved in movement. Without enough dopamine, this balance is disrupted, resulting in tremor (trembling in the hands, arms, legs and jaw); rigidity (stiffness of the limbs); slowness of movement; and impaired balance and coordination – the hallmark symptoms of PD.

In the last 10 years, protein substances called “growth factors” have been discovered that can slow or halt the death of dopamine-producing cells. One such factor, known as “GDNF” (Glia-Derived Neurotrophic Factor), has been used in clinical trials for PD. The results have been inconsistent, possibly related to the method of delivering the protein to the brain.

Researchers at the University of California at San Francisco, and Rush-Presbyterian Medical Center in Chicago, in conjunction with Ceregene, Inc. of San Diego, Calif., recently undertook a Phase I trial using a novel strategy called “gene transfer” to deliver a growth factor to the brains of 12 patients with PD. All patients entered in the trial were judged to have inadequate control of their disease with standard levadopa therapy and would have otherwise been potential candidates for treatment interventions such as deep brain stimulation (DBS).

The results of this study, Intrastriatal Gene Transfer with AAV-Neurturin for Parkinson’s Disease: Results of a Phase I Trial, will be presented by Philip A. Starr, MD, PhD, 11:45 am to 12:00 p.m. on Monday, April 16, 2007, during the 75th Annual Meeting of the American Association of Neurological Surgeons in Washington, D.C. Co-authors are Leo Verhagen, MD, Paul S. Larson, MD, Roy Bakay, MD, Robin Taylor, RN, Deborah Cahn-Weiner, PhD, Raymond Bartus, MD, Jill L. Ostrem, MD, and William J. Marks Jr., MD.

The growth factor gene was delivered as part of a modified virus, or “viral vector”, called adeno-associated virus (AAV). This viral vector helps enable the gene to be delivered into the correct brain cells, but has been modified so that it cannot reproduce or damage brain cells. The growth factor gene neurturin was utilized, which is a protein closely related to GDNF. Neurturin has been shown in laboratory studies to help prolong survival of dopamine-making cells. AAV-neurturin was delivered directly to the brain via stereotactic injection through multiple (16) needle injections into the striatum, the part of the brain most deficient in dopamine. This was performed through small openings in the skull.

The patients were studied using standard rating scales of movement in PD, the Unified Parkinson’s Disease Rating Scale (UPDRS) prior to surgery and on a continual basis post surgery, at baseline, 1, 3, 6, 9 and 12 months, on and off medication. Two different doses of the viral vector were tested, the lower dose in the first six patients, and the higher dose in the remaining six patients. The following outcomes were noted:

There were no major adverse effects from this treatment at the low or high doses.
In nine of the 12 patients for which one-year outcome data was available, the improvement in the UPDRS was 38 percent.

“Patients with PD urgently need therapeutic approaches that not only improve their symptoms and daily functions, but positively modify the underlying components of the disease, stated Dr. Starr.

“Existing therapies for PD treat only the symptoms, and are effective for a limited period of time, so any trial that is safe and results in promising efficacy data is worth pursuing. The safety data and preliminary efficacy data that resulted from this Phase 1 study are encouraging, and clearly warrant the need for a larger, Phase II study,” concluded Dr. Starr.