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PDF Responds to Amgen Announcement on GDNF Trial
- Jul 01 2004
Earlier today, the Amgen company announced that its widely-watched clinical trial of the efficacy of a neuronal growth factor in treating advanced Parkinson’s has failed to demonstrate any clinical improvement after six months of use.
The finding has surprised many because it seems to be at odds with an earlier, smaller “open-label” study in the U.K that had suggested strong therapeutic potential for the compound, a protein known as glial cell line-derived neurotrophic factor (GDNF).
In a response to the Amgen announcement, Dr. Stanley Fahn, Scientific Director of the Parkinson’s Disease Foundation acknowledged that the news will be disappointing to members of the Parkinson’s community and to scientists but noted that “A negative trial result does not necessarily mean that the compound in question is of no therapeutic value – especially when that compound has demonstrated promise in animal studies and earlier, smaller, human trials.” He said that “a variation in the study design (e.g. different duration, different dosage, different patient selection criteria, a change in method of drug delivery) may yield different results, and should be explored before any particular approach is abandoned.”
He also said that disappointments of this kind in clinical trials “show how important it is that we remain open to all promising approaches to therapeutic intervention, rather than focusing on a single one. As for GDNF and other growth factors like it, the experience shows that we need to spend more time exploring the basic neurobiology of these compounds – how exactly they work in the environment of the human brain and what can be done to prepare this environment to take the best advantage of them.”
He concluded: “We hope that Amgen will continue to explore the potential of this compound.”
In a conversation with PDF staff, Amgen officials have said that specific data from the trial will be released once analysis is complete and that a full report will be submitted for presentation at the October, 2004 meeting of the American Neurological Association. In the meantime, the company is continuing to analyze the data, including comparing the experience of subgroups within the study population of 34 patients, and talking with investigators.
The full text of the Amgen announcement reads as follows:
Amgen's Phase 2 Study of GDNF for Advanced Parkinson's Disease Fails to Meet Primary Endpoint; Six Months of Treatment Showed Biological Effect But No Clinical Improvement
THOUSAND OAKS, Calif.--June 28, 2004--Amgen (Nasdaq:AMGN), the world's largest biotechnology company, today announced that the Phase 2 study of its novel glial cell line-derived neurotrophic factor, or GDNF, for the treatment of advanced Parkinson's disease did not meet the primary study endpoint upon completion of six months of the double-blind treatment phase of the study. In the study, GDNF was safe and well-tolerated.
The Phase 2 randomized, double-blind placebo-controlled study involved 34 patients with advanced Parkinson's disease who received direct, continuous infusion of GDNF into the putamen, a region of the brain known to be affected by Parkinson's disease. The primary endpoint of the study was improvement of symptoms as defined by the Unified Parkinson's Disease Rating Scale, a measurement tool that assesses the status of patients suffering from Parkinson's disease. Initial analysis of the preliminary data showed no clinical improvement compared to placebo following six months of treatment, despite evidence of alteration in brain function. All patients in the trial are receiving GDNF in an open label extension study.
"We are currently analyzing the data to understand why this study differs from the long-term improvement of the patients, who have been treated with GDNF for close to three years in an ongoing open-label study being conducted in the United Kingdom," said Beth Seidenberg, M.D., chief medical officer and senior vice president, Amgen. "We are committed to understanding if a different approach, including evaluating a higher dose, may yield an outcome that is consistent with the open label study."
Further details about the trial will be available when all data analyses are complete. Data from the study are being submitted for presentation at the annual meeting of the American Neurological Association in October.
Amgen's recombinant GDNF protein is a duplicate of a naturally occurring GDNF found in the central nervous system that promotes the growth, regeneration and protection of specific nervous tissue.
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Source Date: Jul 01 2004