Reaction to Withdrawal of Treatment

Contact: Allison Elliott

 

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“The need for new, and more effective, treatments is inarguable. Current treatments in the marketplace become increasingly less effective as the disease progresses, and do little to slow the increasing loss of dopamine cells in the brain, one of the root causes of the disease’s progression.”

-- John Slevin,
director,
Movement Disorders Clinic,
University of Kentucky

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LEXINGTON, Ky. (Feb. 11, 2005) -- University of Kentucky researchers learned today that pharmaceutical manufacturer Amgen Inc. has rejected a petition to continue compassionate use of a drug that may dramatically improve life for people living with Parkinson’s disease.

Ten Parkinson’s disease patients enrolled in a phase I clinical trial at UK experienced significant improvements in their quality-of-life while undergoing direct brain delivery of a natural brain protein known as glial cell line-derived neurotrophic factor (GDNF).

The results of the trial were dramatic. Patients who had difficulty completing simple tasks before receiving GDNF experienced substantial function improvements during therapy. UK was one of several international sites testing the drug, and t he results of the UK study appear in the February issue of the Journal of Neurosurgery. Despite the promising results of this clinical trial, Amgen halted distribution and testing of GDNF, citing safety and efficacy concerns.

“The need for new, and more effective, treatments is inarguable,” said principal investigator Dr. John Slevin, professor in the UK Department of Neurology and Department of Pharmacology and director of the Movement Disorders Clinic at UK. “Current treatments in the marketplace become increasingly less effective as the disease progresses, and do little to slow the increasing loss of dopamine cells in the brain, one of the root causes of the disease’s progression.”

“We are very disappointed by Amgen’s decision,” said Don Gash, the Alumni Chair in Anatomy and Neurobiology, professor in the Department of Anatomy and Neurobiology, and director of the M. Margrite Davis-Ralph E. Mills Magnetic Resonance Imaging and Spectroscopy Center. “The optimal scenario at this point would be for a third party organization to be allowed to take this project to the next stage by providing GDNF to patients as part of further clinical trials.”

UK researchers involved in the study give three reasons to continue the trials:

  • First, one of the safety concerns cited by Amgen in discontinuing the trials is the presence of focal cerebellar lesions after treatment with heavy doses of GDNF. However, the lesions were observed not in humans, but in animal models, said Gash. The animals involved in testing received much higher doses of the drug than is used in the treatment of humans.
  • Second, Amgen contends that benefits demonstrated during the trial may be the result of a placebo effect. Gash says that assumption is based upon a phase II study of GDNF in California, in which some of the patients receiving a placebo also experienced improvements. While some patients in the phase II trial showed a placebo response, there was not a significant overall placebo effect for the control group. Moreover, the phase I study conducted by UK did not have a placebo control group and was not blinded.
  • Amgen has reported the presence of antibodies to GDNF in some patients. However it is very common for antibodies to be generated in patients in response to protein drugs like GDNF. Gash says it is difficult to predict what the antibodies will do, but often they are harmless. Researchers at UK have not seen adverse responses in patients to the antibodies.

“We are increasing our testing of potential adverse effects of GDNF when large doses are used in animal models,” said Greg Gerhardt, professor in the Department of Anatomy and Neurobiology and Department of Neurology, director of the UK Morris K. Udall Parkinson’s Disease Research Center of Excellence, and director of the Center for Sensor Technology.

“These toxicity results should be taken very seriously. However, the varying results in the phase I and phase II trials are the best argument for why further testing is warranted, using methods similar to those employed in the successful phase I human trial conducted at UK,” Gash said.

“The patients and families who have staked their hopes, and indeed their lives, on the testing of new treatments for debilitating diseases such as Parkinson’s deserve nothing less.”


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