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Amgen Responds

Amgen: No clinical improvement seen, serious safety issues (June 28, 2004)

Amgen scientists analyzed study data after six months of treatment and saw no significant difference in symptom improvement (as defined by the Unified Parkinson's Disease Rating Scale) between trial participants who received GDNF, and those who were given a placebo.
Striking results in earlier trials were probably the result of a placebo effect.
The study was well conducted, showing biological activity, but without a corresponding clinical response. PET brain imaging scans showed improvement in dopamine production and use at the site where GDNF was being infused. (1)
Amgen secured FDA approval to halt all human testing of GDNF after discovering two serious safety issues “never seen before in any previous studies.”
- Four patients developed GDNF antibodies, “but the significance of this is unknown and the patients remain asymptomatic.” (2)
- Two of 70 monkeys from preclinical studies developed small lesions in the cerebellum region of the brain that governs movement and balance.
Financial considerations had nothing to do with the decision to halt the trial.

The trial’s failure was "the single most disappointing" one in his 12 years at Amgen, said CEO and Chairman Kevin Sharer. Hundreds of millions of dollars and 10+ years were spent developing GDNF, once considered one of the most promising approaches to a disease that affects 500,000 to 1.5 million Americans, Sharer said. (3)

Citing no evidence of benefit, and serious safety concerns, Amgen said :

It was no longer ethical to administer GDNF to patients.
Licensing GDNF to another company or a university willing to continue trials would leave Amgen liable if safety issues arose.
GDNF does not meet FDA qualifications for “compassionate use” because it is no longer under development and has known safety problems.

“We were surprised when we unblinded the study and saw there was no benefit,” said Dr. Roger Perlmutter, Executive Vice President for Research and Development. “There was a large placebo effect,” meaning patients on and off the medicine showed signs of improvement. (4)

“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,” said Beth Seidenberg, M.D., Chief Medical Officer and Senior Vice President, Amgen. (5)

(1) Gardner, Amanda. “Trial Halted for Promising Parkinson’s Drug.” WCNC.com website, October 5, 2004. Retrieved online.

(2) E-MOVE. “Antibodies to GDNF Force Halt to All Clinical Trials.” E-MOVE reports from the 129th Annual Meeting of the American Neurological Association, held in Toronto October 2-6, 2004.

(3) Pollack, Andrew. “Many See Hope in Parkinson's Drug Pulled From Testing.” New York Times, November 26, 2004.

(4) Talan, Jamie. “Drug trial – and error?” Newsday, November 22, 2004.

(5) “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” Amgen press release, June 28, 2004.

Amgen's press releases

2/11/2005

Following Complete Review of Phase 2 Trial Data Amgen Confirms Decision to Halt GDNF Study; Comprehensive Review of Scientific Findings, Patient Safety, Drove Decision

Read Amgen's Press Release

6/28/2004

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

Read Amgen's Press Release

3/23/2004

Amgen's First Research and Development Day Highlighted 24 of the Approximately 40 Programs in its Pipeline

Company Reported 14 Programs in Phase 2 or Phase 3 Clinical Development

Read Amgen's Press Release

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