Amgen Inc.'s therapy for Parkinson's disease failed to meet its primary endpoint in a Phase II study.

The company's glial cell line-derived neurotrophic factor, also called GDNF, did not show an improvement in symptoms as defined by the Unified Parkinson's Disease Rating Scale (UPDRS), despite positive results seen in an open-label study conducted in the UK.

"We are very, very committed to figuring out what we can do next," said Andrea Rothschild, an Amgen spokeswoman. "There have been very few breakthroughs in this disease area. There have been a lot of disappointments. We think GDNF has been one of the more interesting candidates in the field."

While it's too soon to say what the fate of the drug might be, Thousand Oaks, Calif.-based Amgen will conduct a deeper analysis of the data to determine if GDNF has a better chance of succeeding at a higher dose or with a longer trial duration. The company plans to provide more detailed data at the annual meeting of the American Neurological Association in October.

The Phase II study divided 34 patients into two groups, those receiving a 15-mg daily dose of GDNF and those receiving placebo. Patients in the drug group received direct, continuous infusion of GDNF into the putamen, a region of the brain known to be affected by Parkinson's disease. Initial analysis of preliminary data showed no clinical improvement compared to placebo following six months of treatment, but it did show evidence of alteration in brain function and was found to be safe and well tolerated. All patients in the study now are receiving GDNF in an open-label extension.

The UK open-label study has followed five patients over the last three years that have demonstrated the drug to be more efficacious, showing an improvement in symptoms as defined by the UPDRS. The recent Phase II study was designed based on one-year data of the open-label trial.

"The patients have all done well in terms of tolerating the drug," Rothschild told BioWorld Today. "We know that that's the same thing that occurred in the open-label study. We know that it's going where it needs to go in the brain, and that's a good thing. The difference is there was no clinical improvement in six months."

Researchers have found that the GDNF gene keeps alive or regenerates dopaminergic neurons that die in patients with Parkinson's disease. Amgen's drug attempts to attack the pathological process of the disease, while current therapies help control the symptoms. Those therapies on the market help Parkinson's patients overcome rigidity and regain movement, but they also cause side effects, such as dyskinesia, and they require more frequent dosing to remain effective. While deep-brain stimulation seems to work well, it only provides relief from symptoms, Rothschild said.

"I think the big potential benefit that was seen with GDNF was its ability to actually modify the disease progression, which is not present in any therapy for Parkinson's," she said.

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 tissues. The company gained the program through its 1994 acquisition of Boulder, Colo.-based Synergen Inc. for $258 million. (See BioWorld Today, Nov. 21, 1994.)

Worldwide, Parkinson's disease afflicts about 4 million people, about a quarter of whom live in the U.S.

"It's a tough day for the patients, and that is important," Rothschild said. "They are really looking for something that changes the course of the disease, so from that perspective, it's a bit disappointing for Amgen to be delivering this news."

Aside from GDNF, Amgen has 40 programs in development, 14 of which are in Phase II or Phase III trials. It reported total product sales of $2.2 billion worldwide in the first quarter. As of March 31, the company had $4.5 billion in cash and marketable securities.

Last week, Amgen submitted its biologics license application for palifermin to treat oral mucositis. (See BioWorld Today, June 25, 2004.)

The company's stock (NASDAQ:AMGN) dropped 57 cents on Monday, to close at $53.56.

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