BioWorld International Correspondent

DUBLIN, Ireland Elan Corp. plc is continuing development of an additional four or five candidate therapeutic vaccines for Alzheimer’s disease, following the failure of the program’s lead compound, AN-1792, in Phase IIa trials, the company’s chief scientific and medical officer, Ivan Lieberburg, told BioWorld International.

Dublin-based Elan and its partner, the Wyeth-Ayerst Laboratories pharmaceutical division of American Home Products Corp., of Madison, N.J., discontinued the AN-1792 trial Friday, following the development of symptoms of central nervous system (CNS) inflammation in 11 patients at several trial centers.

They had reported in late January a similar observation in four patients in France. The company had received no further reports of adverse events by late Monday. “It is conceivable we could see some more,” Lieberburg said.

AN-1792 comprises a 42-amino-acid form of the beta-amyloid peptide that is implicated in the deposition of plaque in the brain of Alzheimer’s patients, combined with the adjuvant QS21.

“This was the first product out the door. Unfortunately, we hit this rough patch,” Lieberburg said. In previous Phase I studies, more than 100 patients received the drug without any apparent signs of CNS inflammation. The present study involved around 360 subjects with mild to moderate Alzheimer’s.

It is not yet clear how the side effects arose at such a relatively low frequency. One possible explanation, Lieberburg said, is that subjects with particular tissue types do not tolerate AN-1792. “We’re still typing the patients so we don’t know if that theory will hold water,” he said. Even if this were to be the case, the compound is unlikely to undergo further development. “The data would have to be truly compelling,” he said.

Instead, the company is turning its attention to other vaccine candidates in the same program, although Lieberburg was unable to comment on the timing of their entry into clinical trials. “Suffice it to say they’re in late stage preclinical development right now. They’re in the final stages of testing,” he said.

These compounds are, like AN-1792, variations of the beta-amyloid peptide. “Each one is designed in a separate way,” he said. The therapeutic rationale is to promote clearance and degradation of beta-amyloid plaques by stimulating the production of antibodies that recognize them.

Elan has an additional Alzheimer’s alliance with Pharmacia Corp., of Peapack, N.J., which takes an alternative approach. The companies are seeking inhibitors of beta-secretase, an enzyme associated with a cleavage event that leads to the development of amyloid plaques. “That’s going very well. We have very potent molecules,” Lieberburg said. “Once again, we hope to get those into the clinic as soon as possible.”