Alteon Inc. has temporarily suspended enrolment of patients in its ongoing clinical trials of alagebrium pending additional preclinical data and discussions with the Food and Drug Administration (FDA). The company is currently testing alagebrium in patients with systolic hypertension, heart failure and erectile dysfunction. Patients already enrolled in the clinical trials are continuing treatment. The company took this action voluntarily and has notified the FDA, the company announced here.
In December 2004, the company announced that findings of a two-year toxicity study indicated that male Sprague Dawley rats exposed to high doses of alagebrium over their natural lifetime developed dose-related increases in liver cell alterations and tumours, and that the liver tumour rate was slightly over the expected background rate in this gender and species of rat. The company also announced its intent to conduct a series of preclinical experiments to explore the mechanism by which the liver tumours developed and the relevance of such tumours to human exposure. These preclinical experiments are still ongoing, with results expected by mid-year, the release stated.
"This decision was made after we received initial data from one of our ongoing studies in rats, which provided insights and direction for further analysis," Judith S. Hedstrom, COO said adding, "The relevance of these rat findings to humans has not been established, and we do not believe that the recent data change the information previously provided to patients who are already in the alagebrium studies. Nevertheless, in the current environment, we have decided it is prudent to temporarily suspend enrolling new patients."
"We have decided to slow down our development programmes until the preclinical experiments are completed and the results evaluated over the next several months," said Kenneth I. Moch, president and CEO.
Earlier preclinical toxicity studies found no mutagenic or carcinogenic activity in either rats or mice. In addition, the company had previously completed four key genotoxicity studies to help determine potential toxicities of alagebrium in man, and these studies did not indicate any potential carcinogenic risk. Alteon has reviewed all of the cumulative human safety profile and previous preclinical experience of alagebrium; these data have not demonstrated an association with the lifetime carcinogenicity study in rats. All patients in the clinical trials of alagebrium had been previously informed of the initial findings in rats, and the incremental data do not alter the information that had already been provided to them, the release concluded.