All:
The FDA is also maintaining a moratorium on a clinical trial of Alagebrium for erectile dysfunction based on safety concerns (possible hepatotoxicity in rats):
FDA Maintains Clinical Hold on Alteon's ED Study of Alagebrium
PARSIPPANY, N.J., Sept. 30 /PRNewswire-FirstCall/ -- Alteon Inc. (Amex: ALT) announced today that it has been notified by the U.S. Food & Drug Administration's (FDA) Reproductive and Urologic Drug Products Division that it is maintaining the clinical hold previously placed on the Company's Phase 2a study of alagebrium in diabetic patients with erectile dysfunction. In June, the Company announced that it had submitted preclinical toxicity data on alagebrium to two divisions of the FDA's Center for Drug Evaluation and Research (CDER), specifically the Division of Cardio-Renal Drug Products and the Division of Reproductive and Urologic Drug Products. The preclinical toxicity data were submitted in support of the Company's view that liver alterations previously observed in rats were related to the male rat metabolism and not to genotoxic pathways. Preliminary data on liver alterations in rats had caused the Company to voluntarily suspend enrolling new patients into its clinical trials.
It should be noted, since it isn't well-known, that aminoguanidine development was suspended due to the double whammy of lack of efficacy
and side effects:
Phase III clinical trials of aminoguanidine were completed in 1998. These included a randomised, double-blind ACTION I trial where the ability of aminoguanidine to prevent progression of renal nephropathy was investigated in 690 type 1 diabetic patients. Patients were placed on either placebo, high (600 mg per day) or low (300 mg per day) dose of aminoguanidine. The primary endpoint was the doubling of the serum creatinine with deteriorating renal function. Aminoguanidine therapy reduced progression of diabetic retinopathy, lowered LDL and triglyceride levels and reduced urinary albumin excretion significantly [88,89]. However, the primary endpoint could not be met because although aminoguanidine treatment reduced the risk of doubling serum creatinine, this was not statistically significant [77]. A similar ACTION II trial was conducted using 599 type 2 diabetic patients but was discontinued due to safety concerns and lack of efficacy of aminoguanidine. Aminoguanidine is reported to have side effects in patients, which include flu-like symptoms, gastrointestinal disturbances and anaemia [90]. Despite the earlier promising results with aminoguanidine, it is unlikely to be used for therapeutic purposes. However, studies on antiglycation compounds like aminoguanidine have provided evidence for the involvement of AGEs in the pathogenesis of diabetic complications. (1)
Alteon
still haven't clearly said this on their website, tho' they have finally indicated that "Alteon is not in active development with pimagedine at this time."
-Michael
1: Ahmed N.
Advanced glycation endproducts--role in pathology of diabetic complications.
Diabetes Res Clin Pract. 2005 Jan;67(1):3-21. Review.
PMID: 15620429 [PubMed - indexed for MEDLINE]