5 replies to this topic

[caliban]

Alteon Inc.

The development-stage pharmaceutical company's drugs are designed to inhibit or block damage caused by advanced glycosylation endproducts (AGE).
Lead drug candidate alagebrium chloride, also known as ALT-711, breaks protein crosslinks and may inhibit cardiovascular disease; the drug may also have other indications.
Another candidate, Pimagedine, may treat kidney diseases and impaired kidney function;
Also in its pipeline are glucose-lowering agents to treat type 2 diabetes.

http://www.alteon.com/

[caliban]

So, at least Osiris is interrested in this (and probably knows it already)

A couple of days ago, Alteon slumped quite a bit after announcing that they discontinue the SPECTRA trial, a Phase 2b clinical trial for alagebrium (thats what they call ALT-711 now), against uncontrolled systolic hypertension.
While the drug has been observed to be safe (so they say, this was under dispute earlier) the efficacy review was unfavorable.

One could have speculated on this outcome after a press release in May where they said they would review the trial, but there it looked like safety, not efficacy would be the issue.

Now there is some nice data on the efficacy of ALT-711 (can't get used to the other name) so its not all doom and gloom. Far as I know, they still have phase 2 trials on heart failure and erectile dysfunction running.
They say they have other AGE breakers in the portfolio, but I don't know much about that. Could be just derivatives.
They also used to reserach AGE (Pimagedine) but I guess they figured out that there was no money in them.

So overall, I'd like someone so say something encouraging to Osiris now:

[Mark Hamalainen]

Furtunately I don't have very much money invested.

[John Schloendorn]

Heh now if that wasn't encouraging [lol] [thumb]

[Michael]

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]

[caliban]

http://en.wikipedia....wiki/Alagebrium

Alagebrium (formerly known as ALT-711) is a failed[why?] drug candidate developed by Alteon Corporation. It was the first drug to be clinically tested for the purpose of breaking the crosslinks caused by advanced glycation endproducts (A.G.E.s), thereby reversing one of the main mechanisms of aging.[1] Through this effect Alagebrium is designed to reverse the stiffening of blood vessel walls that contributes to hypertension and cardiovascular disease, as well as many other forms of degradation associated with protein crosslinking.[2][3][4] Alagebrium has proven effective in reducing systolic blood pressure[5] and providing therapeutic benefit for patients with diastolic heart failure.[6]
Contents [hide]
1 Mechanism
2 History
3 See also
4 References
[edit]Mechanism


This article's section called "Mechanism" does not cite any references or sources.
Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (April 2010)
A.G.E.s are permanent carbohydrate structures that form when carbohydrates bind to proteins, lipids and DNA. Many proteins, including structural proteins such as collagen and elastin, play an integral role in the architecture of tissues and organs and maintenance of cardiovascular elasticity and vascular wall integrity. Diabetic individuals form excessive amounts of A.G.E.s earlier in life than non-diabetic individuals. This process can impair the normal function of organs that depend on flexibility for normal function, such as blood vessels and cardiac muscle. The formation of A.G.E. crosslinks leads to increased stiffness and loss of function of tissues and organs, and abnormal protein accumulation, which together cause many of the complications of aging and diabetes. A.G.E.s are also known to induce oxidative stress, in which reactive molecules provoke the underlying component of inflammation.
Pharmacologic intervention with alagebrium directly targets the biochemical pathway leading to the stiffness of the cardiovascular system. Removal of the A.G.E.s by cleavage of the abnormal crosslinking bonds has been associated with diminished inflammatory and sclerotic signaling pathways. These pathways are responsible for the deposition of abnormal amounts of matrix proteins that physically stiffen tissues. The presence of A.G.E. crosslinks also renders tissues and organs less susceptible to normal turnover thus enhancing the presence of these abnormal bonds on various molecules. Importantly, alagebrium does not disrupt the natural carbohydrate modification to proteins, intra-molecular crosslinking or peptide bonds that are responsible for maintaining the normal integrity of the collagen chain. Thus, normal structure and function is preserved while abnormal crosslinking is reduced.
Although alagebrium may break some important A.G.E. crosslinks, there is no evidence that it is effective against the most prevalent crosslink: glucosepane.[7]

[edit]History

The neutrality of this article is disputed. Please see the discussion on the talk page. Please do not remove this message until the dispute is resolved. (April 2010)
The chemical compound had been discovered many years ago, and had traveled a circuitous route through academia, research firms, and finally, Alteon. There are two prominent attributes to Alagebrium (as Alteon renamed it). The first is that it is not a difficult compound to synthesize. An active black market rose very quickly after the early Phase I and II tests came in. Independent, lab-tested, certified for purity product was available for a short time on the grey market at about $3 per gram.
Although Alagebrium has shown very promising Phase I and II clinical trials, active research stopped because Alteon had run out of operating cash.[8] Alteon, having a huge amount of convertible preferred stock hanging over its head (held by Genentech), had increasing difficulty raising subsequent levels of venture capital until finally, it was unavailable at any price. On 25 July 2007 Alteon was bought by a three-man operation[who?] developing another medication. The company changed its name to Synvista Therapeutics, Inc.