Alteon Initiates Phase 2 Trial of Alagebrium in Erectile Dysfunction
18 Januar 2005 - 5:10PM
PR Newswire (US)
Alteon Initiates Phase 2 Trial of Alagebrium in Erectile
Dysfunction - 'EMERALD' Trial to Test the Efficacy of Alagebrium in
Diabetic Men Who Achieve Limited Benefit from Current Therapies -
PARSIPPANY, N.J., Jan. 18 /PRNewswire-FirstCall/ -- Alteon Inc.
(AMEX: ALT) announced today that it has initiated a Phase 2 trial
of its novel A.G.E. Crosslink Breaker compound alagebrium chloride
(formerly known as ALT-711) in erectile dysfunction (ED). EMERALD
(Evaluation of Alagebrium in Erectile Dysfunction in Diabetic Males
on PDE5 Inhibitors) will assess the ability of alagebrium to
restore erectile function in diabetic patients with moderate to
severe ED who achieve limited benefit from current treatment with
phosphodiesterase type 5 (PDE5) inhibitors, the first class of
orally active compounds approved for the treatment of ED.
Alagebrium has demonstrated an ability to reverse ED in a
preclinical model of ED in diabetic rats -- through what appears to
be a unique mechanism of action -- and thus may offer significant
potential as an adjunctive treatment for diabetic ED. About EMERALD
EMERALD is a randomized, double-blind, placebo-controlled, Phase 2
pilot study being conducted under the direction of Wayne J.G.
Hellstrom, M.D., F.A.C.S., Professor of Urology at Tulane
University School of Medicine and an author of many of the seminal
studies in ED.(1) Approximately 40 male diabetic patients age 18 to
70 will be enrolled and randomized to receive oral doses of either
alagebrium (200 mg once daily) or placebo tablets for a 16- week
period in conjunction with their PDE5 inhibitor therapy. The
primary endpoint of the trial will be based on the International
Index of Erectile Function (IIEF) questionnaire. Secondary
endpoints of efficacy will be self- reported improvement in
erections (according to a Global Assessment Question) and
measurements of change from baseline in penile blood flow.
"Alagebrium appears to have a unique mechanism of action and
significant therapeutic potential for the treatment of diabetic
erectile dysfunction," said Dr. Hellstrom. "We are eager to
continue the evaluation of alagebrium in a clinical setting for the
treatment of ED, and help the large number of patients who are not
sufficiently responsive to current ED treatment." Alagebrium has
demonstrated the ability to reverse ED in a preclinical model of
diabetes. A preclinical study(2) presented by Mustafa F. Usta, M.D.
at the 11th World Congress of the International Society for Sexual
and Impotence Research in Buenos Aires in October 2004 demonstrated
that the administration of alagebrium resulted in a significant
improvement in erectile function, as well as a decrease in serum
and tissue A.G.E. levels. In addition, alagebrium normalized other
diabetes-induced pathologies associated with ED, an effect not seen
with PDE5 inhibitors. According to the investigative team, these
data are unlike results for currently marketed ED drugs in similar
experiments, particularly due to a beneficial effect on the
function of the corpus cavernosum. The results of this preclinical
study have been submitted for publication in a peer-reviewed
medical journal. In prior clinical and preclinical studies,
alagebrium appeared to have a remodeling effect on the
cardiovascular system(3) as well as a positive effect on systolic
hypertension(4) and vascular compliance.(5) The drug is currently
in Phase 2 studies in patients with hypertension and heart failure.
In addition, it is being studied for its effect on endothelial
dysfunction, a condition also linked to ED. Understanding the Link
between Erectile Dysfunction and Vascular Disease Erectile
dysfunction is defined as the persistent inability to attain and
maintain an erection sufficient to permit satisfactory sexual
intercourse. ED has been reported to affect as many as 20 to 30
million men in the United States and 152 million men worldwide,
according to the National Institutes of Health. The risk for ED
increases progressively with advancing age, with an estimated 54
percent of men ages 65 to 70 reporting some degree of impotence
(Nicolosi, 2003). It is believed that 85-90 percent of ED cases are
related to a physical or medical condition, while 10-15 percent are
due to psychological causes. Many studies have identified ED as an
early indicator of cardiovascular diseases, including hypertension,
heart attack and stroke, and point to the underlying dysfunction of
the arteries and vascular system as a principal cause. ED is
commonly associated with a number of other conditions frequently
occurring in aging men, including prostatic hypertrophy, arterial
hypertension, ischemic heart disease, peripheral vascular disease,
atherosclerosis, hyperlipidemia, and diabetes mellitus. An
estimated 30-40 percent of diabetic and aged patients with ED do
not receive benefit from currently available drugs, and patients
with diabetes or severe vascular disease are among the most
refractory to such treatments. This occurs, in part, because the
corpus cavernosum, the structure in the penis that acts as an
expandable reservoir for blood, has become significantly glycated
and fibrotic, unable to properly dilate due to the accumulation and
crosslinking of pathological molecular structures called advanced
glycation end-products (A.G.E.s)(6). A.G.E.s have been implicated
in the fibrosis and stiffening of tissues and organs throughout the
body and have been shown to contribute to many inflammatory
processes. A.G.E.s have been demonstrated to impair erectile
function in diabetes by affecting the functional capabilities of
the corpus cavernosum and by interfering with the production of the
natural penile vasodilating agent, nitric oxide (NO) via their
effects on endothelial and neuronal nitric oxide synthases. "The
Phase 2 ED trial provides Alteon with a clinical development
pathway that is not only supportive of our ongoing programs in
cardiovascular diseases, but also fits well with our strategic and
financial objectives," said Kenneth I. Moch, President and CEO.
About Alteon Alteon is developing several new classes of drugs that
have shown the potential to reverse or slow down diseases of aging
and complications of diabetes. These compounds appear to have an
impact on a fundamental pathological process caused by the
progressive formation of protein-glucose complexes called Advanced
Glycation End-products (A.G.E.s). The formation and crosslinking of
A.G.E.s lead to a loss of flexibility and function in body tissues
and organs and have been shown to be a causative factor in many
age- related diseases and diabetic complications. Alteon has
created a library of novel classes of compounds targeting the
A.G.E. pathway. Alteon's lead compound alagebrium chloride
(formerly ALT-711) , the only A.G.E. Crosslink Breaker in advanced
human testing, has demonstrated safety and efficacy in several
Phase 2 trials and is actively being developed for systolic
hypertension, heart failure and erectile dysfunction. Over 1200
patients have been involved in alagebrium's human clinical trials
to date, of whom approximately 900 have received active compound.
Ongoing clinical trials include the Phase 2b systolic hypertension
trial, SPECTRA (Systolic Pressure Efficacy and Safety Trial of
Alagebrium), the Phase 2a heart failure trial, PEDESTAL (Patients
with Impaired Ejection Fraction and Diastolic Dysfunction: Efficacy
and Safety Trial of ALagebrium), the Phase 2 trial EMERALD
(Evaluation of Alagebrium in Erectile Dysfunction in Diabetic Males
on PDE5 Inhibitors), as well as a fourth trial exploring mechanism
of action in endothelial dysfunction. For more detailed information
about alagebrium, please visit the scientific publications section
of the Alteon website, http://www.alteon.com/. Any statements
contained in this press release that relate to future plans, events
or performance are forward-looking statements that involve risks
and uncertainties including, but not limited to, those relating to
technology and product development (including the possibility that
early clinical trial results may not be predictive of results that
will be obtained in large-scale testing or that any clinical trials
will not demonstrate sufficient safety and efficacy to obtain
requisite approvals or will not result in marketable products),
regulatory approval processes, intellectual property rights and
litigation, competitive products, ability to obtain financing, and
other risks identified in Alteon's filings with the Securities and
Exchange Commission. The information contained in this press
release is accurate as of the date indicated. Actual results,
events or performance may differ materially. Alteon undertakes no
obligation to publicly release the result of any revision to these
forward-looking statements that may be made to reflect events or
circumstances after the date hereof or to reflect the occurrence of
unanticipated events. (1) "Vardenafil for Treatment of Men with
Erectile Dysfunction: Efficacy and Safety in a Randomized,
Double-Blind, Placebo-Controlled Trial." Journal of Andrology, Vol.
23, No. 6, p. 763-771. November/December 2002. Wayne J.G.
Hellstrom, et al. (2) "Delayed Administration of ALT-711, but not
of Aminoguanidine, Improves Erectile Function in Streptozotocin
Diabetic Rats: Curative Versus Preventive Medicine." Abstract
presented at the 11th World Congress of the International Society
for Sexual and Impotence Research, October 2004. Mustafa F. Usta,
Muammer Kendirci, Trinity J. Bivalacqua, Serap Gur, Wayne J.G.
Hellstrom, Neale A. Foxwell, Selim Cellek. (3) "Effect of ALT-711,
a Novel Glucose Cross-link Breaker, in the Treatment of Diastolic
Heart Failure." Poster presentation, European Society of Cardiology
Congress 2003. Dalane W. Kitzman, Michael Zile, William C. Little,
W. Gregory Hundley, Terrence X. O'Brien, Robert C. deGroof. (4) "A
Clinical Trial of an A.G.E. Cross-link Breaker, Alagebrium Chloride
(ALT-711), in Systolic Hypertension." Abstract presented at the
American Society of Hypertension Nineteenth Annual Scientific
Meeting, May 19, 2004. George L. Bakris, Alan Bank, David C. Kass,
Joel Neutel, Richard Preston. (5) "Improved Arterial Compliance by
a Novel Advanced Glycation End- Product Crosslink Breaker."
Circulation: 2001; 104: r8-r14. David A. Kass, Edward P. Shapiro,
Miho Kawaguchi, Anne R. Capriotti, Angelo Scuteri, Robert C.
deGroof, Edward G. Lakatta. (6) "The Protective Effect of
Aminoguanidine on Erectile Function in Streptozoticin Diabetic
Rats." J Urol 2003 Oct; 170(4 Pt 1):1437-42. Usta MF, Bivalacqua
TJ, Yang DY et al. DATASOURCE: Alteon Inc. CONTACT: Susan M.
Pietropaolo, Director, Corporate Communications & Investor
Relations, Alteon Inc., +1-201-818-5537, Web site:
http://www.alteonpharma.com/
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