ALT-711 (the first real anti-aging drug) goes into second stage human trials

[Guest guest]

RAMSEY, N.J., July 9 /PRNewswire/ -- Alteon Inc. (Amex: ALT)

announced today that it has begun the Phase IIb SAPPHIRE (Systolic

And Pulse Pressure Hemodynamic Improvement by Restoring

Elasticity) trial of Alteon's lead A.G.E. Crosslink Breaker

compound, ALT-711, in patients with isolated systolic hypertension

(ISH). The SAPPHIRE trial will build upon positive data from a

recent Phase IIa human trial to further evaluate ALT-711's ability

to lower systolic blood pressure and pulse pressure in aging and

diabetic patients.

 

By " breaking " the pathological bonds that cause tissues, organs

and vessels to stiffen and lose function over time, ALT-711 has

demonstrated the ability to reverse certain age-related and

diabetes-related conditions. In a recent Phase IIa clinical trial

in cardiovascular disease, treatment with ALT- 711 resulted in

statistically significant and clinically meaningful effects of

increasing vascular wall elasticity and lowering pulse pressure.

ALT-711 is the most clinically advanced drug in a new class of

compounds, known as Advanced Glycosylation End-product (A.G.E.)

Crosslink Breakers, which were discovered by Alteon. No approved

drug for high blood pressure directly targets the underlying age-

related stiffening that results in ISH, and thus this condition

represents a major unmet medical need.

 

The SAPPHIRE Trial

 

In the SAPPHIRE trial, ALT-711, an orally active compound, will be

tested in 450 patients at approximately 40 sites throughout the

United States. Recruited patients will receive ALT-711 tablets

once a day for six months, in addition to their existing

medications. The study will consist of five treatment arms,

comprised of four different dose levels of ALT-711 plus placebo.

Patients enrolled in the trial must be older than 50 years of age

and have systolic blood pressure of greater than 160 mmHg and

diastolic blood pressure of less than 90 mmHg. The trial will

include both non-diabetic and diabetic patients.

 

The SAPPHIRE trial extends the range of doses and the dosing

period of ALT-711 defined in the previous Phase IIa trial. In the

Phase IIa trial of 93 patients, treatment with ALT-711 over an 8-

week period resulted in a statistically significant reduction in

pulse pressure (5 mmHg net decrease at day 56, p American College

of Cardiology meeting.

 

Consistent Results Across Species

 

Preclinical testing has clearly demonstrated the ability of ALT-

711 to reverse age-related and diabetes-related cardiovascular

disease and restore function to the cardiovascular system. " It is

important to emphasize that our data thus far has been consistent

across all species that we have tested, " said Robert C. deGroof,

Ph.D., Senior Vice President, Scientific Affairs. " In preclinical

evaluations, ALT-711 reversed stiffening of the aorta in rodents,

canines and non-human primates, similar to what recently has been

observed in humans. The SAPPHIRE trial has been designed to

confirm all of these results and to further determine effects of

ALT-711 over a longer period of time and a wider range of dosages.

It is expected to provide a solid foundation for a subsequent

Phase III program. "

 

Isolated Systolic Hypertension and the Importance of Pulse

Pressure

 

Isolated Systolic Hypertension is the most common form of

hypertension in people over age 50, and most recent statistics

estimate its prevalence at over 20 million in the U.S. alone. It

is defined as elevated systolic blood pressure (above 140 mmHg) in

conjunction with normal diastolic blood pressure (below 90 mmHg),

and is characterized by an increased pulse pressure, defined as

the difference between systolic and diastolic blood pressures. The

prevalence of hypertension increases with age, with systolic

hypertension becoming far more common than diastolic hypertension.

Yet it is the type of hypertension least likely to be well

treated, according to a recent study published in the March 16,

2001 edition of Hypertension, a journal of the American Heart

Association.

 

Traditionally, treatment of hypertension has focused on

controlling diastolic pressure. The focus on systolic pressure

began to increase in the 1990's with the results from the Systolic

Hypertension in the Elderly Program (SHEP) trial and other

epidemiological data that demonstrated that the level of systolic

blood pressure is a better predictor of cardiovascular events

including stroke, coronary heart disease, and heart failure. A

systolic blood pressure higher than 160 mmHg has been shown to

double all-cause mortality, triple cardiovascular mortality,

particularly in women, and more than double cardiovascular

morbidity in both sexes.

 

Similarly, elevated pulse pressure is increasingly being

recognized as a risk factor for cardiovascular disease. The

Framingham Study and others have demonstrated that a reduction in

pulse pressure is associated with a significant risk reduction in

cardiovascular death.

 

Current hypertension therapies, including diuretics, ACE

inhibitors, beta blockers, calcium channel blockers and

angiotensin receptor blockers have an effect on lowering both

systolic and diastolic pressures. Treatment is therefore limited,

as a patient can become hypotensive with too low a diastolic

pressure.

 

A.G.E. Crosslink Breakers, and lead compound ALT-711, may

specifically address this treatment issue. " Our results to date

suggest that we offer an opportunity to provide an option for ISH

through a novel mechanism of action, " said Kenneth I. Moch,

President and Chief Executive Officer. " We have been able to

narrow the gap between the systolic and diastolic pressures, and

we look forward to confirming these results in the SAPPHIRE trial.

As ALT-711 targets a major market with a differentiated and

clearly unmet medical need, the results from this trial will be

greatly anticipated. We are very pleased to be able to initiate

this important trial in our expected time frame, and intend to

maintain our diligence in this pursuit. "

 

A.G.E. Crosslink Breakers and ALT-711

 

Advanced Glycosylation End-products (A.G.E.s) are permanent

glucose structures that form when glucose binds to the surface of

proteins. Many of these proteins, including structural proteins

such as collagen and elastin, play an integral role in the

maintenance of cardiovascular elasticity function 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 of tissues, abnormal protein accumulation and

organ dysfunction, which together cause many of the complications

of aging and diabetes. Loss of flexibility of the vasculature

leads to isolated systolic hypertension, which creates increased

workload for the heart and may lead to myocardial hypertrophy and

heart failure.

 

ALT-711 is the first in the A.G.E. Crosslink Breaker class that

has been shown to reverse or " break " A.G.E. crosslinking, thereby

restoring more normal function to organs and tissues that have

lost flexibility. Pharmacologic intervention with ALT-711 directly

targets the biochemical pathway leading to the stiffness of the

cardiovascular system. Its mechanism of action is new and novel,

and is unrelated to that of any pharmaceutical agent either

currently prescribed or in clinical development. Importantly, ALT-

711 does not disrupt the natural enzymatic glycosylation sites 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.

 

About Alteon

 

Alteon is a leader in the discovery and development of novel

pharmaceuticals for the treatment of pathologies of aging and

diabetes, based on reversing or slowing a fundamental pathological

process caused by protein-glucose complexes called Advanced

Glycosylation End-products (A.G.E.s). The formation and

crosslinking of A.G.E.s is an inevitable part of the aging process

that leads to a loss of flexibility and function in body tissues,

organs and vessels. The company is initially developing therapies

for cardiovascular disease.

 

Alteon has created a library of novel classes of compounds

targeting the A.G.E. pathway. These include A.G.E. Crosslink

Breakers, A.G.E. Formation Inhibitors and Glucose Lowering Agents.

The Company's lead A.G.E. Crosslink Breaker, ALT-711, is being

developed for the treatment of cardiovascular disorders. ALT-711

demonstrated positive results in a recent Phase IIa clinical trial

and currently is being evaluated in the Phase IIb SAPPHIRE

clinical trial focused on isolated systolic hypertension. The

compound is also under investigation for end-stage renal disease

patients receiving peritoneal dialysis, a patient population that

has significant cardiovascular disease. ALT-711 is further serving

as a clinical prototype in other conditions where A.G.E.

crosslinking is a cause of disease, such as uropathy and diabetic

retinopathy. Pimagedine, Alteon's lead A.G.E. Formation Inhibitor,

is in active clinical evaluation in diabetic neuropathy in cats.

For more information on Alteon, visit the company's web site at

http://www.alteonpharma.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.

 

SOURCE Alteon Inc.

 

CONTACT: Susan M. Pietropaolo, Director, Corporate Communications

& Investor Relations, 201-818-5537, spietropaolo/

 

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Good Health & Long Life,

Greg Watson,

http://www.ozemail.com.au/~gowatson

gowatson

 

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Good Health & Long Life,

Greg Watson,

http://www.ozemail.com.au/~gowatson

gowatson