Orlando, FL - A new investigational
drug for isolated systolic hypertension (ISH), ALT-711, looked
promising in a safety and pharmacology study presented here
today during the late-breaking session. The drug, which was
developed by Alteon, is the first product to prevent
ISH by targeting stiff vessels, the company says. In the Phase
IIa study, presented by Dr David Kass (Johns Hopkins
Medical Institute), ALT-711 produced a consistent decline
in pulse pressure and an increase in large artery compliance
in older people with stiffened cardiovasculature.
One of the natural parts of the aging process is that collagen
and elastin - which maintain cardiovascular elasticity - are
prone to the formation of advanced glycosylation end-product
(AGE) crosslinks, leading to stiffening of the blood vessels
including the large arteries. This loss of flexibility in
the vasculature leads to an increase in the arterial pulse
pressure and the development of ISH, which substantially increases
the risk of cardiovascular disease and death. As well as being
a part of the aging process, the formation of these crosslinks
can also be excessive in diabetic patients. ALT-711 is a novel
thiazolium derivative that acts by breaking these AGE crosslinks.
In the study, 93 patients aged over 50 years with a systolic
blood pressure (BP) of at least 140 mm Hg and pulse pressure
of at least 60 mm Hg were randomized on a 2:1 basis to receive
oral doses of 210 mg of ALT-711 daily (n=62) or placebo (n=31)
for 8 weeks. The participants included diabetics and nondiabetics
who all had resting large artery compliances of <1.2 mL /
mm Hg and who were all maintained on existing antihypertensive
drugs. BP measurements were taken at frequent intervals and
an echodoppler was performed at baseline, day 28, and day
56.
There was a consistent and significant decline in pulse pressure
(p<0.03) in those who received the active drug, but this was
not due to a greater decline in mean BP, which makes ALT-711
different from current therapies for ISH, Kass explained.
The drug improves total artery compliance and vascular distensability
but does not alter cardiac output or systolic vascular resistance,
he noted. It was also well tolerated, with the most serious
ADR associated with ALT-711 being two incidences of AF.
ALT-711 may also have a role in diastolic dysfunction
"The first main target of this drug will be isolated systolic
hypertension, given as an addition to existing therapy," Kass
said, for which Alteon is planning Phase IIb trials with the
compound that will start later this year. ALT-711 may also
have a role to play in diastolic dysfunction "a condition
for which there are few agents," Kass noted, adding that the
drug has shown some increase in diastolic distensability of
the heart in animals.
Alteon is believed to be looking for marketing partners for
ALT-711 and has already made some agreements with regard to
certain Asian markets. Genentech is believed to be interested
in US rights to the compound.
Lisa
Nainggolan
lisa@conceptis.com
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