Addrenex Pharmaceuticals Announces Positive Phase III Clinical Results For Clonicel To Treat ADHD

A drug that diminishes the
body's hyper-reactivity to stress has been shown to significantly reduce
symptoms of attention-deficit hyperactivity disorder (ADHD) in children,
according to a phase 3 clinical trial conducted by Addrenex
Pharmaceuticals.


The study showed that the new drug, Clonicel, achieved statistically
significant improvement over placebo in reducing an aggregate of 18 ADHD
symptoms listed by the American Psychiatric Association and used by
physicians to diagnose and classify the condition.



"This is the first study to validate the potential for a long-acting
version of clonidine -- a widely used hypertension drug -- as a safe and
effective treatment for ADHD," said Moise Khayrallah, Ph.D., CEO of
Addrenex Pharmaceuticals, a small Durham start-up that initiated and
coordinated the multicenter trial.



Previous studies of clonidine have indicated that the drug diminishes
select symptoms of ADHD, but these studies have been small and
inconclusive, Khayrallah said. Moreover, clonidine carries bothersome side
effects that have limited its use, including a peak of drowsiness when the
drug is absorbed and a subsequent rebound of symptoms when drug levels
subside.



Addrenex scientists developed Clonicel to reduce these side effects and
treat specific ADHD symptoms that may occur when the body's adrenergic
system is in overdrive, producing excessive levels of the stress hormone
adrenaline. Such symptoms include emotional outbursts, mood swings,
insomnia and hyperreactivity to stress.



"We conducted a well-powered, randomized clinical trial to demonstrate
that Clonicel may be effective on its own in treating a multitude of ADHD
symptoms, with a favorable side effect profile," said Khayrallah. "We're
very excited with the positive data we obtained, and we intend for this
study to serve as part of the basis for review and approval by the FDA,
hopefully by next year."



The study showed that Clonicel was statistically superior to placebo on
the primary endpoint, the ADHD Rating Scale of 18 symptoms. Clonicel was
also statistically superior to placebo on several secondary scales
completed by clinicians and parents, including a scale that assesses
adrenergic dysregulation. The scale was designed by Joseph Horacek, M.D., a
Charlotte neuropsychiatrist and cofounder of Addrenex. Side effects were
generally mild to moderate in severity, and no serious adverse events were
reported in the study.



A total of 228 children between the ages of 6 and 17 with a diagnosis
of ADHD participated in the randomized, double-blind, placebo-controlled
trial that compared two doses of Clonicel, 0.2 mg per day and 0.4 mg per
day, with placebo. Children received either study medication or placebo for
eight weeks at one of 13 study centers nationwide.
















If Clonicel is approved by the Food and Drug Administration, the new
drug will be marketed by Sciele Pharma under an agreement signed with
Addrenex in July 2007.



The introduction of Clonicel into the ADHD market would fill a void
that currently exists in the treatment of ADHD, Khayrallah said. While
stimulants play an important role in treating ADHD, they do not address all
of the symptoms associated with the disorder and may result in unacceptable
side effects in some patients.



Because Clonicel targets receptors within the body's stress response
center -- the adrenergic system -- it may be more effective in alleviating
lesser-known symptoms that accompany ADHD, such as emotional outbursts,
mood swings, irritability and hyperreactivity to stress, Horacek said.



"We believe that Clonicel is normalizing the excess of the adrenergic
hormones that contribute to many of the symptoms of ADHD," said Horacek.



Stress hormones produce a rapid heart rate, elevated blood pressure,
sweating, temperature increases, heightened anxiety, stress and fear, he
said. Scientists have implicated an excessive stress response to a wide
array of disorders, from ADHD and Tourette's syndrome to post-traumatic
stress disorder and migraines.



Addrenex is currently developing a cadre of drugs focused on treating
these and other conditions arising from adrenergic excess, including
hypertension, menopausal flushing, pain and sleep disturbance. By mining a
library of 400 adrenergic compounds at the University of Nebraska Medical
Center, Addrenex scientists have already identified one new drug candidate,
a compound code named ADX415, to treat hypertension and other conditions.



"With the extremely positive data from our first study, we are well
under way toward our goal of regulating adrenergic excess and helping to
ameliorate medical conditions that arise from this physiologic imbalance,"
said Khayrallah.



The company is also midway through a second ADHD clinical trial testing
the effects of Clonicel together with stimulants. The goal is to determine
if the two treatments together alleviate a broader range of symptoms than
either drug alone.


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