(Corrects name of behavior scale in paragraph 16)
* Drug missed main goal of improving social withdrawal
* Company says trial offered better idea of who would
* Plans for new trial of drug already under way
By Julie Steenhuysen
CHICAGO, May 1 The first-ever drug designed to
treat social impairments associated with autism failed to show a
benefit in a midstage trial, representing a blow to families and
to privately held drugmaker Seaside Therapeutics.
Results of the study, presented on Wednesday at the
International Meeting for Autism Research in Spain, showed the
drug known as STX209 failed to improve symptoms of social
withdrawal in a 12-month study of 150 individuals aged 5 to 21,
most with classic autistic disorder.
The drug is the first of a handful of treatments in
development that are expressly designed to correct the
genetically induced signaling problems in the brain that result
Seaside's drug STX209, or arbaclofen, works to control an
overabundance of signaling or "noise" at brain synapses by
reducing the amount of the neurotransmitter glutamate that is
available in the brain.
Other companies pursuing drugs for autism include Swiss
drugmakers Novartis AG and Roche Holding AG,
which last year licensed patents from Seaside for the use of
drugs known as mGluR5 antagonists that attack the signaling
problem in a different way.
Based on the results, however, Roche has decided to pass on
its option to develop arbaclofen, said Dr. Randall Carpenter,
president and chief executive officer of Cambridge,
Massachusetts-based company. Roche did not return calls seeking
Carpenter said Seaside will seek new partners and has
already met with the U.S. Food and Drug Administration to devise
a new study based on the current trial's findings that he
believes may yet lead to the drug's approval.
"We believe our drug works at a molecular level that
corrects signaling pathway abnormalities, circuit abnormalities
and even anatomical abnormalities," Carpenter said.
"So the real question for us is, if you have a
disease-modifying therapeutic, how would you demonstrate that in
a short-term clinical trial?" Carpenter said.
In general, individuals with autism struggle with
difficulties in communication, behavior and social interaction.
U.S. government researchers said in March that as many as one in
50 American school-age children have a diagnosis of autism,
which can range from highly functioning individuals to those
with severe speech and intellectual disabilities.
While intensive behavioral therapy has been shown to help,
there are no approved drugs that can reverse or improve core
symptoms of autism.
In the Seaside trial, the primary goal of improvements in
social withdrawal was assessed based on parent observations, and
that may have contributed to high response rates among those who
got a placebo, likely reflecting parents' eagerness to see an
Dr. Bryan King, director of the Seattle Children's Autism
Center at the University of Washington and Seattle Children's
Hospital, said the issue of a strong placebo effect has been a
problem in prior trials. "It's not uncommon at all to see a 25
to 30 percent placebo response rate in these studies," he said.
But researchers saw other signs that the Seaside drug was
having an effect. On a secondary measure of severity, which is
scored by clinicians, there was a significant difference between
those in the study on the drug and those who were on a placebo.
"This is a clinically relevant level of change," Dr. Jeremy
Veenstra-Vanderweele Of Vanderbilt University, one of the
study's key investigators, said in a webcast from the meeting.
Veenstra-Vanderweele said an analysis of the results showed
improvements in day-to-day social function, as measured on a
scale known as the Vineland Adaptive Behavior Scale.
"This is a scale that a lot of us as investigators didn't
think could move over this period of time. So this is a
potentially very exciting, novel outcome," he said.
He said the next step is to test to see if this same finding
can be observed in a larger clinical trial that specifically
targets changes in this behavior.
Carpenter said the company has collected genetic samples
from more than 400 subjects and plans to study the specific
genetic differences to get a better idea of which patients will
likely respond to the drug.
(Editing by Doina Chiacu)