Date: Wed, 4 Apr 2001 14:31:24 -0700
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Subject: Repligen Reports Positive Results of Secretin Trial/ Beyond the
Wall: Book
FEAT DAILY NEWSLETTER Sacramento, California http://www.feat.org
"Healing Autism: No Finer a Cause on the Planet"
______________________________________________________
April 4, 2001 Search www.feat.org/search/news.asp
Also: Beyond the Wall: Personal Experiences with Autism
and Asperger Syndrome - Book Review
Repligen Reports Positive Results of Secretin Trial
[From a company press release.]
http://www.northernlight.com/arun?sacl=uvm55jYsf2ija&sastdt=200104031830
<--- address ends here.
PRNewswire -Repligen Corporation (Nasdaq: RGEN) announced today
initial results from a Phase 2 clinical trial of human synthetic secretin in
young children with autism. The double-blind, randomized, placebo-controlled
trial evaluated the safety and efficacy of three administrations of secretin
or a placebo at three week intervals in autistic children. An initial
analysis indicates that secretin produced a statistically significant
improvement in autism symptoms as measured with a parental Clinical Global
Impression Scale (p = 0.02).
The trial enrolled 136 children 3 to 6 years of age at five U.S.
clinical centers. The diagnosis of autism was confirmed in all patients with
the Autism Diagnostic Interview. The children who participated in the
clinical trial had moderate to severe symptoms of autism and reported
gastrointestinal symptoms. There were 66 evaluable patients in the secretin
group and 60 in the placebo group.
Two types of observations were used to assess changes in the symptoms
of autism: evaluations of symptom changes over an eight week treatment
period by a parent and evaluations prior to the first dose and approximately
two weeks after the third dose based on direct observation of the patient
during a 60 minute clinical visit by a psychologist ("rater").
A principle parent-based evaluation was the Clinical Global Impression
Scale (CGI), an assessment of a patient's behavioral changes from baseline.
A CGI is based on a 7 point scale in which 1 = "very much improved" and 7 =
"very much worse". The parental CGI showed a statistically significant
improvement in the secretin-treated group versus the placebo-treated group
(p = 0.02). In a responder analysis, a total of 12 patients (18%) were rated
as 1= "very much improved" in the secretin group versus 3 (5%) in the
placebo group, a difference which is statistically significant (p = 0.02).
There were a total of 44 patients rated as either "very much" or "much"
improved (CGI = 1 or 2). Of this group, 28 were secretin-treated and 16
received placebo (p = 0.09).
A principle rater-based evaluation and the primary endpoint for the
trial was the Childhood Autism Rating Scale (CARS). CARS score changes in
the secretin-treated group were not significantly different compared to the
placebo group. In a further analysis, clinical responders were defined as
patients with a CARS score decrease of 10 or more points. There were 12
responders (18%) in the secretin-treated group versus 5 responders (8%) in
the placebo group (p = 0.12). Analysis of the change in CARS scores showed a
large variation from baseline to week eight which was independent of drug
treatment. This suggests that many patients had significant day-to-day
variations in symptoms which were randomly captured by this measurement
tool.
"This study demonstrates that three doses of secretin produces a
statistically significant clinical response in a subset of autistic
children," stated Walter C. Herlihy, President and CEO of Repligen. "Our
study also indicates that in this patient population parental observations
over eight weeks were more sensitive to change than observations based on a
clinical visit."
The safety of secretin was also evaluated. There were no "serious
adverse events" in either the secretin or placebo-treated groups. Since
there have been anecdotal reports of hyperactivity, sleep disruption, and
increased irritability or aggressiveness following secretin treatment in
patients outside of this study, these symptoms were specifically assessed in
the initial data analysis. These four symptoms were observed in a total of
19 patients including 9 of the secretin-treated patients (14%) and 10 of the
placebo-treated patients (17%). No patient showed an immune (antibody)
response to secretin four weeks after the third dose. Additional analyses of
blood chemistries are currently in progress.
Clinical and Biological Correlations with Secretin Response
There was no bias in response to secretin attributable to patient sex,
severity of autism symptoms at baseline or the severity or nature of the
patients' gastrointestinal symptoms at baseline. There was a trend to higher
response rates in younger patients which did not reach statistical
significance (p = 0.06).
Multiple blood, urine and stool samples were collected from each
patient for analysis of parameters that may be associated with an
individual's response to secretin. Initial analysis of these samples has
indicated that there is a biological marker which defines a set of patients
for whom the effect of secretin or placebo treatment was highly variable.
The 37 patients with this marker were removed from the patient population
and the remaining 89 patients were analyzed as a subgroup (46
secretin-treated patients and 43 placebo patients). The statistical
significance for the parental CGI changed from p = 0.02 for the entire
patient population to p < 0.001 for this 89 patient subgroup.
In a further analysis, secretin responders were defined as patients
rated as "very much improved" and "much improved" (CGI = 1 or 2). In the
entire patient population there were 28 responders (42%) in the
secretin-treated group versus 16 responders (27%) in the placebo group (p =
0.09). By contrast, in the 89 patient subgroup there were 24 responders
(52%) in the secretin-treated group versus 9 responders (21%) in the placebo
group (p = 0.005). These data will be published following complete analysis
of the predictive value of this marker as a patient exclusion criteria and
an assessment of its patentability. We intend to carry out additional
analyses of the biological samples obtained in this trial to evaluate
additional biological markers which may correlate with the clinical response
to secretin.
Assessment of the Symptoms of Autism
The Clinical Global Impression is a tool commonly used to assess
patient improvements in trials in which the targeted symptom is a behavior
or cognition, e.g. depression, obsessive compulsive disorder and Alzheimer's
disease. The scale assigns a change of 1 for "very much improved", 2 for
"much improved", 3 for "minimally improved", 4 for "no change" up to 7 for
"very much worse". CGI assessments by raters and patients have been used for
the approval of numerous drugs including Aricept(R) and Cognex(R).
The CARS is a standardized instrument for the diagnosis of autism. The
administration of CARS consists of an observation of a patient for 30 - 90
minutes. The child is then evaluated on 15 specific symptoms of autism. The
scores range from 15 (no symptoms) to 60 (severe autism). Based on
literature reports, a CARS score of greater than or equal to 30 is required
for a clinical diagnosis of autism and a score above 36 indicates severe
autism symptomatology.
Clinical Trial Design and Execution
Each patient was evaluated in two visits prior to dosing during which
the diagnosis of autism was established with the Autism Diagnostic Interview
(ADI-R), the accepted standard for autism. All patients also were initially
evaluated with the Autism Diagnostic Observation Schedule (ADOS), the
Childhood Autism Rating Scale (CARS), the Gilliam Autism Rating Scale
(GARS), and a variety of other standardized instruments to assess
socialization, language, daily living skills and intelligence.
The trial enrolled 136 patients of whom 10 withdrew for a variety of
reasons. There were no drop-outs due to adverse events and the drop-out
rates were not significantly different between the secretin-treated and
placebo groups. The average age of participants in the clinical trial was
4.8 and 86% of the patients were boys, a percentage similar to that found in
the population of autism. No statistically significant differences in sex,
severity of autism or gastrointestinal symptoms existed between the
secretin-treated and placebo groups. The average age of the secretin-treated
group was 7 months older than the placebo group (p < 0.01).
The clinical trial sites were: the Southwest Autism Research
Center/Phoenix Children's Hospital (Phoenix, AZ), the Rochester Institute
for Digestive Diseases and Sciences (Rochester, N.Y.), the University of
Maryland Medical Center (Baltimore, MD), the Mayo Clinic (Rochester, MN) and
the MIND Institute/University of California, Davis (Sacramento, CA).
"We believe that this is the largest and most comprehensive clinical
trial carried out to date in autism and the only clinical trial to correlate
multiple biological measurements with the symptoms of autism," stated Walter
C. Herlihy, President and CEO of Repligen. "The clinical and biological data
obtained in this trial will enable us to plan and execute additional
clinical trials in this patient population with far greater precision than
previously possible."
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Beyond the Wall: Personal Experiences with Autism and Asperger Syndrome
[Book available from Autism Asperger Publishing Company at
www.asperger.net/wall.htm. The review is by Nancy Herndon Cale, VP Unlocking
Autism and grandmother of child with autism.]
Diagnosed with "atypical development with strong autistic tendencies"
and nonverbal until age four, Stephen Shore was viewed as "too sick" to be
treated on an outpatient basis. Stephen Shore is now completing a doctoral
degree in special education at Boston University with a focus on helping
people on the autism spectrum develop their capacities to the fullest extent
possible.
In addition, Stephen Shore serves as board president of the Asperger's
Association of New England as well as on the board of directors of several
organizations such as Unlocking Autism, Asperger Coalition of the United
States, ASA-Massachusetts Chapter.
This honest, courageous book, written by a person with
high-functioning autism and Asperger Syndrome, offers so much more than the
traditional autobiography. Drawing on personal and professional experience,
Stephen Shore, who is currently completing his doctoral degree in special
education at Boston University, combines three voices to create a touching
and, at the same time, highly informative book. The autobiographical voice
tells the story of Stephen's life, including his parents' frustrations with
the educational and medical communities, his adolescence and now adult
married life. The "time shifter" fills in background information about his
life that is otherwise out of the chronological order of the events being
related; finally the researcher's voice puts Stephen's personal life within
the context of the research literature on autism and Asperger Syndrome. By
using this triple lens, the book offers insights for parents, professionals
as well as individuals who have Asperger Syndrome. -- Autism Asperger
Publishing Company
"In Beyond the Wall" Stephen Shore provides an unusually interesting,
well-written and insightful autobiographical account of the life of a person
with high-functioning autism/Asperger Sydrome. This is a "user-friendly"
book: Stephen is a courteous and well-infromed tour guide, who makes our
visit with him both enjoyable and informative. Highly recommended." --
Bernard Rimland, Ph. D., director, Autism Research Institute
"Stephen Shore is a bright light in a very dark place. He held my
hand through cyberspace and helped me to understand how my grandson might
feel. By communicating with Stephen, I realized how much hope there is for
our children and adults with autism. This young man functions at a level
that enables him to not only help parents understand the actions and needs
of those in the spectrum, but is a treasure to those within the spectrum as
well.
_______________________________________________________
_NLOCKING A_TISM'S
THE POWER OF ONE!
CONFERENCE AND RALLY
WASHINGTON D.C. APRIL 25-27, 2001
The only thing missing is "U"
Go to our website: www.unlockingautism.org
and register TODAY!!!
_______________________________________________________
Lenny Schafer, Editor Catherine Johnson PhD Ron Sleith Kay Stammers
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