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Secretin Clinical Data Presented at Autism Society
of America Annual Meeting
Meta-Analysis of Four Phase
1 Studies Shows Statistically Significant Treatment Effect
NEEDHAM, MA - July 20, 2001 - Repligen Corporation (Nasdaq: RGEN) today presented data from
its Phase 2 clinical trial of secretin in autism at the annual meeting of the
Autism Society of America in San Diego. The data showed that patients treated
with secretin had an improvement in symptoms over the eight-week period of
the trial using multiple types of assessments, which was particularly evident
in a subgroup of patients defined by two biomarkers. The Company also
presented a meta-analysis of four previously published Phase 1 studies
involving smaller numbers of patients and fewer doses of secretin. In the
four Phase 1 studies, clinical "responders" were defined with a
Clinical Global Impression of improvement, the Preschool Language Scale,
parental reports of improvement and the Childhood Autism Rating Scale
respectively. In the meta analysis, responder data from the four studies was
pooled to assess the rate of clinical response to secretin compared to a
placebo. The outcome of this analysis showed a greater number of patients
with a clinical response to secretin compared to placebo, a difference which
was statistically significant (p=0.02).
"The pooled data from these four Phase 1 studies provide evidence of
a secretin treatment effect," stated Walter Herlihy, President and CEO
of Repligen. "This result is remarkable given the preliminary nature of
these Phase 1 studies including short duration, limited dosing, heterogeneous
patient populations and the use of assessment tools which were designed
solely for the diagnosis of autism."
The results from Repligen's Phase 2 clinical trial demonstrated a
significant treatment effect of secretin in the entire patient population
using the parental Clinical Global Impression scale (p=0.02). Further
analysis defined two biomarkers for which 51% of the patient population had
values in the normal range. In this subgroup of 64 patients, there was a
statistically significant effect of secretin by four endpoints including
social function as determined with the Autism Diagnostic Observation Schedule
(p=0.016), and the Clinical Global Impression Scale ("CGI") as
determined by a professional (p=0.02) and independently by a parent
(p<0.001).
The Company also presented new data from the Phase 2 trial on a fourth
endpoint, language development as determined by the MacArthur Communicative
Development Inventory. The MacArthur language scale assesses the numbers of
words used and the number of words understood in children with minimal
language capabilities. It is based on an assessment of a child's use and
understanding of a defined vocabulary of 396 words. In the subgroup of 64
patients defined with the biomarkers, secretin-treated patients had an
average increase in receptive language of 33 words compared to a 6 word
increase in the placebo group, a difference which was statistically
significant (p=0.02).
Meta-Analysis of Clinical Response
The four published placebo-controlled Phase 1 studies enrolled a
heterogeneous patient population with a wide range of age, function level and
GI symptoms. Each study used different assessment tools to evaluate the
patients' response to secretin. The meta-analysis was carried out to
determine if secretin-treated patients had a higher response rate than
placebo-treated patients as determined with one of the assessments carried
out in these studies. The definition of a "responder" included: 1.
a Clinical Global Impression of change of "very much improved" or
"much improved" for at least one symptom in 2 of 5 clinical visits
(Sandler, A., et al, New Eng. J. Med., 1999, 341:1801), 2. an improvement on
the Preschool Language Scale of at least 4 points (Dunn-Geier, J., et al,
Dev. Med. Child Neurol., 2000, 42:796), 3. improvements in multiple symptom
domains as reported by parents (Roberts, W., et al, Pediatrics, 2001, 107(5):E71)
and 4. a clinically significant improvement on the Childhood Autism Rating
Scale (more than 4.09 points; Coniglio, S., et al, J. Pediatrics., 2001,
138:649). In all four studies there was a higher percentage of clinical
responders in the secretin-treated group than in the placebo group although
the difference was not statistically significant in any one study due to the
number of patients evaluated and the variability inherent in the
measurements. However, when the four studies are pooled together, there is a
29% clinical response rate in the four secretin-treated groups vs. a 16%
clinical response rate in the placebo groups, a difference that is
statistically significant (p=0.02). Thus, a secretin treatment effect is
evident in these Phase 1 studies despite the inherent limitations in
assessing behavioral changes in short-term trials in a heterogeneous patient
population.
Phase 2 Clinical Trial
Repligen's Phase 2 clinical trial evaluated three doses of secretin or a
placebo in 126 children, 3 to 6 years of age, with moderate to severe
symptoms of autism and reported gastrointestinal symptoms. A stool sample was
collected from each patient at the beginning of the trial and subsequently
analyzed for two proteins: calprotectin, a marker of gastrointestinal
inflammation and chymotrypsin, an enzyme released from the pancreas during
digestion. For each protein, 25-30% of the patients had an abnormal value
prior to treatment with secretin or a placebo. The ability to demonstrate a
secretin-related treatment effect was dramatically improved in the 64
patients, or 51% of the total patient population, with normal levels of both
proteins. The clinical trial was carried out at the Southwest Autism Research
Center/Phoenix Children's Hospital (Phoenix, AZ), the Rochester Institute for
Digestive Diseases and Sciences (Rochester, NY), the University of Maryland
Medical Center (Baltimore, MD), the Mayo Clinic (Rochester, MN) and the MIND
Institute/University of California, Davis (Sacramento, CA).
Repligen Corporation develops new drugs for debilitating pediatric
disorders including autism, cancer, and immune and metabolic disorders.
Repligen also manufactures and markets a set of patented products based on
Protein A, which are used by the pharmaceutical industry to produce
therapeutic antibodies. Its corporate headquarters are located at 117 Fourth
Avenue, Needham MA, 02494. Additional information may be requested from www.repligen.com.
This press release contains
forward-looking statements based on current management expectations. There
are certain key factors which could cause future results to differ materially
from those anticipated by management. Such factors include, but are not
limited to: uncertainty in the realization of future revenues, the uncertain
timelines for clinical activity, required regulatory approvals, results of
pending or future clinical trials, the Company's ability to continue to
establish collaborative arrangements with third parties; the Company's
ability to maintain financial stability; the technical risks associated with
development and manufacture of clinical products; the fact that there can be
no assurances that patents relating to the Company's potential products will
afford adequate protection to the Company, the risks of technological change
and competition, and the competitive environment of the biotechnology and
pharmaceutical industries. These factors are more fully discussed in the
Company's periodic filings with the Securities and Exchange Commission.
CONTACT:
Walter C. Herlihy, Ph.D.
President and Chief Executive Officer
(781) 449-9560, ext. 2000
Jennifer Eason (media)
Dan Klores Communication
(212) 981-5251
Isabel Cordova (investors)
The Trout Group
(212) 477-9007, ext. 13
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