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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