FDA, EMA approve Repligen's proposal for Phase 3 re-read in RG1068 trial for pancreatic imaging

May 27 2010

Repligen Corporation (Nasdaq: RGEN) announced today that the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved the Company's proposal to re-analyze the images from our Phase 3 study to establish the utility of RG1068, synthetic human secretin, in improving magnetic resonance imaging (MRI) of the pancreas (Phase 3 re-read).  The FDA and EMA have agreed to the Phase 3 re-read based on the numerous deficiencies with the analysis of the radiographic images by the contract research organization hired to oversee analysis of the Phase 3 data.  A successful re-read of the Phase 3 data may support registration of RG1068 for MRI imaging of the pancreas.  The goal of the Phase 3 study is to evaluate the sensitivity and specificity of RG1068 in combination with MRI to improve the detection of structural abnormalities of the pancreatic ducts relative to MRI alone.  Detailed visual assessment of the pancreatic ducts is important in the assessment, diagnosis and treatment of diseases such as acute and chronic pancreatitis.

"We are very pleased with the response of the FDA and EMA to our re-read proposal," stated Walter C. Herlihy, President and Chief Executive Officer of Repligen.  "Based on the positive feedback we received from both regulatory agencies, we believe that a successful re-read may provide the basis for registration, and we have no plans to initiate additional clinical studies of RG1068 in this indication.  Pending finalization of the protocol, we anticipate completing the Phase 3 re-read by the end of the year."

Based on our discussions, we do not anticipate any changes in the primary endpoints or significant modifications to the statistical analysis plan for the study.  The EMA has requested that we add an additional secondary endpoint to document that RG1068 in combination with MRI imaging reduces the use of endoscopic retrograde cholangiopancreatography (ERCP).  ERCP is an invasive procedure used to diagnose and treat diseases of the pancreas and gallbladder.  ERCP is associated with significant morbidity, which has generated interest in the development of safer non-invasive tests to diagnose gastrointestinal disorders.  We believe that there is sufficient evidence to document that the use of RG1068 in combination with a non-invasive procedure such as MRI leads to the avoidance of unnecessary ERCP procedures.

In December, we reported the top-line results from our Phase 3, multi-center, baseline-controlled, single dose study in which 258 patients with a history of pancreatitis received an MRI of the pancreas with and without RG1068, and independently an ERCP.  The MRI images were randomized and independently reviewed by three radiologists for evaluation of pancreatic duct abnormalities, image quality, number of duct segments visualized and confidence in diagnosis.  The study's co-primary endpoints were an improvement in sensitivity of detection of structural abnormalities of the pancreatic ducts using RG1068 in combination with MRI compared to MRI alone with minimal loss in specificity (<7.5%).  The study design used ERCP as the standard for determination of structural abnormalities.  The predetermined criteria for a successful study were achievement of a statistically significant improvement in sensitivity with minimal loss in specificity from two of the three central radiologists reading the MRI images.  In this study, one radiologist achieved a statistically significant improvement in sensitivity with RG1068 (p<0.0001) while a second radiologist showed a trend but did not achieve statistical significance.

The FDA has granted RG1068 Orphan Drug status and Fast Track Designation, a process designed to facilitate the development and expedite the review of drugs that treat serious diseases and fill an unmet medical need based on the need for safer non-invasive tests to diagnose pancreatic disorders.  There are more than 300,000 MRI procedures conducted in the U.S. and Europe each year that could directly benefit from the addition of RG1068.

SOURCE Repligen Corporation