Agent for Pancreatic MRI Shown to Improve Image Quality

The study's coprimary endpoints were achievement of a statistically significant improvement in sensitivity of detection of abnormalities with a loss in specificity of less than 7.5% by two of the three central radiologists reading the MRI images. In this study, all three radiologists achieved a clinically and statistically significant improvement in sensitivity (all radiologists p < 0.0001) with minimal loss in specificity (all radiologists < 7.5%). Moreover, the RG1068-MRI images revealed highly significant improvements on image quality (all radiologists p < 0.0001) and confidence in the diagnostic findings (all radiologists p < 0.0001), when compared to MRI alone. There were no serious adverse events (SAEs) or unscheduled days of hospitalization associated with the RG1068-MRI procedures compared to 55 SAEs and 236 days of unscheduled hospitalization associated with the ERCP procedures.

"This study demonstrated that RG1068 improves the identification of patients with pancreatic disease and allows the radiologist to render a more highly confident diagnosis to the gastroenterologist,” stated Dr. Stuart Sherman, MD, professor of medicine and radiology at Indiana University School of Medicine (Indianapolis, USA) and clinical director of gastroenterology and hepatology, and the lead investigator of this study. "RG1068 has the potential to significantly increase a physician's ability to confidently triage their patients, to improve planning for indicated ERCP and pancreatic surgery and will be an important aid in avoiding unnecessary ERCP procedures which are potentially harmful for patients.”

"We are pleased with the strongly positive results of this study which support the use of RG1068-MRI as a safe, noninvasive approach to the identification of pancreatic abnormalities,” stated Walter C. Herlihy, president and chief executive officer of Repligen Corp. (Waltham, MA, USA), the manufacturer of the compound. "We intend to request a meeting with the FDA to review these results and to discuss our plan to file a New Drug Application [NDA].”

The study was a multicenter, baseline controlled, single dose evaluation in which 258 patients enrolled at 29 clinical sites within the United States and Canada received an MRI of the pancreas with and without RG1068, and separately an ERCP. The MRI images were randomized and independently reviewed by three radiologists for assessment of the presence or absence of 10 prespecified pancreatic duct abnormalities, image quality, visualization of the main pancreatic duct, and confidence in diagnostic results. The study's coprimary endpoints were an improvement in sensitivity of identification of structural abnormalities of the pancreatic ducts using RG1068 in combination with MRI in comparison to MRI alone with minimal loss in specificity (< 7.5%). The study design used ERCP as the diagnostic reference for determination of structural abnormalities.

The analysis of the phase-3 radiographic images was a "re-read,” which was agreed to by the US Food and Drug Administration (FDA) and European Medicines Agency based on the determination that the original analysis was flawed and therefore inconclusive due to deficiencies in performance by the contract research organization overseeing the original analysis. A new contract research organization and three new radiologists were hired to conduct the re-read.

RG1068, a synthetic version of human secretin, stimulates the secretion of pancreatic fluid into the pancreatic ducts, thereby filling the ducts with water, which improves the ability to visualize pancreatic abnormalities. Identification of pancreatic duct abnormalities is important in the identification of cause and potential treatment options for diseases such as pancreatitis.

The FDA has granted RG1068 Orphan Drug status and Fast Track Designation, a process designed to facilitate the development and accelerate the review of drugs that treat serious diseases and fill an unmet medical need based on the need for safer, noninvasive tests to diagnose pancreatic disorders. There are about 300,000 MRI procedures performed in the United States and Europe yearly that could directly benefit from the addition of RG1068.

Related Links:
Indiana University School of Medicine
Repligen