Repligen Corporation, a leading supplier of critical biologic products used to manufacture biologic drugs, has submitted a marketing authorization application (MAA) to the European Medicines Agency (EMA) for SecreFlo to improve detection of pancreatic duct abnormalities in patients with pancreatitis. SecreFlo (synthetic human secretin) is used in combination with magnetic resonance imaging (MRI) and is the Company’s lead diagnostic imaging product candidate.

The MAA submission for SecreFlo follows on the recent grant of Priority Review by the U.S. Food and Drug Administration (FDA) for the Company’s new drug application (NDA) for SecreFlo in the same indication. Both the MAA and NDA filings are based on positive outcomes from the company’s phase 3 clinical trial results.

“This MAA submission in the EU and the recent grant of priority review for our SecreFlo NDA in the US are important achievements that reflect the commitment of our employees and clinical investigators to this program,” said Walter C. Herlihy, Ph.D., president and chief executive officer of Repligen. “These accomplishments bring us all one step closer to the goal of providing a safe, reliable and cost-effective alternative to invasive endoscopic procedures for evaluating patients with pancreatitis.”

“We are pleased to have filed the SecreFlo MAA and look forward to working closely with the European regulators to address any questions during the review process,” stated Dr. Michael L. Hall, chief medical officer of Repligen. “We believe SecreFlo will become an important diagnostic tool to help radiologists and gastroenterologists confidently plan the best course of treatment for their patients with pancreatitis. We also believe that there are significant cost-savings associated with the use of SecreFlo and MRI versus endoscopy, which would be well-received by healthcare payers.”

We anticipate receiving a response from the EMA by March 21, following validation of completeness of the SecreFlo MAA. Pending successful validation, the EMA would then require its Committee for Medicinal Products for Human Use (CHMP) to complete a full scientific Assessment and deliver its opinion on marketing approval for SecreFlo, a process that is expected to be completed within 10 to 12 months.

As with the SecreFlo NDA in the US, the MAA was submitted to the EMA based on positive outcomes from the re-read of the company’s phase 3 clinical study. This pivotal study was a multicenter, baseline controlled, single dose study in which 258 patients were enrolled at 23 clinical sites in the US and Canada. Each patient in the study received an MRI of the pancreas with and without SecreFlo and separately underwent endoscopy as a diagnostic reference. The MRI images were randomized and independently read and reviewed by three central radiologists.

The phase 3 study’s co-primary endpoints were achievement of a statistically significant improvement in sensitivity of detection of abnormalities of the pancreatic ducts with minimal loss in specificity by two of the three central radiologists reading the MRI images. The study met its primary endpoints, demonstrating that the addition of SecreFlo to MRI resulted in a highly statistically significant improvement (p<0.0001) in sensitivity of detection of ten prespecified abnormalities of the pancreatic ducts, with minimal loss in specificity (<7.5%). All three secondary endpoints were also met, with each demonstrating highly statistically significant improvements (p<0.0001) in image quality, visualization of the main pancreatic duct and diagnostic confidence when compared to MRI alone. In addition, SecreFlo was shown to be safe and well tolerated. A radiologist’s ability to safely and more confidently identify and characterize pancreatic duct abnormalities has the potential to substantially improve “next-step” clinical decisions (patient triage) and patient outcomes.

SecreFlo is a synthetic version of the natural human hormone secretin, which is produced in the small intestine and is important in the process of digestion. Secretin naturally stimulates the pancreas to release digestive juices into the pancreatic ducts, which fill and expand with fluid that eventually empties into the intestine. When filled with fluid, the pancreatic ducts are more effectively visualized by MRI as the fluid appears white on MRI readings. SecreFlo can therefore be utilized in combination with MRI, to stimulate the release of watery fluid into the pancreatic ducts “on demand” in order to improve MRI quality and more confidently identify pancreatic duct abnormalities. Such identification is important in determining the cause and potential treatment options for diseases such as pancreatitis. There are approximately 300,000 abdominal MRI procedures conducted in the US and Europe each year that may directly benefit from the addition of SecreFlo.

In the US, the FDA has set a goal date of June 21, 2012 for completing its review of the SecreFlo NDA and delivering a decision on marketing approval. The grant of Priority Review for the SecreFlo NDA is based on the FDA’s recognition of the need for safer, noninvasive alternatives to the diagnostic use of endoscopic retrograde cholangiopancreatography (ERCP). ERCP is an invasive endoscopic procedure that has traditionally been used to examine and treat diseases of the pancreas.

More recently, the medical community has recognized the need for a safer diagnostic approach based on documented morbidity and mortality risks associated with the diagnostic use of ERCP and current practice recommendations issued by the National Institutes of Health (NIH). MRI offers a safer and noninvasive alternative to diagnostic ERCP; however, its utility is currently limited by the lack of an approved agent to enhance MRI images of the pancreatic ducts in order to achieve a definitive diagnosis. SecreFlo in combination with MRI is designed to fill this unmet need. SecreFlo has also been granted Orphan Drug status in the US, which qualifies Repligen to receive seven years of US market exclusivity for SecreFlo, if approved.