Discovery Laboratories, Inc. announced that it has notified the European Medicines Evaluation Agency (EMEA) of its decision to voluntarily withdraw the Marketing Authorization Application (MAA) for Surfaxin for the prevention and treatment of Respiratory Distress Syndrome (RDS) in premature infants.
The decision to withdraw is based on recently announced manufacturing issues that Discovery has now determined can not be resolved within the MAA review timetable. Withdrawal precludes resolution of certain outstanding clinical issues, which were the focus of a recent EMEA clinical expert meeting and relate to the Surfaxin phase 3 clinical trials (including the design and lack of comparison to Curosurf, the leading surfactant in Europe), that also may not have been resolvable within the current MAA review timetable. As a consequence, additional clinical trials may be required to support approval of Surfaxin for RDS in Europe through the centralized procedure.
Discovery's New Drug Application to the United States Food & Drug Administration (FDA) is supported with data from Discovery's phase 3 SELECT and STAR trials. The FDA has issued Discovery a second Approvable Letter, which contains conditions that must be satisfied by Discovery prior to obtaining final US marketing approval. Consistent with previous review, the FDA does not have any clinical or statistical comments.
Discovery previously announced that certain stability parameters from the Surfaxin process validation batches had not been achieved. As a result, additional process validation batches will have to be produced, which will take longer than the allotted MAA review timetable. The European centralized regulatory procedure does not provide a mechanism for placing an application on hold at this stage in the review process, or allow a company to add new information to the MAA. Discovery intends to have further discussions with the EMEA and develop a strategy for potential Surfaxin approval in Europe.
Discovery submitted the MAA in October 2004. The MAA submission was supported, in large part, by data from Discovery's two positive Phase 3 RDS clinical trials. The SELECT study was a pivotal, landmark, adjudicated 1294 patient study that demonstrated Surfa0in's superiority to Exosurf, a non-protein containing synthetic surfactant. Survanta, a cow-derived surfactant and the leading surfactant used in the United States, served as a reference arm in the SELECT trial. The multinational SELECT study demonstrated that Surfaxin was significantly more effective in the prevention of RDS and also improved survival (continuing through at least one year of life) and other outcomes versus comparator surfactants. Discovery also conducted a 252 patient supportive study (STAR) that demonstrated Surfaxin's non-inferiority to Curosurf, a pig-derived surfactant and the leading surfactant used in Europe.
Surfaxin is a precision-engineered, peptide-containing, synthetic surfactant that is designed to closely mimic the function of natural human lung surfactant and represents a potential alternative to animal-derived surfactants.