Discovery Laboratories, Inc., announced positive primary endpoint results of its phase 3 clinical trial of Surfaxin for Respiratory Distress Syndrome (RDS) in premature infants. The trial's independent Data Safety Monitoring Board (DSMB) informed the study's steering committee and discovery that the trial had achieved statistical significance in its co-primary endpoints for Surfaxin versus Exosurf (a non-protein containing synthetic surfactant). Survanta, a cow-derived surfactant served as a reference arm in the trial. Discovery intends to use the results of this pivotal study, together with the successful results of an earlier RDS Phase 3 supportive study, to form the basis for a new drug application (NDA) with the US FDA in the first quarter of 2004 and regulatory applications for approval in the rest of the world.
The DSMB, comprised of leading neonatologists, statisticians and a bioethicist, were responsible for monitoring the overall safety of the trial. The DSMB informed Discovery that statistical significance was achieved in favor of Surfaxin over Exosurf for the co-primary endpoints of RDS-related mortality through 14 days of life and the incidence of RDS at 24 hours of life. The DSMB also determined that the trial, originally estimated to enroll approximately 1500 patients, could be concluded at 1294 patients.
The DSMB noted no major safety issues during the enrollment phase of the trial. Discovery intends to announce further data relating to key safety and secondary outcome measures from this trial once such data becomes available, which is anticipated to be in the first quarter of 2004.
"More than 2.7 million premature infants are born worldwide each year at risk for serious complications or death from RDS. To treat this disease, doctors and parents are currently limited to using surfactants that are derived from pig and cow lung sources. These animal-derived therapies are clinically effective, but have inherent drawbacks. Tragically, there are hundreds of thousands of premature babies born in the world each year who need, but do not receive, effective surfactant replacement therapy," said Dr. Fernando Moya, Richard W Mithoff professor of pediatrics and director, division of neonatal-perinatal medicine at the University of Texas Medical School at Houston, a leading authority in neonatal medicine and the head of the trial's steering committee.
"For the first time in neonatal medicine, we have available in clinical trials, an engineered surfactant that has the most essential attributes of natural human lung surfactant, Surfaxin. These results are extremely encouraging for the pediatric community and represent a significant opportunity to improve the standard of care and provide treatment for RDS in premature infants around the world," continued Dr Moya.
"These are extremely exciting results and we are grateful for the dedicated efforts of our clinical investigators worldwide," said Robert J Capetola, PhD, president and CEO of Discovery. "We now have used Surfaxin to treat infants with RDS at leading medical facilities throughout North America, Central and South America, as well as in Western and Eastern Europe. As a result, Surfaxin has gained broad exposure throughout the medical community. This announcement, along with our earlier positive Phase 3 RDS supportive data, and the data from Part A of our ongoing Phase 2 Acute Respiratory Distress Syndrome trial, adds to the series of positive results demonstrated by the clinical trials of our surfactant technology. We look forward to continuing our efforts to build one of the most innovative respiratory pipelines available."
Christopher J. Schaber, Ph.D., executive vice president and chief operating officer commented, "Our immediate priority is to complete the analysis of all of the study endpoints, assemble a high quality data package to support the filing of an NDA, and submit the results of the trial for publication in a prominent peer-reviewed journal. We are pleased with the current progress of our manufacturing initiatives and will now increasingly focus on commercialization activities for the potential launch of Surfaxin."
"The neonatal community would welcome an alternative to the currently approved animal-based surfactants. Although these products represented a major advance in neonatal medicine, a number of us have always been concerned about the potential risks associated with the use of these cow- and pig-derived products," said Steven M. Donn, MD, professor of pediatrics and director of neonatal-perinatal medicine at CS Mott Children's Hospital of the University of Michigan Health System. "These data represent an important advancement in treating RDS in infants with an improved, humanized surfactant that does not have the potential to cause adverse immunological responses or transmit animal-borne diseases, based on what we have seen so far," continued Dr. Donn.
The landmark, pivotal trial was designed as a multinational, multicenter, randomized, masked, controlled, prophylaxis, event-driven, superiority trial to demonstrate the safety and efficacy of Discovery's Surfaxin, which is engineered to closely mimic the most essential attributes of human lung surfactant, over Exosurf, an approved, non-protein containing synthetic surfactant. Survanta, the leading cow-derived surfactant used in the United States, served as a reference arm in the trial. In addition to the co-primary endpoints, the study was designed to evaluate key safety parameters and secondary endpoints, which are significant complications of prematurity. These secondary endpoints and certain safety data will remain blinded in accordance with the trial protocol through 36 weeks post conceptual age and long-term follow-up.
An independent adjudication committee comprised of leading neonatologists and pediatric radiologists assessed the co-primary endpoints and certain secondary endpoints. This committee provided a consistent and standardized method for assessing primary efficacy data in the trial. As part of the overall evaluation of trial safety, the DSMB also reviewed these adjudicated endpoints.
Discovery also recently announced positive results from its supportive RDS Phase 3 study that was designed as a non-inferiority trial comparing Surfaxin to Curosurf, a pig-lung extract believed by many of the world's leading neonatologists to be the best surfactant currently approved.