National Editor

Discovery Laboratories Inc. reaped more good news with Surfaxin, which met statistical significance in the co-primary endpoints of a pivotal Phase III trial in premature infants afflicted with respiratory distress syndrome.

The company's shares (NASDAQ:DSCO) rose $1.31 Tuesday, or 19.3 percent, to close at $8.09.

Results from the study will be combined with data from an earlier Phase III supportive trial with the surfactant, and plans are in the works to file a new drug application in the first quarter of next year.

"We feel very comfortable we're going to be able to make that [timeline]," said Robert Capetola, president and CEO of Doylestown, Pa.-based Discovery.

Surfactants, which premature babies lack, are produced naturally in the lungs and are essential for absorbing oxygen and maintaining airflow. Without surfactant, air sacs in the lungs collapse.

Synthetically engineered Surfaxin already has proved favorable when compared in a non-inferiority trial to pig-lung extract Curosurf, from Dey LP, of Napa, Calif., and Curosurf has been shown more efficacious than Infasurf, the treatment derived from calf lung manufactured by Forest Laboratories Inc., of New York. (See BioWorld Today, June 6, 2003.)

The latest trial was designed to test Surfaxin against Exosurf, a synthetic surfactant from London-based GlaxoSmithKline plc. Used as treatment in the reference arm was Survanta, the leading compound derived from bovine lungs and developed by Abbott Laboratories, of Abbott Park, Ill.

The trial's independent Data Safety Monitoring Board told the study's steering committee and Discovery Labs that statistical significance was achieved in favor of Surfaxin over Exosurf for the co-primary endpoints, and the trial, originally estimated to enroll about 1,500 patients, could be concluded at 1,294 patients.

Specifically, in one of the two endpoints - respiratory distress syndrome (RDS)-related death through 14 days - the scores were 25 out of 527 for Surfaxin (4.7 percent), 49 out of 509 for Exosurf (9.6 percent) and 27 out of 258 for Survanta (10.5 percent), yielding a "p" value for Surfaxin vs. Exosurf of 0.001.

In the other endpoint - incidence of RDS at 24 hours - the results were 207 out of 527 for Surfaxin (39 percent), 240 out of 509 for Exosurf (47 percent) and 86 out of 258 for Survanta (33 percent), resulting in a "p" value for Surfaxin vs. Exosurf of 0.006.

The DSMB noted no major safety issues during enrollment phase, and Discovery said it would disclose more about the outcomes in the first quarter of next year, when the entire body of data has been analyzed.

"When all that's clean and a lot of you think our work's over and we're gonna go fishing, not true," Capetola said during a conference call, noting that the hard work of putting the NDA together lies ahead.

Analysts have estimated the worldwide market for RDS, but it's probably larger than current guesses because of manufacturing constraints on animal-derived products that dominate the space. Surfaxin has no such limits.

"Right now, on a dollar basis, it's about $200 million," said Darren Mac, biotechnology analyst with Fulcrum Global Partners LLC in New York. "Part of [the market] is expense limited and the other part is supply limited. It's difficult to say the magnitude they can grow the market."

The opportunity is there, however. Mac told BioWorld Today only about 100,000 of 270,000 RDS cases in the developed world are treated per year. In the U.S., the number of cases is estimated at 60,000 to 70,000 per year, he said.

Surfaxin also is in Phase III trials for meconium aspiration syndrome and in Phase II trials for acute respiratory distress syndrome (ARDS) in adults, with data expected from both in the second half of 2004. Capetola called success with Surfaxin in RDS the cornerstone of building a market share in other respiratory disorders. Mac said ARDS could be particularly lucrative, and pegged the market at "well over $1 billion in the U.S. alone."

Though secondary endpoint data are yet to come, Mac said there's "not much in the way" of Surfaxin's success, details of which the company said it will seek to have published in a peer-reviewed journal.

"The other issues with the ARDS indication, especially, is immunogenicity, and foreign proteins in animal-based products," which is not a concern with Surfaxin, Mac said.

"The manufacturing side would be the only risk, but they're using the same equipment [used by the contract organization that supplied the drug in trials]," he said, and "longer term, they might set up their own manufacturing line," but this likely would come after positive data from late-stage ARDS studies.