The FDA tapped Discovery Laboratories Inc.'s Surfaxin for acute respiratory distress syndrome as the fast-track product to take up the slot in the pulmonary and allergy drug products division of the agency's Continuous Marketing Application Pilot 2 Program.
Meanwhile, Surfaxin - synthetically engineered to mimic natural human surfactant as a replacement therapy - is on track for a new drug application filing by March for respiratory distress syndrome (RDS) in premature infants, said Robert Capetola, president and CEO of Doylestown, Pa.-based Discovery Labs.
Given the "compelling" nature of Phase III data, he said in a conference call, the FDA might award Surfaxin priority review. "I caution you not to expect that, but it's certainly a possibility," Capetola said.
The company's stock (NASDAQ:DSCO) closed Thursday at $11.80, up 56 cents.
Under the FDA program, "frequent and intimate" interaction with the agency as Discovery Labs moves Surfaxin through development is hoped to move the process along even more quickly, John Cooper, chief financial officer of Discovery Labs, told BioWorld Today.
"One [aspect] is the development program itself, but another is clearly delineating the proper endpoints," he said.
Most companies work with the FDA to do that anyway, but acute respiratory distress syndrome (ARDS) in adults is tricky, Cooper said, because it "comes from a number of different problems that affect the lung. It could be aspiration of gastric content or it could be smoke inhalation, but the most likely problems are from things like sepsis or pneumonia. So what's the proper endpoint one wants to use?"
The customary ARDS endpoint used to be mortality, Cooper said, but "a patient can get ARDS from so many different situations that the drug could have been effective and the mortality came from a different situation. Recently, the FDA is accepting the incidence rate of being alive and off the mechanical ventilator at day 28."
Regardless of how the patient ended up with ARDS, Cooper said, "our goal is to clean out the lung" and "remove that inflammatory debris," so the patient can breathe.
"We also do it in what's called segmental lung loss," he said. "A pulmonologist is at the bedside of the patient, and we wash out the lung segment by segment. If you try to wash out the lung with water or saline, you'll drown the patient."
In ARDS patients, the lungs are polluted with foreign substances. In RDS babies, "their lungs haven't developed because they haven't produced their own surfactant, the air sacs are collapsed and they can't breathe," Cooper said. Surfactants are produced naturally in the lungs and are essential for absorbing oxygen and maintaining airflow.
"The drug that's being used for ARDS is built off the same platform of technology that was applied for RDS," he said. "It's the same surfactant, with a different dilution and delivery mechanism" - which might speed development along.
"But quick is one thing, proper is best," Cooper said.
Participation in the FDA program is limited to one fast-track product per division, and it's open only to companies that have completed an end-of-Phase I meeting (or its equivalent) with the agency.
Other companies involved include Palo Alto, Calif.-based Intrabiotics Pharmaceuticals Inc., with its oral solution of iseganan hydrochloride for the prevention of ventilator-associated pneumonia. Intrabiotics' drug was chosen as the fast-track product in the anti-infectives division.
Discovery Labs' two Phase III trials with Surfaxin for respiratory distress syndrome in premature babies proved the drug was 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.)
A more recent trial tested 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. (See BioWorld Today, Nov. 26, 2003.)
Surfaxin also shone with regard to endpoints other than the primary one, Capetola said in the conference call.
He noted the "dominant endpoint news in neonatology for the last 10 years, and that is the endpoint of being alive without chronic lung disease, also called bronchopulmonary dysplasia at day 28 and 36 weeks post-conceptual age."
Surfaxin proved statistically significant to Exosurf at both measures, "and was on the right side in terms of benefit vs. Survanta. No compound has ever done that in terms of bronchopulmonary dysplasia against a protein-containing surfactant," Capetola said, and more data are expected to be published in a scientific journal.
Other Surfaxin trials include a Phase II study for ARDS in adults; one Phase III and one Phase II study for meconium aspiration syndrome in full-term infants; and a Phase Ib study for asthma.
"Ultimately, our goal is to displace the animal-derived surfactants," Capetola said, adding the company intends "in the very near future to be able to assess the financial impact of this data. The market is perhaps much larger than with the animal-derived products, even in the RDS indication alone."