Discovery Laboratories now believes March 2012 could mark the end of an almost eight-year regulatory odyssey to secure FDA approval of its synthetic surfactant Surfaxin (lucinactant).

FDA has set a March 6, 2012 user fee deadline for action on Discovery's response to an April 2009 "complete response" letter that focused on chemistry, manufacturing and control issues, the company said Sept. 28. The company submitted its response on Sept. 2.

Discovery is seeking approval for prevention of respiratory distress syndrome in premature infants. If approved, lucinactant would be the first fully synthetic, peptide-containing surfactant replacement therapy for use in neonatal medicine, providing an alternative to animal-derived surfactants that are the current standard of care, the company said.

The NDA was originally submitted in April 2004 but is now in its fifth review cycle, having been the subject of three "approvable" letters between February 2005 and May 2008, and a "complete response" letter in April 2009.

The last letter focused on validation of a quality control release and stability test used to demonstrate the product's biological activity ('Will fourth action letter be the charm for Discovery's Surfaxin?' Pharmaceutical Approvals Monthly, April 2009).

Biological activity of the Surfaxin used in the Phase III program, which was conducted from 2002-2004, was shown in a pre-term lamb model. However, the currently preferred biological activity test model is fetal rabbits.

Discovery said that to satisfy the agency's "complete response" letter, it had to improve and validate its fetal rabbit biologic activity test and show concordance with the pre-term lamb model by testing current-day product using both models and comparing the results ([A#06101119007]).

Discovery now believes it has produced data sufficient to satisfy FDA. "We believe that this represents concordance between the two models," Senior Vice President of Research and Development Russell Clayton said during a Sept. 28 conference call.

Don't Look For An AdComm

Clayton said he did not expect FDA to convene an advisory committee on the Surfaxin application.

Advisory committee reviews are generally held to discuss clinical efficacy or safety questions, he noted. "This is very cut and dried, a chemistry and manufacturing control issue. This is a quality specification issue, and there would be no precedence and no grounds for an FDA advisory panel on this question."

However, the company is awaiting pre-approval site inspections of facilities in Totowa, N.J. and Warrington, Pa., and remains in a "constant state of inspection readiness," Clayton said.

Surfaxin holds orphan drug designation. However, its long regulatory path serves as a cautionary tale for sponsors that drugs intended for rare diseases are not guaranteed a smooth route to approval (Also see "Pharma Industry Pushes A Broadened Meaning For “Orphan”" - Pink Sheet, 19 September, 2011.).

- Sue Sutter (s.sutter@elsevier.com)

Will March 2012 Mark The End Of Regulatory Limbo For Discovery's Surfaxin?

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