BioWorld International Correspondent

LONDON - SkyePharma plc outlined its strategy for applying its drug delivery technologies to enter the biologics market at a research and development day in London last week, revealing it has developed sustained-release formulations of eight marketed products, including the $5 billion plus blockbuster Epoetin, interferon-alfa (IFN-alfa) with sales of $2.8 billion, Filgrastim (G-CSF) with sales of $1.7 billion and Somatropin (hGH), which had sales of $920 million in 2002.

It is ready to move its formulations of IFN-alfa and hGH into Phase I studies later this year.

"Biologics are an extraordinarily exciting opportunity," said Michael Ashton, CEO. "This is where the money will be, that's where the value will be, and we are moving there very rapidly now."

The earliest biologics are coming off patent, prompting interest in the production of generics. However, Ashton pointed out that the regulatory process for registering generic biologics remains unclear. While small-molecule generics only require analytical evidence that the molecule is the same and has the same pharmacokinetics in Phase I trials, biologics must meet additional equivalence criteria, including later-stage trials and immunogenicity studies.

"You will almost certainly need significant clinical development - possibly almost to the same extent as the original registration," Ashton said. As a result, the cost of developing a value-added protein drug, as proposed by SkyePharma, is likely to be comparable to developing a generic version.

All the products in London-based SkyePharma's biologics portfolio have reached proof-of-concept stage, and in addition to those mentioned are Saragramostim (GM-CSF), Aldesleukin (interleukin-2), Follitropin (follicle stimulating hormone) and insulin-like growth factor.

Dick Jones, senior vice president for research and development at SkyePharma's San Diego research facility, said all of these products are less than optimal in terms of dose frequency and convenience. SkyePharma's versions all have longer half lives.

"All of [SkyePharma's biologics] have a unique release profile and substantial patent protection, up to 2019 and beyond," Jones said. "We see this as a great opportunity for collaboration with biologics manufacturers."

Jones presented animal studies of SkyePharma's formulation of hGH with its Biosphere polymer delivery system, showing plasma concentrations of the drug were maintained for 14 days. Biosphere drugs are formulated as a dry powder that is reconstituted before use and is suitable for proteins that are unstable in solution.

Similarly, IFN-alfa formulated with DepoFoam, a liposome delivery system, stayed in circulation for 14 days. DepoFoam is suitable for proteins that are stable in solution.

Ashton said talks with potential partners are ongoing.

"There is enormous interest in getting access - we need to make sure we link up with the right partners," he said.