BioWorld International Correspondent
LONDON - PPL Therapeutics plc is abandoning plans to spend £42 million (US$67 million) on a manufacturing plant for recombinant alpha-1-antitrypsin, resulting in the write-off of £7.5 million it already invested in the project.
AAT, for the treatment of hereditary emphysema and cystic fibrosis, is partnered with Bayer's Biological Products division, the major supplier of plasma-derived AAT. PPL, based in Edinburgh, said it is discussing with Bayer alternative arrangements for manufacturing AAT, including the use of a contract manufacturer. PPL has a pilot AAT plant that can produce sufficient product for clinical trials.
Bayer is developing recombinant AAT, produced from the milk of transgenic sheep, as an inhaled product to deliver the treatment directly to the lungs and improve patient acceptability, compared to plasma-derived product, which is administered intravenously. However, development was held up last March when the FDA requested further analyses after patients withdrew from a Phase II safety study.
Since then the two companies "have extensively studied the route of admission, dose, purity and formulation issues," PPL CEO Geoff Cook said. "The result is a revised manufacturing process, leading to an extremely high-purity product."
However, he added, "The building of a £42 million, debt-financed manufacturing plant represents too great a risk to the future viability of PPL."
As well as modifying the formulation of the product, Bayer also is looking at improving the delivery of AAT using an innovative inhaler. Consequently, the development program has been revised to give a launch date of 2007.
As a result of the delays to AAT development, Bayer and PPL are discussing changes to the original agreement, signed in August 2000. Cook said that could include acceleration of milestone payments to reflect the balance of risk in the program.
The delay means that PPL's first product to market, Fibrin-1, a tissue sealant used to stop bleeding during surgery, will not be based on the transgenic clone technology that made the company famous. Fibrin-1 is derived from human plasma, though PPL does have a program to produce the compound transgenically. It is seeking to register Fibrin-1 as a medical device in Europe, a shorter regulatory haul than registering a new drug, and so believes it will launch in 2005.
PPL has cut cash burn from £900,000 to £600,000 by ditching the AAT plant, and also through the spinout of its U.S operations.