Of the top 10 pharma companies worldwide, GlaxoSmithKline looked beyond its own pipeline for new drugs most often, signing 67 in-licensing agreements in just two years, according to a Datamonitor analysis.

Pfizer came in second with 47 in-licensing deals over the same period, followed by Sanofi-Aventis (41), AstraZeneca (38) and Merck (36). At the same time, GSK and Pfizer out-licensed 15 products or technologies each, while Sanofi mostly kept its R&D discoveries under wraps; the Paris-based drugmaker signed only four out-licensing agreements. AstraZeneca did the most out-licensing of the group, signing 19 agreements, according to the analysis. Total in-licensing across all 10 companies increased by 12% in 2009.       

While pharmaceutical manufacturers continue scouting for acquisitions to replace patent losses — six of the 10 best selling drugs will suffer patent expiries in the next two years, including GSK’s Advair, IMS SVP healthcare insights Murray Aiken said today — it has become more difficult, and costly, to pick up late-stage or approved drugs. As a result, 57% of the in-licensing deals signed in ’08 and ’09 by the top 10 pharmas were for drugs in the earliest, preclinical stages of development, the analysis found.

“The structure of these early-stage deals is evolving with licensees becoming more risk-averse and placing increasing emphasis on commercial milestone payments supporting smaller upfront fees,” said Martin Adams, senior healthcare analyst at Datamonitor, in a statement.

Companies that licensed an already-approved drug in the last two years paid an average up-front fee of $187 million, according to the analysis. Phase 3 drugs carried a $102 million up-front price tag, with phase 2 and phase 1 fees averaging $59 million and $50 million, respectively. Drugs in preclinical development or earlier had lower up-front fees, averaging $21 million and $13 million at the discovery level.

“Companies of all sizes have to be far more creative and flexible in their approach to securing the best deal terms if they want to maintain healthy returns on investment and, as a result, relationships between big pharma and its partners are becoming increasingly dynamic, Adams said in the statement. “Traditional licensing deals, for example, continue to be replaced by option arrangements or heavily back-ended deal structures.”