* Pfizer, Astra, Glaxo all shrinking R&D spending
* Sanofi could be next to cut back
* Switzerland's Roche, Novartis more circumspect
By Ben Hirschler, European Pharmaceuticals Correspondent
LONDON, Feb 5 (Reuters) - The axe is swinging in research labs once hailed as the life blood of the drug industry, as companies conclude they are not getting enough bang for their buck.
AstraZeneca, GlaxoSmithKline and Pfizer, have all taken a knife to research and development in the past week, ditching drug discovery work that does not pay its way.
France's Sanofi-Aventis, which wraps up the pharmaceutical reporting season on Feb. 10, is another strong candidate for new research cutbacks, analysts believe.
The jury, however, is still out as to whether shrinking the research base will kill or cure Big Pharma as it struggles with falling sales and mounting pressure on margins in the face of an unprecedented wave of patent expiries.
Switzerland's two big drugmakers, Novartis and Roche, have been more circumspect about research cuts, and Novartis Chairman Daniel Vasella sees a need for balance.
"You can improve margin up to self-dissolution. You save and you save and you cut costs and cut costs -- and then you have no sales anymore and then you have a collapse," he said in a recent interview.
What is undeniable is that returns on investment in drug research over the past decade have been dismal.
The industry's output of new drugs has fallen nearly 50 percent since 1998, despite sharply increased spending, according to CMR International, a Thomson Reuters subsidiary.
Furthermore, much of the ground-breaking work is now coming out of small, nimble biotechs rather than Big Pharma. ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
Graphic showing R&D spending and new drug output:
http://graphics.thomsonreuters.com/119/GLB_PHMRD1109.gif ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
BUYING IN
That has led to calls for large companies to scrap early-stage research into conventional pill-based medicines and instead license in promising products from smaller operators.
In doing so, they would be following a successful "search and development" model adopted by mid-sized specialty pharma companies like Shire and Forest Laboratories.
The upside could be huge, according to analysts at Morgan Stanley, with every $1 invested in compounds brought in from outside delivering on average three times as much value as $1 invested in in-house research.
Shire Chief Executive Angus Russell is not surprised bigger rivals are now rethinking R&D and recognising it is development -- getting drugs through trials and approved by regulators -- that is key to commercial success, rather than early research.
"It was only a question of when, rather than if, these things happened," he told Reuters.
AstraZeneca's decision last week to cut thousands more jobs and reduce R&D costs by $1 billion over the next four years arguably takes it furthest down the externalisation road.
Plans from Glaxo to stop discovery work in pain and depression -- traditionally a mainstay of its business -- is a more targeted response.
Still, Glaxo's move will cut a swathe through laboratories in Britain, Italy, Canada, Poland and Croatia, to the dismay of some staff.
"Does anyone ever get the feeling it's a race to the bottom?" one anonymous insider commented in a blog posting, following Glaxo's announcement on Thursday.
The biggest challenges, however, face the world's largest drugmaker. Pfizer's long-term guidance suggests it plans to cut its annual R&D budget by $2-3 billion for 2012.
Those cuts will help mitigate the impact of loss of U.S. patent protection on cholesterol drug Lipitor, the world's biggest-selling drug, in November next year.
But are they wise?
RED FLAG
Sanford Bernstein analyst Tim Anderson said while Pfizer had got little from the $66 billion spent on R&D over the past decade, it might have achieved even less if it had spent less.
"As an industry where innovation lies at the core, cutting R&D should raise at least some red flags," he said.
Faced with spiralling costs, which have driven the price of getting a new drug to market to between $1 billion and $2 billion, all drugmakers have made strides to de-risk operations by taking options on outside research rather than investing everything upfront on in-house work.
The question now is how far the process can go.
"We need to see an uplift in productivity from R&D," said Mike Ward, a veteran industry watcher at Ambrian Partners.
"But you've got to be careful in terms of how hard you cut because R&D is a fragile beast at the best of times."
(Editing by David Cowell)