Changing of the Change Agents: Exit Wyeth’s Ruffolo, Enter OrbiMed’s Dolsten

We just heard the news that Bob Ruffolo, Wyeth’s R&D boss, is retiring.

A few points to make: first, from our auslander’s point of view, Ruffolo took a Wyeth research group which had already been significantly improved in the almost reverse takeover by the former Genetics Institute crowd (including its head of R&D Pat Gage) and made it a lot more business-like.

Ruffolo is not an executive to suffer fools (or those he thought fools) gladly. He rubbed a lot of people the wrong way – including colleagues running competitive R&D organizations, who didn’t like his outspokenness. And he was a particularly harsh and public critic of the FDA (at least when he talked with us – as you can read in The RPM Report here)

But he ran an organization which got stuff done. In the otherwise horribly dry year of 2007, Wyeth managed to push through two drugs (Torisel and Lybrel) – punching far above its R&D weight (Wyeth is on the small side of Big Pharma’s R&D organizations).

Wyeth is already ahead of the game this year, with two approvals, both of which your blogger had – incorrectly – written off (and we weren’t alone): Relistor (methylnalrexone), which they’d licensed from Progenics, and Pristiq, which is an isomer of their near-patent-expired anti-depressant Effexor. Pristiq in particular ran into FDA trouble last year, with the agency dinging it twice – first for its major depression indication, then for its use for post-menopausal hot flashes. Still hasn’t been approved for the latter – but scooted in on the former.

And Ruffolo has been the outspoken exponent of the statistical strategy of R&D – that for all the theories on how to improve the odds of drug discovery and development, with new markers and “model” diseases (á la Novartis – see an IN VIVO discussion here), ultimately R&D is a numbers game. You’ve got to put a certain number of compounds in the front end to get out a set number at the back end.

Science isn’t making us any better at improving those odds, Ruffolo would almost take pride in pointing out. It was Ruffolo, speaking at Windhover’s Pharmaceutical Strategic Alliances meeting in 2005, who, at least to our knowledge first among major R&D chiefs publicly, noted that attrition rates in Phase II were going up. Before you knew it, everyone was talking about it. And Ruffolo kept insisting that the only real solution to the attrition problem was to add in more compounds.

So now enter Mikael Dolsten, the former head of Boehringer Ingelheim research, whom not so long ago the IN VIVO Blog had named as a potential candidate for the top R&D job at Pfizer. (OK – we spelled his name wrong there. We may be spelling it wrong now. But we’re not alone – either Wyeth spelled it wrong in their PR (they use an “h” in Dohlsten) or Boehringer spells it wrong in theirs (they leave out the “h”).

In the brief interregnum between leaving Boehringer and landing at Wyeth, Do(h)lsten parked himself as a private equity partner at the OrbiMed, the health-care focused investment firm. Which leads us to speculate: damned few Big Pharmas are going to be able to pay themselves for all their development programs, a fact that most of them are as yet unwilling to admit. Project financing is eventually going to play a role in this game.

When we first wrote about Dolsten, one recruiter told us he was a “change agent.” So was Ruffolo, of course. But Dolsten’s few months at OrbiMed could make him a change agent of a very different kind.