Pharma’s Cutting Edge

Despite objections and clotures (”vote holds”) from a handful of vocal Republican critics, particularly, Senator Chuck Grassley of Iowa, the U.S. senate voted and confirmed the appointment of Andrew von Eschenbach as FDA commissioner on a “permanent” basis early this evening.

The nomination had been opposed by Sen. Grassley, who appears convinced that Dr. von Eschenbach is impeding Congressional oversight of FDA’s activities relating to FDA approval of Sanofi-Aventis’ antibiotic Ketek, which has been the subject of substantial controversy since its approval in 2004.

The vote approving Dr. von Eschenbach was 80 to 11, with nearly all democrats and most republicans lining up in support. 

It’s safe to say that no American would favor an executive agency running amok without sufficient Congressional oversight and checks of power.  Certainly no U.S. Senator would favor this scenario.  Sen. Grassley’s portrait of the von Eschenbach-led FDA suggests that FDA has been running amok of late, concealing secrets of national interest from Congressional oversight.  Apparently, few of his colleagues agree.

The fact is FDA operates under rigorous oversight from the likes of Senator Grassley of the Finance Committee.  This oversight has become increasingly onerous and invasive and has almost certainly distracted FDA’s leadership from its primary mission (see this September post, for example).  The U.S. Congress has an obligation to check the power of FDA, but it should leave the job of reviewing experimental therapeutics to the dedicated scientists at FDA.  Let’s hope that the confirmation of Dr. von Eschenbach is a recognition by the Senate of this distinction.

Read the press release announcing the halt of all torcetrapib clinical development here: Pfizer Media Center - News Releases.  According to Pfizer spokesman Paul Fitzhenry, as reported by the AP, an interim DMC safety review discovered 60% more deaths (82 vs. 51) among the combination atorvastatin-torcetrapib arm as compared with the atorvastatin arm in the ca. 15,000-subject ILLUMINATE trial.  Based on this “imbalance” the DMC recommended the study be stopped.  Pfizer took this recommendation and further decided to stop all torcetrapib clinical studies.

Torcetrapib, a cholesterol-ester transfer protein (CETP) inhibitor, was one of the most eagerly anticipated drugs in development.  It was also the costliest to develop; Pfizer reportedly was planning to spend over $800 million on its Phase 3 development alone.  It was a drug many analysts, including this one, deemed crucial to Pfizer’s growth prospects after Lipitor loses US market exclusivity in early 2010.

A timeline of torcetrapib milestones is found in this 2005 Pfizer press release, which announced expansion of the Irish plant Pfizer was using to manufacture the torcetrapib/atorvastatin tablets.  The drug had recently suffered a non-fatal setback when it was discovered that it raised blood pressure more than thought following Phase 2 studies.

I am neither a Pfizer investor, nor do I count Pfizer among consulting clients, yet I am terribly disappointed in this outcome.  Besides being a stark demonstration of our industry’s inability to channel late-stage investments with more predictability than could be had by relying on a coin toss, the torcetrapib failure is a hard-lost opportunity to lessen the world’s ever-mounting burden of atherosclerotic cardiovascular disease (CVD).  Whatever good comes from the torcetrapib “case” let’s not lose sight of this loss; it’s tragic in its proportions.

As for the potential good emanating from the news, surely the loss of such a large investment in time and money will serve as a reminder of the industry’s urgent needs to improve R&D decision-making and to take lessons from the financial-investment industry and practice sound product-portfolio risk management.  Eight hundred million dollar Phase 3 bets that don’t pay off will ruin this industry more assuredly than government-mandated price controls, counterfeit products, and product “re-importation” combined could.