Pfizer spent $800M on a cholesterol drug — it raised mortality by 60%

Torcetrapib was a cholesterol drug developed by Pfizer, the world's largest pharmaceutical company. It was designed to raise HDL (good) cholesterol by inhibiting CETP, a novel mechanism that had never been proven in a drug before. Pfizer invested over $800 million in its development, making it one of the most expensive R&D projects in the company's history, and built a dedicated manufacturing plant in Ireland in anticipation of approval.

The ILLUMINATE trial was a Phase III study enrolling 15,000 patients, half receiving torcetrapib combined with atorvastatin (Lipitor) and half receiving atorvastatin alone. On 2 December 2006, Pfizer halted the trial early after an independent data-monitoring committee found that the torcetrapib group had 82 fatal events versus 51 in the control group — a 60% increase in all-cause mortality. The drug also raised patients' blood pressure, cancelling out any benefit from its cholesterol effects.

The failure wiped out $800 million in R&D spending and the value of the Ireland manufacturing facility. Pfizer's stock fell 11% on the news. The collapse was especially damaging because torcetrapib had been considered Pfizer's most promising pipeline drug to replace Lipitor, its blockbuster cholesterol treatment that was approaching patent expiry. The case became the most cited example of the risk in pharmaceutical R&D — a drug that looked perfect on the biomarker but failed catastrophically in the patient.