Free The Antidote: Inside the World of New Pharma by Barry Werth

change program to fire up its labs, stoke an unexciting pipeline, and formularize a steady stream of new drugs. The Clinical Process Redesign project stretched on for eighteen months. With lingering internal resistance toward protease inhibition among Wellcome’s pro-nuc forces already entrenched, the reorganization only compounded its inertia, costing in all perhaps another year to get VX-478 to market—a year in which Agouron brought a fourth antiviral to patients.
    “They were just so unaggressive and internally deferential it drove us crazy,” Boger recalls. “I don’t know what Burroughs Wellcome would have done, but it wouldn’t have been as bad as Glaxo. They were just eternally frustrating. Every other drug in the field was perfect despite the facts. And every little scratch on the paint on our molecule knocked the value down fifty percent. It was this weird opposite of being optimistic and aggressive, such a mismatch to Vertex. We knew that we often ignored the scratches on the paint. But they would just stare at them and get depressed about how they couldn’t do anything.”
    As hopes dimmed that VX-478 would launch Vertex into the ranks ofprofitable drugmakers, the company’s aspirations shifted to other areas, most promisingly ICE and its partnership with the French drugmaker Roussel-Uclaf. Here was a wide-open opportunity, an unproven target with a highly motivated partner that shared Vertex’s passion and excitement. Anti-inflammatory drugs now more than ever were the industry’s grail, as the molecular pathways through which the immune system generates inflammation—and the seemingly endless list of painful, chronic diseases in which inflammation plays a leading part—became better understood. The ICE team quickly leapfrogged over Merck and the other leaders in advancing compounds to the clinic.
    In late 1997 Vertex and Roussel picked a clinical candidate, VX-740, derived from the original chemical series designed in five weeks by the modeling team in 1994. Since their original agreement, Roussel had been bought by German pharmaceutical giant Hoechst, which went on to buy Kansas City drugmaker Marion Merrell Dow, morphing into Hoechst Marion Roussel, or HMR, which now gave Vertex $3 million in milestone payments. As VX-740 entered preclinical testing in animals, Vertex pleasantly discovered that the Roussel team was more committed than ever. “Every partnership has its ups and down, but this one had the essentials,” Sato says. “It was an area of strategic interest and importance, and it had internal champions who stayed committed through the merger.”
    For most of the next year, while VX-478 lumbered toward approval and VX-740 sprinted toward testing in patients, Boger kept up the pressure as always to advance more compounds into development. In hepatitis C, progress was tortured and grudging, as ever. One additional intimidating and expensive obstacle for all companies weighing the costs of a full-blown program in the disease was the threat of patent litigation from Chiron, the Northern California company that discovered the virus. Chiron had chosen a novel and risky strategy for identifying the microbe, though it had no drug discovery program itself.
    After non-A, non-B hepatitis was identified in the late 1970s, and the search began for the infectious agent, numerous labs had tried—and failed—to find antibodies in the blood or grow the virus. Chiron went after the organism’s genetic material instead. Researcher Michael Houghton and his colleagues reasoned that if they could clone one or moregenes from the virus, they might be able to make proteins from them, and from the protein, an antibody. The effort took seven years, during which hundreds of millions of bacteria injected with bits of DNA were screened for a putative agent by several different approaches. It was like searching for a needle in a haystack when you didn’t know what the needle looked like, only bits of it. New