GAME-CHANGING TRIAL
The most important test case for Vasella's ideas may turn out to be an illness almost nobody has heard of. It's an inflammatory disorder called Muckle-Wells syndrome in which a single genetic mutation results in the buildup of proteins that can cause rashes, joint pain, and fatal kidney damage. Muckle-Wells afflicts just a few thousand people worldwide, too small a number to attract most drugmakers. But Fishman and Vasella have a hunch the drug they've developed for it will prove effective in more widespread diseases. "With other companies, rare diseases are an afterthought," says Fishman. "For us they are often the starting point."
The drug, a synthetic antibody that can tamp down out-of-control immune responses, isn't new. Novartis briefly tested it against arthritis, then abandoned it. In 2004 one of Fishman's scientists asked to retest it in a trial involving just four patients suffering from Muckle-Wells. Within 24 hours of receiving the medicine, all four showed dramatic improvement, and within a week the disease was barely detectable in the blood. Patients remained in remission for as long as six months.
Despite these promising results, development efforts soon bogged down in debates over what the drug's exact commercial value might be. "This is precisely what paralyzes the industry and leads to the destruction of innovation," says Trevor Mundel, a physician-cum-mathematician brought in by Fishman as head of global development. The confusion persisted for a year and a half, Vasella recalls with irritation. The initial tests "took way too long, much longer than necessary."
Vasella ultimately resolved the disputes, and Novartis went on to test its drug in several rare autoimmune ailments. Using advanced computer models to show how different patients might respond to the treatment, Novartis was able to persuade the Food & Drug Administration that it was safe to move directly to late-stage trials involving hundreds of patients with Muckle-Wells and a related cluster of immune system diseases, thus shaving a year off the expected development time and saving tens of millions of dollars. While Pfizer, GlaxoSmithKline (GSK), and others are also using simulation, "Novartis is far ahead of the rest of the industry," says Dr. Howard Lee, director of the Center for Drug Development Science in Washington.
Vasella places a high premium on medical experience. After a major restructuring in 2007 that led to the loss of 1,260 sales and marketing jobs, Vasella replaced some of the company's senior leaders with medically trained scientists who grasped his approach. According to Shannon, some of the old guard fled voluntarily. "They saw Daniel rewarding projects such as Muckle-Wells and said: 'If this is what the future of the company looks like, it's not for us,' " he explains.
On June 3, The New England Journal of Medicine published important data on Novartis' phase 3 trial of the Muckle-Wells drug, now called Ilaris. More than 90% of children and adults suffering from the immune disorders the drug was designed to treat had rapid and sustained remissions. The drug is under priority review with the FDA, and Novartis hopes to seek approval for use against a variety of autoimmune diseases, including Type 2 diabetes and severe arthritis.
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