By Kevin Davies
July 14, 2004 | "Stunning success," trumpets the headline of the full-page advertisement. "Deadly cancer at 23. Complete remission at 24 ... Think what's possible." Direct-to-consumer marketing may be all the rage, but few pharmas can trumpet stories like that.
Gleevec "is probably the most significant breakthrough in cancer therapy in 50 years," says Sasha Kamb, Novartis' new head of oncology. "Compared to many other therapies, it's like a vitamin — patients take it with their juice in the morning, go to work, and have no signs of disease."
In his book Magic Cancer Bullet, Novartis CEO Daniel Vasella describes the development of the tiny orange pill formerly known as Glivec. (The FDA worried that patients might confuse it with similarly named drugs, and allowed Novartis to change the name to Gleevec!) Vasella credits his company's culture, which encourages high-risk research and innovative science.
Gleevec won FDA approval in record time, but even so, it took a decade for it to reach the market. STI-571 was initially synthesized in the early 1990s by Jurg Zimmermann, who was searching for a potent inhibitor of tyrosine kinases. "Astonishingly — and we can hardly admit that today," Zimmermann confesses, "all the experiments were done on the side and were received with a certain indifference," because chronic myelogenous leukemia (CML) is such a rare disease.
RACE FOR A CURE: Daniel Vasella credits Novartis' corporate culture for its cancer blockbuster.
Lacking an atomic structure of the target protein, Zimmermann's team resorted to an iterative trial-and-error approach, maximizing selectivity without sacrificing potency or solubility. "The crazy thing," Zimmermann says, "was that even though we had [computer-assisted modeling] data, we eventually fell back on pen and paper."
Many hurdles had to be overcome, including toxicity in early animal studies, and concerns about the drug's solubility and bitterness. But Phase I trials took less than one year, as patients stunned the physicians with normal white cell counts and a "cytogenetic response" — the loss of the telltale Philadelphia chromosome marker. By Phase II enrollment in 1999, CML patients were clamoring for the drug. Once started, FDA review took less than two months.
Vasella is committed "not to become known as a one-product company." Nor is he concerned by criticism that the company is not developing fashionable — and profitable — "lifestyle" drugs. "It seems so much more important to us to be involved in researching and developing life-saving drugs."
That attitude is shared States-side. Fishman "is a strong proponent of treating disease where you can make progress, and not have the marketing forces in control," Kamb says. "If you can cure patients, even if it's a small number, it may be better than putting another NSAID on the market. In general, I think the company does understand."
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