When the first results from patient trials appeared on Dr. Daniel Vasella's desk in April 1999, the chairman and CEO of Novartis sensed that an important chapter of medical history was about to be rewritten. The results indicated that Gleevec, the tiny orange capsule -- the development of which he had spearheaded -- was working wonders to arrest a life-threatening form of blood cancer. Here, for the first time, Dr. Vasella recounts the step-by-step challenges of bringing this revolutionary medicine to market and producing it in large enough quantities to make a difference in the lives of patients and their families everywhere in the world. The leaders of major pharmaceutical companies rarely speak out so candidly and comprehensively about their businesses, but in this unique, groundbreaking book Dr. Vasella takes us behind the scenes and reveals the enormous pressures, the heavy costs, and the high risks involved in betting heavily on a drug like Gleevec -- regarded by many as the most exciting cancer breakthrough discovery yet -- while staying focused on the ultimate goal of saving lives. In this clear and exciting account, Dr. Vasella explains why Gleevec is nothing less than a scientific breakthrough, one that medical experts believe already is revolutionizing cancer therapy. For decades the standard way to combat cancer has been to remove it surgically and/or to use toxic drugs or radiation to destroy cancer cells. But these techniques also attack normal tissues and frequently leave patients overwhelmingly weak. Side effects can be so severe that patients even die from therapy. In contrast, Gleevec is the first "designer drug" for cancer therapy, specifically targeting a cancer-producing molecule and "fixing" the malfunction, leaving healthy cells intact. It is hoped that Gleevec will be a paradigm for other molecularly targeted drugs that will work on cancers with larger patient populations, and the implications of this are enormous. Magic Cancer Bullet is the first authoritative account of how Gleevec was developed and produced; of how on May 10, 2001 it won the swiftest passage from the Food and Drug Administration ever for a cancer drug; of how, even now, it is changing the lives and outlooks of patients everywhere, bringing hope in bleak and dire circumstances. From his unique vantage point as the man who guided this lifesaving "magic cancer bullet" from the laboratory to the pharmacy, Dr. Daniel Vasella gives us an insider's account of the scientists, the Novartis executives, and the Gleevec patients on this remarkable journey and he shows why the story of Gleevec is an intriguing part of the search for a cure to the scourge of cancer, one of the greatest human afflictions of our time.

Dr. Daniel Vasella has been the chairman and CEO of Novartis, one of the world's largest pharmaceutical companies, since it was formed in 1996.

It's in Our Genes!

Why the excitement over Gleevec?

To begin with, for so long, cancer has been the equivalent of a death sentence. While much progress has been made in combating some forms of cancer, a death sentence still hangs over many, many cancer victims.

Against this dark landscape comes Gleevec.

No other cancer drug has exhibited so much success so quickly with tolerable side effects.

And for the very first time, cancer patients - specifically, patients passing through the early stages of CML - have eliminated or at least slowed down the cancer within them by simply taking a few pills each day.

This means no injection is required, no radiation, no surgery. It also means the absence of the common side effects in chemotherapy: vomiting, profuse diarrhea, infections, and bouts of massive depression.

The capsule allows most patients to lead a normal life.

To CML patients, the news about Gleevec has seemed too good to be true. Until now, their news has all too often been dark and tragic. Some 20 to 30 percent die within two years of diagnosis; and 25 percent die each year after that.

Designer Drug

The main reason for the excitement surrounding Gleevec is its innovative approach to cancer therapy. Indeed, if Gleevec did nothing more than help CML patients combat their disease, we would have much less cause for the enthusiasm this drug has produced.

What we have in Gleevec is nothing less than a scientific breakthrough that many medical experts say will revolutionize cancer therapy. The hope is that Gleevec represents a paradigm for other molecularly targeted drugs that will work on cancers with larger patient populations.

The standard way to combat cancer has been to remove it surgically and/or use toxic drugs or radiation in order to destroy cancer cells.

These techniques also attack normal tissues and while curing some cancers, frequently leave patients overwhelmingly weak. These therapies have saved many lives, but their side effects can be so severe that patients even die from therapy. But these techniques were all that we had for many decades.

With Gleevec, the focus has shifted to a drug that specifically targets a cancer-producing molecule, in effect shutting that molecule down, and thus keeping it from inducing cancer.

Gleevec offers the proof of a new and innovative concept, using genetic information and insights on molecular pathways. It represents the first designer drug for cancer therapy, and one of the first examples of rational drug design arising from the new field of human genome studies.

Gleevec is "designed" to target only cancer cells, leaving normal, healthy cells intact. In that sense it is a great advance upon the most popular form of treatment for CML patients, interferon, a biotech drug.

To be sure, chemotherapy has helped thousands of patients. In a number of cancers, including Hodgkin's disease and some childhood leukemias, for example, over 90 percent of patients can be saved if the disease is discovered early enough.

Gleevec is the first of a new class of drugs called signal transduction inhibitors, so called because these "STIs" interfere with the pathways that signal the growth of cancerous cells. When an STI interrupts a signal transduction pathway, a cell stops dividing, halting the cancer.

With its new mechanism of action proving so successful, Gleevec has already ignited a good deal of research aiming at the development of more drugs using the same approach.

Of course, scientists had an advantage in trying to develop Gleevec: the early discovery that a genetic defect caused CML, i.e., that the disease was the outgrowth of a certain process operating via a molecular signal pathway. This encouraged scientists to seek out a specific compound that would combat the disease.

Even before scientists get around to other Gleevec-like molecularly targeted drugs, they are eagerly investigating whether the drug will work on other cancers besides CML.

Scientists have noted that Gleevec inhibits the activity of three members of a family of enzymes - so-called kinases - that has over 100 members.

One family member was Bcr-Abl, the oncogene that resulted from the formation of the Philadelphia chromosome, the main marker for CML.

The other two family members are PDGF-R (Platelet-Derived Growth Factor) and c-Kit.

We at Novartis knew about PDGF-R and Bcr-AbI when we made ST1571, but it was Dr. Brian Druker, working in his laboratory in Portland, Oregon, who showed that ST1571 also affects c-Kit.

C-Kit is involved in GIST - Gastrointestinal Stromal Tumors - a rare tumor, which occurs in some 2,000 Americans a year. A GIST tumor can only be treated by surgery and unless eradicated, the disease is usually fatal.

C-Kit may also be involved in small cell lung cancer, accounting for as many as one-third of all lung cancers.

The PDGF-R enzyme is involved in a variety of cancers.

So, hope exists that Gleevec will work in other cancers where these enzymes play a role in cancer growth. Accordingly, Novartis has started patient trials in the generally deadly glioblastoma, a very aggressive brain cancer; some forms of prostate cancer; breast cancer in combination with other drugs; small cell lung cancer; and GIST.

The fight against cancer goes on and each new, effective drug like Gleevec is a small victory in a much larger, ongoing war.

In offering a whole new approach to cancer therapy, Gleevec opens a whole new category of cancer drugs. For CML patients, the drug may mean the difference between life and death; for cancer therapy, the drug offers proof that a new, promising field exists and has validity.

The excitement surrounding Gleevec is only natural considering the unshakeable, unvarnished truth that for still too many cancer victims the disease offers little other than a death sentence - or at least, a long period of suffering.

Until radiation came along in the 1920s and chemotherapy in the 1950s, cancer patients truly faced death sentences, except the minority who had successful surgery ...

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Excerpted from Magic Cancer Bullet by Dan Vasella
Excerpted by permission. All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.