Finally, in June 1998, with FDA permission to proceed, Druker administered STI571 to a human being, a 68-year-old Oregon man with CML. “It was almost anticlimactic,” Druker recalled, “in that we’d been ready in November 1996 and here it was over a year and a half later.”
He had recruited two eminent oncologists to help run the clinical trial, Moshe Talpaz at the M.D. Anderson Cancer Center in Houston and Charles Sawyers at UCLA. All the CML patients enrolled in the three cities had undergone interferon therapy and either had failed to improve or had relapsed. None was eligible for a bone marrow transplant.
Gradually increasing the STI571 dosage, the physicians observed by around six months that astronomical white blood counts of nearly 100,000 cells per cubic millimeter were falling to less than 10,000, well within normal. Analysis of one of the first patients’ white blood cells found no signs of the Philadelphia chromosome, suggesting the leukemia had been stopped at the source. More impressive, whatever trace of the BCR-ABL gene remained had ceased copying itself. “That’s when we knew we had something the likes of which had never been seen before in cancer therapy,” Druker said.
As word spread on the Internet, other CML patients wanted in. Druker pressed Novartis to produce more of the drug. But Novartis wasn’t ready. The drug was difficult to make, Daniel Vasella, then the Novartis chief executive officer and now chairman of the board, would recall in his book about the drug, Magic Cancer Bullet. “Nor was [the drug] a high priority, given the small number of CML patients,” he added. Plus, proving that it was both safe and effective would require a substantial investment. “A severe side effect could develop in one out of 1,000 patients and that would be the end of the trial,” he wrote.
In September 1999, Druker got an e-mail from a 33-year-old CML patient in Montreal, Suzan McNamara. She’d been on interferon, which had suppressed her disease for nearly a year, but now it was roaring back, and she wanted to join an STI571 trial. “I was sick to the point where I could barely leave my house,” she recalled to me.
Druker phoned her the next day and said it would be months before she could enroll in a study—Novartis had not committed to producing more STI571. But, he added, the company might move more quickly if it heard directly from patients.
McNamara and a friend used an Internet site to create a petition requesting that the drug be made more widely available; thousands of CML patients endorsed it. She sent it to Vasella with a letter saying, “We have viewed with growing concern our belief...that the supply of the drug has not been sufficient to expand the trials as fast as the evidence to date would warrant.”
“The letter could not be ignored,” Vasella has said. The company increased STI571 production.
The honor of announcing the early clinical results fell to Druker. In New Orleans on December 3, 1999, he told an auditorium full of hematologists that all 31 patients in the study responded favorably to STI571, with the white blood cell counts of 30 falling to normal within a month. The pill’s side effects—upset stomachs, muscle cramps—were what oncologists term “mild to moderate.” Druker says he doesn’t remember the standing ovation.
The findings were “a molecular oncologist’s dream come true,” wrote Harold Varmus, who now heads the National Cancer Institute and was awarded a Nobel Prize for research that laid some of the groundwork for STI571’s success. The drug, he recalls in his 2009 book, The Art and Politics of Science, was “the best evidence to date that the most fundamental aspects of cancer research had dramatic benefits for patients with cancer.”