Drug CEO's Business Becomes Personal

(Reduced from the original LA Times article) As his staff raced to test a cancer medicine that might save his life, an executive negotiated a merger that could have halted the experiments.

Michael Crockett rushed through the door at the Sunnyvale, Calif., laboratory of Scios Inc. toting an Igloo cooler. Packed inside, beneath a layer of ice, was a vial of human bone marrow. The marrow was needed to test a tantalizing hypothesis: that Scios' experimental rheumatoid arthritis pill, SCIO-469, might also treat cancer. As Crockett, manager of the company's drug projects, delivered the bone marrow to Scios researchers in February 2003, he knew there was more at stake than product development. His boss, Scios Chief Executive Richard B. Brewer, donated the marrow. Brewer had multiple myeloma.

But scientists had to work fast. The firm's board of directors was preparing to sell the unprofitable biotech to drug giant Johnson & Johnson. And there were no guarantees that the SCIO-469 cancer project would continue under new ownership. J&J saw enormous potential in SCIO-469 — perhaps a billion dollars a year — but as a pill for rheumatoid arthritis. Brewer hoped to persuade his new bosses to also test the pill in cancer patients. "I'm hoping [other patients] won't have to go through what I went through," Brewer said.

Those at Scios who had watched Brewer battle his illness believed they were on a mission. "When someone you know and respect gets a disease, you get angry," said Scios' top scientist, George F. Schreiner. "We hated myeloma…. We wanted to tear it down, plow it under the ground and put enough salt in so it never comes back."

A top priority at Scios was developing a drug to neutralize p38, an enzyme believed to spur inflammation in rheumatoid arthritis patients. Using sophisticated computer programs, Scios researchers designed molecules that looked like they might block the activity of p38, and neutralize it. Guided by the computer models, chemists then mixed one compound after another in search of a usable drug. By the end of 2000, Scios was ready to test its pill in patients with rheumatoid arthritis.

Meanwhile, Brewer faced his own struggle. The first sign of trouble came in May 2000, when Brewer felt a twinge in his back. At first, he thought he had strained a muscle when he loaded his dog, a 70-pound boxer, into the back of his SUV. But the pain worsened, so Brewer went to a doctor, who told him he had a compressed disk. His condition didn't improve with rest. By spring 2001, Brewer could not stand upright and had to sleep in a chair to avoid intense pain.

Brewer kept up a grueling schedule, which was also taking its toll. Brewer steadily lost weight and the pain got worse, despite visits to a chiropractor. Aspirin didn't help. Damage to his spine had shaved an inch off his 6-foot 4-inch height. The scientists on Scios' executive team were alarmed by their boss' worsening condition. Chief Medical Officer Darlene Horton, a physician, feared she was watching Brewer die. She warned him that he might have cancer.

"This is not normal back pain," Horton recalled telling him. "You don't need massages, you don't need a chiropractor. You need an MRI — now." But Brewer told her his bone scans, another sort of imaging test, showed no sign of disease. Finally, at the recommendation of his doctor, Brewer had a surgeon inject plastic into his spine to cushion the damaged disk. During the procedure, the surgeon took a bone marrow biopsy.

The executive learned he had myeloma, a cancer he had never heard of. In late summer 2001, Brewer started high doses of chemotherapy at City of Hope National Medical Center in Duarte. Six months later, he underwent a risky bone marrow transplant to restore damaged tissue. "It was the worst experience I could have imagined," he said. "Every cell in your body has been turned upside down and backwards. It changes you."

Brewer was back at work in April 2002. His cancer was in remission, but because myeloma is incurable, Brewer did not know how long he would remain cancer-free. His doctor at City of Hope, Stephen Forman, said remissions could last more than five years, or as little as one.

By mid-December, two firms, including Johnson & Johnson, said they wanted to buy Scios. With Scios' permission, the suitors started reviewing confidential documents in preparation for a bid. Then, in January 2003, Brewer spotted an article in a newsletter about a study that linked the p38 enzyme — the target of SCIO-469 — to myeloma. The researcher was Kenneth Anderson of the Dana-Farber Cancer Institute in Boston, an authority on the disease.

Brewer contacted Anderson, who was surprised by the call. He was used to hearing from industry scientists but seldom talked shop with CEOs. He explained to Brewer that p38 releases chemicals that spur the growth of cancerous myeloma cells. In theory, if a drug blocks p38, the tumor can't survive. Brewer turned the article over to one of his top researchers, Linda Higgins, and asked her to dig deeper. After a week of intense research, Higgins told her boss: "I think we have a shot."

Higgins needed healthy cells from human bone marrow for her experiments, so Brewer volunteered. The first anniversary of Brewer's bone marrow transplant was approaching, and he was scheduled for a full day of medical tests at City of Hope. The CEO arranged to have marrow taken for Scios at the hospital.

Higgins isolated very specific cells, called stromal cells, from Brewer's tissue. In healthy people, stromal cells form the scaffolding that supports the blood-forming cells in the marrow. In patients with myeloma, stromal cells become "brainwashed" by cancerous plasma cells to produce nourishing chemicals, called cytokines. While stromal cells do the bidding of cancer cells, they remain healthy and don't become malignant.

Four days after his trip to City of Hope, Brewer voted with the rest of Scios' directors to accept a $2.4-billion offer for the company from J&J. Brewer had not wanted to sell the company. Scios, after a decade of disappointment, had finally tasted success. Its heart drug had been approved, and the company appeared close to potential breakthroughs in arthritis and cancer. But as a director accountable to shareholders, Brewer said he could not turn down J&J's offer.

During negotiations with J&J, Brewer made a case for continuing the myeloma project after the merger. To J&J pharmaceutical group president Joseph Scodari, the research sounded plausible, but sketchy. "It was obvious to us that Dick not only saw this as a business opportunity but had a great personal interest in this," he recalled. Brewer knew the transition to new ownership would take several months, time Scios could use to build a case for the drug. "We decided to go full blast," Brewer said.

One of his first steps was to recruit expert advisors, including Anderson of the Dana-Farber institute. Anderson flew to California in late February and came away impressed with the small company's science and inspired by its CEO. “The circumstances that brought us together were very rare," Anderson said. "One has to believe there must be a reason."

Still, many at Scios worried about scientists at the company losing objectivity on a project so dear to them — and their CEO. So the myeloma team held open forums, allowing other scientists to grill them. Brewer resolved to stay out of his scientists' way.

Higgins wrote a detailed plan to test SCIO-469. She coaxed the healthy stromal cells from Brewer's marrow to secrete the chemicals that fed tumors. Then she added SCIO-469 to the mix. With a team of junior scientists, Higgins repeated each step three times with the same encouraging result: The flow of nourishing chemicals slowed. Much work remained before the pill would be ready to test in cancer patients.

By mid-June 2003, Higgins completed her work. Thirty people — Scios scientists, their academic advisors and representatives of J&J — gathered to review all the data. Higgins told the group that myeloma cells in a lab dish became weaker when SCIO-469 was added. The healthy stromal cells were unharmed.

Higgins' work suggested that long-term use of SCIO-469 would lead to the death of myeloma cells. At the very least, the experts believed, the pill would spare patients the severe bone pain and damage that Brewer had experienced. By the end of the meeting, the experts had devised a plan for testing SCIO-469 in cancer patients. "That is when our p38 inhibitor became a full development oncology project," Crockett said.

Several dozen cancer patients have taken SCIO-469 as part of a clinical trial, scheduled to end by early summer. They took the pill alone for a while, then in combination with a cancer drug called Velcade, which J&J shares the rights to market. If the results are promising, Scios plans a bigger test with more patients.

Today, three years after his bone marrow transplant, Brewer remains in remission. Brewer is not in the clear, however, and his treatments haven't ended: He receives regular infusions of a drug to rebuild his bones.

"What I am hoping is that patients will be able to take two pills a day and live with their cancer," he said. "That would be Valhalla for us."

Copyright 2005 Los Angeles Times

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