Genentech Gearing Up for Potential Blockbuster
Inside Genentech Inc.’s South San Francisco factory, technicians in sterile garb are stockpiling what could be the next big cancer drug.
Genentech’s Avastin could receive Food and Drug Administration approval for colon cancer in a matter of weeks, industry analysts believe. It would be the first medication to arrest cancer by reducing the blood supply to tumors, a technical feat in an area that has yielded mostly failure.
Investors have added about $30 billion to Genentech’s market value since May, when the company announced that Avastin, tested in combination with a standard chemotherapy drug, had prolonged the lives of patients with colon cancer that had spread to other organs. Typically such patients can expect to live 12 to 15 months; patients in the Genentech study survived an average of 20 months.
Wall Street believes that Avastin could become a $2 billion-a-year blockbuster.
Colon cancer specialists said Avastin would change the way they treat patients with the disease, which is second only to lung cancer as a cause of cancer death. But they are cautious about hyping the drug, which does not cure cancer.
Dr. Leonard Saltz of Memorial Sloan-Kettering Cancer Center in New York said the Avastin trial had produced the best results seen in patients with metastatic colon cancer and should become a standard treatment. “But it is hardly a home run,” he said.
When William Sinai started on Avastin in April 2002, the retired Los Angeles teacher had been given than 12 months to live. Though surgeons had removed 15 inches from his diseased intestine, cancer had spread to his liver.
Sinai, 66, improved on twice-a-month infusions of Avastin and standard chemotherapy drugs. Then, in January 2003, new tumors appeared on a CT scan. His physician, Dr. Sheldon J. Davidson of Northridge Hospital Medical Center, kept Sinai on Avastin but changed his chemotherapy. Today, while Sinai’s tumors aren’t gone, the experimental regimen has stopped his cancer from spreading. Last month, he felt well enough to accompany his family on a four-day Mexican cruise. “We’re making memories,” Sinai said.
Davidson believes Avastin is working for Sinai but can’t be certain. “All my Avastin patients are doing well. But you can go somewhere else and find a different result,” said Davidson, who has six patients on the Genentech drug.
It took Genentech 15 years to produce Avastin, an undertaking many on Wall Street considered a long shot. Seven highly touted drugs from other companies had failed to block the supply of blood to tumors in clinical trials. In an earlier human test Avastin itself did not help breast cancer patients.
But Genentech Chief Executive Arthur D. Levinson, formerly the company’s research boss, believed in the drug, which evolved from a junior scientist’s research project.
His faith sprang from positive results in the second of three trials required for FDA approval. Levinson kept a binder containing the results in his office. “I looked at it every day,” he said in May.
Now Avastin is being tested in at least three other cancers and with different drug combinations. Some analysts believe success in additional trials could transform Genentech, already the world’s second-largest biotechnology company. Every $100 million in Avastin sales adds 10 cents a share to Genentech’s earnings, analysts said.
Levinson has avoided making predictions. “If the premise works, it will certainly be a big drug,” he said. “But there are a lot of ifs.”
One if, according to analysts, is whether Genentech can prove that Avastin works with oxaliplatin -- the chemotherapy drug Sinai is taking. Genentech tested Avastin with irinotecan, another standard chemotherapy drug. But oxaliplatin’s use in colon cancer has been growing since Sanofi-Synthelabo launched it in mid-2002. Mark Schoenebaum of U.S. Bancorp Piper Jaffray wrote that success with oxaliplatin was critical for Avastin to achieve $2 billion in sales.
Avastin is a synthetic antibody that blocks a protein called VEGF, for vascular endothelial growth factor. The protein plays an important role in blood vessel formation, a process called angiogenesis.
Avastin works by pruning the tangle of blood vessels that normally surround tumors, giving chemotherapy a clear path to the cancer. Avastin must be used with chemotherapy because it is not powerful enough to shrink tumors on its own.
Dr. Susan Desmond-Hellman, the Genentech executive vice president who oversees drug development, said Avastin can be added to chemotherapy without making patients feel worse. Because chemotherapy drugs kill healthy and cancerous cells, they often have serious side effects. Avastin causes high blood pressure, which can be easily controlled with medication, she said.
However, one of the 400 patients on Avastin in Genentech’s trial had a bowel tear and died from complications.
Genentech expects FDA approval by the end of March, based on the agency’s own timeline. The company, prepared to launch Avastin as soon as it is approved, is stockpiling the drug and has hired a team of seasoned sales reps to promote it.
Genentech hasn’t said what it will charge for the drug, but analysts said the medication would add $15,000 to $20,000 to each patient’s treatment tab. The company must persuade insurers that Avastin is worth the additional expense. That might be difficult because a chemotherapy regimen that included oxaliplatin appeared to work as well as an Avastin regimen in a recent clinical trial -- and would probably cost less.
Chief Operating Officer Myrtle S. Potter said Genentech, marketer of the blockbuster cancer drug Rituxan, has a strong track record in obtaining reimbursement for its products. She said Avastin’s price would reflect “the value being given to patients.” But she added: “Our No. 1 priority is to make sure patients get the drug.”
Cost pressures might ultimately lead to tests that identify patients most likely to benefit from Avastin and other new biotechnology treatments, analysts said. Fewer than half the patients who received Avastin with chemotherapy responded to the treatment, according to Genentech’s published data. Genentech’s scientists don’t yet know why.
Dr. Heinz-Josef Lenz of USC’s Keck School of Medicine suspects the answer is in patients’ genes. Lenz and other scientists have linked specific genes and resistance to colon cancer drugs 5-fluorouracil, irinotecan and oxaliplatin. In its recent trial, Genentech didn’t look for genetic links. But Lenz plans to do so as part of a federally funded Avastin trial he is conducting with colon cancer patients.
The new treatments “are exciting but they come at a certain price -- we don’t know how to use them,” Lenz said. “The challenge will be to find out which drugs in what combination work best for individual patients.”
Still, there is no question that the outlook for colon cancer patients has improved, said Dr. Mace L. Rothenberg of Vanderbilt-Ingram Cancer Center. Two decades ago few patients lived more than six months, he said. “Now we have extended life expectancy to 20 months. It is really quite remarkable.”
Cancer patient William Sinai would agree. While receiving a drug infusion at Northridge Hospital’s Leavey Cancer Center one recent morning, he said: “I think of every drop as adding a minute to my life.”
He is so grateful for Avastin that he agreed to appear on a billboard for the drug displayed on Genentech’s campus. On a visit to the company’s headquarters, he met the scientist who invented Avastin, Napoleone Ferrara.
“I gave him a big bear hug,” Sinai said.
