Personalized Approach to Cancer
A small biotechnology company focused on cancer vaccines is awaiting the results of a crucial test that could hasten an era of personalized medicine.
Much is riding on the outcome for Genitope Corp. of Redwood City, Calif., which has been toiling to commercialize a vaccine invented at Stanford University in the late 1980s.
After raising $116 million in stock sales last year, Genitope has 12 to 18 months of cash remaining. Its vaccine, aimed at an incurable form of non-Hodgkin’s lymphoma, is one of two drugs the company is developing. The company’s share price, which has ranged from $8.13 to $17.60 over the last year, closed Friday at $12.44.
More than 200 patients have been given MyVax, the vaccine produced by Genitope. What each patient received was not mass-produced, but customized to attack his or her specific tumor.
Genitope’s test will show whether its vaccine can prolong remissions in patients. A small study completed four years ago was encouraging, and although the latest trial of 300 patients was not scheduled to end until 2007, the company believes that it could see results -- and get the vaccine to market -- sooner.
The founder of Genitope is 51-year-old Dan W. Denney Jr., a scientist-turned-businessman who invented an efficient way to produce many small batches of vaccine.
All biotechnology drugs are made by splicing bits of DNA into live cells, usually rodent cells. The process turns cells into mini-factories producing a specific drug. But it can take up to a year to choose the most productive cells, and patients with cancer can’t wait that long.
Denney’s invention, which he devised while he was a postdoctoral student at Stanford, is a process that allows Genitope to quickly identify cells that would make the best drug factories. The company’s goal is to make each patient’s vaccine within six months.
Unlike vaccines for other illnesses, cancer vaccines attempt to stop a disease that has already taken hold of a patient. More than 65 of them are in development, but none has reached the market. A long list of companies -- including Avax Technologies Inc., Biomira Inc., Corixa Corp. and Progenics Pharmaceuticals Inc. -- have seen their vaccines stumble in late-stage trials.
Unlike MyVax, most cancer vaccines in development are not custom-made for patients. Typical is a melanoma vaccine being tested by CancerVax Corp. of Carlsbad, Calif., that contains 30 different fragments commonly present in skin cancer.
But personalized vaccines, although more difficult to produce, have the greatest likelihood of success, based on early test results, said Fleur Pijpers, an analyst with market research firm Datamonitor.
Scientists believe that lymphoma is particularly suited to a personalized approach because it has substances on the surfaces of tumor cells that vary from patient to patient. A vaccine made from these so-called surface antigens could train a patient’s immune system to recognize and fight the cancer, according to this theory.
Genitope’s vaccine is similar to one developed by Stanford University scientist Ronald Levy, an authority on lymphoma. Levy and his students have administered his vaccine to hundreds of patients over the years, and some patients have experienced long remissions. Levy nudged Denney, whom he had known at Stanford, to launch Genitope, and led the company’s clinical trials.
Genitope isn’t the only company working on personalized cancer vaccines; nor is it the only one that can trace its roots to Levy’s Stanford lab.
Minneapolis-based Biovest is trying to commercialize a vaccine developed by one of Levy’s former students, Larry W. Kwak of the M.D. Anderson Cancer Center in Houston. Favrille Inc. of San Diego has enlisted Levy’s assistance with its clinical trials. A fourth company, Large Scale Biology Corp. of Vacaville, Calif., withdrew from the race in a belt-tightening move.
Denney said he wasn’t worried about the competition, which he attributed to Levy’s passion about curing lymphoma one day.
“This is what I like about Dr. Levy,” Denney said. “His ultimate goal is putting patients in lifelong remission.”
Non-Hodgkin’s lymphoma strikes about 55,000 new patients in the U.S. each year. The disease begins in the lymphatic system and produces cancerous white blood cells, which invade other organs. About half of those patients have a slow moving but inevitably fatal form of the disease -- the type targeted by Genitope’s vaccine.
Chemotherapy can extend a patient’s life expectancy by five to eight years.
Clarence Mellinger, a medical technician from Boise, Idaho, became Genitope’s first patient in June 1999. By then, surgery and chemotherapy had put his disease into remission.
To Mellinger, now 59, the experimental vaccine offered a chance to avoid the inevitable cycle of harsh chemotherapy treatments, followed by shorter and shorter disease remissions. Mellinger, still cancer-free, toured Genitope’s facility in an industrial park during a visit to the Bay Area not long ago. His voice grew shaky when he recalled meeting the technician who prepared his vaccine.
“I say a prayer for him and his family every night,” Mellinger said.
Genitope says each patient receives seven shots spread over six months, along with other injections to boost the immune system. Genitope can make vaccines for 30 patients every month, a number that will go up to 300 after an expansion that is underway, the company says.
In keeping with standard practice, Genitope provided its vaccine for free to patients in clinical trials. It is unclear how much the vaccine eventually will cost. Denney says the price will be comparable to that of a full year of traditional therapy, which can range from $50,000 to $100,000. The vaccines would be cost-effective if the shots allow patients to avoid relapses and years of expensive medical care, Denney says.
Still, MyVax is not a magic bullet to end the war on cancer. Just half of all patients who receive Genitope’s vaccine consequently produce anti-cancer antibodies. And although many patients in that group experience long remissions, some do not. Denney said Genitope is studying subtle differences in tumors that may explain how patients respond.
Denney launched Genitope in 1996, and his timing couldn’t have been worse. The dot-com bubble hadn’t yet burst and investors were stampeding into Internet stocks. Denney recalled one venture capitalist complaining that Genitope “lacked an e-commerce bent.”
With advice from his brother, an accountant and a member of Genitope’s board, Denney raised $1 million to get the company going. But money wasn’t the only hurdle.
Before Genitope could begin testing its shots, the company had to assure the FDA that its vaccines wouldn’t attack healthy cells. In addition, the company had to develop a test measuring the potency of each individualized batch of vaccine.
Levy said the obstacles frequently looked insurmountable, and he often told Denney so. In fact, Levy said he warned Denney it was too early for results from the clinical trial. But he added, “Dan Denney always surprised me.”
