By Randall Osborne
Avax Technologies Inc. has begun a Phase III trial to prove the superiority of its M-Vax vaccine to high-dose alpha interferon, the only FDA-approved therapy for Stage III melanoma.
Avax, of Kansas City, Mo., in 1989 began conducting Phase I/II trials of M-Vax in 62 patients whose melanoma, a malignant skin cancer, had reached Stage III, which means it has spread to a single lymph node area. After standard surgical removal of the tumors, patients were treated with the vaccine on a weekly or monthly schedule.
Those trials, at Thomas Jefferson University (TJU), in Philadelphia, showed 36 of 62 patients, or almost 60 percent, still alive after a median follow-up time of 55 months. The five-year historical survival rate for Stage III melanoma, with surgery only, is about 20 percent.
Of 15 patients whose cancer had spread to two lymph node areas, five were alive after a median follow-up time of 73 months.
"The data are very robust," said Jeffrey Jonas, president and CEO of Avax.
Patients in the Phase I/II trials ranged in age from 26 to 79 years old. Older patients had abetter survival rate than younger ones. The projected five-year survival rate of patients over 50 was 71 percent, as opposed to 47 percent for those under 50.
"The findings hold up to multi-varied analysis," Jonas said. "I'm not sure I understand the mechanism, but we think it's very exciting. These are people who have difficulty tolerating chemotherapy."
In the Phase III study, measured outcomes will be disease progression and overall survival, comparing patients randomized to treatment with M-Vax to those randomized with alpha interferon. The study will involve 250 subjects at 10 to 15 sites. Its primary endpoints are projected relapse-free survival and five-year survival.
Jonas said he chose to compare M-Vax with alpha interferon because "trials that show superiority are easier to execute and they make it easier for a drug to be approved. Also, and very importantly, you have to create a marketing platform for your product. We're trying to build a company."
Avax, with six full-time employees, went public in late 1996, following a private placement in June that netted $22.5 million.
The Phase III study on M-Vax should be completed by the end of 1999, and Avax hopes to file a new drug application with the FDA by the year 2000 or 2001.
Melanoma is one of the deadlier and faster-increasing cancers. Since 1973, melanoma has jumped about 4 percent each year, from 5.7 per 100,000 in 1973 to 12.2 per 100,000 in 1993, says the American Cancer Society. In 1997, about 40,300 people will be diagnosed with the disease, and 7,300 people will die from it. A major risk factor in melanoma is believed to be overexposure to ultraviolet radiation, especially in fair-skinned people.
Avax, incorporated in 1990 as Nehoc Inc., changed its name to Avax in 1996. In 1995, the company bought from TJU the exclusive worldwide rights to develop, manufacture and sell a patented autologous cell vaccine, which works by conjugating the patient's tumor cells to a small molecule known as a hapten (dinitro phenyl) and then injecting them back into the patient along with an agent that boosts immune response (cyclophosphamide, commonly used in chemotherapy).
"Haptenized" molecules, recognized by the immune system, sometimes elicit an immune response against the unmodified cancer molecule as well.
"The science behind it is strong," Jonas said. "You avoid having to guess what are the tumor antigens that you have to target in your vaccine. It's translatable across various cancers, which is one of the advantages of this platform."
Five-Year Survival Rate 60 Percent
More than 300 human subjects have been tested since 1989 with the M-Vax autologous cell vaccine, Avax's lead product, and the patients' five-year survival rate has been about 60 percent. David Berd, a clinical oncologist at TJU, invented the technology and is chairman of Avax's scientific board.
Jonas said melanoma was chosen as the first disease target, but other cancers are being studied.
"The zeitgeist has been that, of all the tumors, melanoma is the one most likely to be responsive to immune manipulation because, although it rarely does so, it will sometimes spontaneously regress," he said.
Jonas expects other tumors to be just as responsive. "The take-home message is that a lot of people are in melanoma [research] because they believe immunotherapy is an important area to be in, and that's a good sign," he said.
A vaccine by Avax for ovarian cancer, O-Vax, has entered a Phase I/II trial, with 10 patients enrolled so far. Phase III trials may begin next year. A vaccine to treat colorectal cancer also is expected to begin Phase II clinical trials by the end of this year. Phase III trials could begin as early as 1999, Jonas said.
Avax also has acquired patent rights for two cancer therapies that are in the preclinical stage and have not been tested on humans. The company is providing research funds to the universities from which those compounds are licensed. At Rutgers University, in New Brunswick, N.J., research is being conducted on topoisomerase inhibitors, which also have shown activity against fungal and parasitic organisms. At Texas A & M University, of College Station, Texas, anti-estrogens are being tested against solid tumors.
As of June 30, Avax had $17.8 million in cash, with a net loss of $2 million for the first six months of 1997. The company's stock (NASDAQ:AVXT) closed Thursday at $4.188, unchanged. *