By Debbie Strickland

A vaccine to stimulate the body's own immune cells to act as roving bloodstream assassins against cancer has long been a holy grail in pharmaceutical research, and now a small Tarrytown, N.Y., company has what could be the first successful vaccine for certain stages of malignant melanoma in Phase III.

Progenics Pharmaceuticals Inc.'s GMK cancer therapy caught the attention of big pharma player Bristol-Myers Squibb Co., of Princeton, N.J., which has agreed to support clinical development and marketing, and pay up-front and milestone fees, as well as royalties on any eventual sales. Financial terms were not disclosed.

"This could be described as the major event in the history of our company," said Paul Maddon, Progenics' chairman and CEO.

The worldwide licensing agreement, which also covers a second, earlier-stage cancer vaccine, gives Bristol-Myers Squibb, maker of the chemotherapeutic Taxol (paclitaxel), its first potential vaccine-based cancer treatment.

"This is the only cancer vaccine at this time that has provided this type of proof of principle in the setting of a randomized trial in human patients," said Dr. Renzo Canetta, vice president for antitumor clinical research and development at the Bristol-Myers Squibb Pharmaceutical Research Institute, in Wallingford, Conn.

He emphasized, however, that the treatment has shown efficacy in patients with surgically resected melanoma and is not a cure for metastatic disease.

Although privately held Progenics declined to release current financial data, the company had $1.75 million in cash when it filed for an initial public offering (later withdrawn) last fall. The 30-employee company, however, progressed to late-stage clinical trials by winning government sponsorship of Phase III studies of the melanoma vaccine in the U.S. and Europe.

Vaccine In Phase III Testing

GMK is currently in a National Cancer Institute-sponsored pivotal Phase III clinical trial for patients with Stage III melanoma that involves several cancer research groups in the U.S. and Canada. Enrollment of 850 patients is expected to be complete by the end of 1998.

A second pivotal Phase III trial, also for Stage III melanoma patients, will be initiated later this year in Europe, Australia and New Zealand. In addition, the European Organization for the Research and Treatment of Cancer will be conducting a Phase III study in patients with Stage II melanoma.

"Our primary endpoint in Phase III is disease-free survival," said Maddon.

Progenics' cancer vaccines are designed to stimulate a patient's immune system to control or eradicate residual cancer cells following surgical removal of surface melanoma. GMK incorporates the GM2 ganglioside, a cancer antigen present in approximately 95 percent of melanoma cells.

The gangliosides, molecules with carbohydrate and lipid components, are attached to immunogenic carrier proteins to create a conjugate vaccine, which when combined with an adjuvant, unleashes a specific antibody attack on cancer cells.

"Our vaccine is based on a defined cancer antigen," Maddon told BioWorld Today, when asked what distinguished GMK from other experimental cancer vaccines, such as Melacine, which is under development by Ribi ImmunoChem Research Inc., of Hamilton, Mont.

Melacine is a whole-cell vaccine that has demonstrated improved quality of life in Phase III studies for Stage IV (metastatic) melanoma. The vaccine is composed of lysed cancer cells combined with an immune system-stimulating adjuvant.

Phase II GMK Data Positive With No Side Effects

Progenics reported Phase II studies have shown vaccination of melanoma patients with GMK vaccine resulted in the formation of antibodies against GM2, which killed melanoma cells with no significant side effects to the patient. Patients with Stage III melanoma who have developed antibodies against GM2 remained disease free for significantly longer periods and had longer overall survival.

Improved quality of life is a bonus to vaccine therapies compared to traditional chemotherapies and radiation techniques, Maddon said.

As for the potential market, the company notes melanoma will strike about 40,000 U.S. residents this year, a 12 percent increase from 1996, according to the American Cancer Society.

The other vaccine covered in the Bristol-Myers Squibb agreement is MGV, currently in Phase I/II trials to evaluate the safety and immunogenicity of the vaccine in melanoma patients. MGV incorporates the gangliosides GD2 and GM2, antigens found on the surface of tumor cells such as colorectal and gastric cancer, small cell lung cancer and sarcoma.

Progenics' other major research program, comprising two technologies, centers on HIV. Its universal antiviral binding agent (UnAB) technology produces antibody-like molecules designed to neutralize or destroy HIV or HIV-infected cells. A second approach, HIV Fusion (CCR-5), inhibits the entry of genetic information from the HIV virus into cells, thus preventing the initiation of viral replication.

The company expects by the end of 1997 to initiate Phase I/II trials of two prospective UnAB treatments and to announce a collaboration involving the CCR-5 program. *