Progenics Pharmaceutical Inc. said Monday it started the first PhaseIII trial of a cancer vaccine based on a defined tumor antigen.

The Tarrytown, N.Y., company said enrollment began in an 800-patient study of GMK in melanoma patients who have had theircancer surgically removed but are at a high risk of relapse. TheNational Cancer Institute (NCI) is sponsoring the trial.

GMK, the lead candidate from Progenics' ganglioside conjugatevaccines, incorporates the GM2 ganglioside, which is present onabout 95 percent of melanoma cells. Gangliosides are molecules oncell surfaces composed of carbohydrates and lipids. The GMKvaccine is designed to induce antibodies against GM2.

Earlier studies of the vaccine showed patients who developedantibodies against GM2 developed statistically significant disease-free and overall survival. All patients receiving a new formulation ofthe vaccine, incorporating the QS-21 adjuvant, developed GM2antibodies, said Paul Maddon, president and CEO of Progenics.

The pivotal study will compare GMK with high-dose alphainterferon, which was approved last December for treating thesepatients. The primary endpoint is prevention of melanomarecurrence.

Maddon said the GMK would offer significant advantages to high-dose alpha interferon in terms of reduced toxicity, in addition to thehoped-for benefits of survival and quality of life. He said enrollmentis expected to take up to two years and patients will be followedabout two years.

Interim analyses scheduled during the trial could result in an earlyfiling if warranted by results, Maddon said.

Cancer centers in the NCI's Eastern Cooperative Oncology Groupand the Southwest Oncology Group will participate in the trial, aswell as the University of Texas M.D. Anderson Cancer Center inHouston and Memorial Sloan-Kettering Cancer Center in New York.

The vaccine was developed at Sloan-Kettering and licensedexclusively to Progenics last year. (See BioWorld Today, Dec. 18,1995, p. 2.) The therapeutic vaccine contains GM2 coupled to thecarrier protein keyhole limpet hemocyanin and mixed with QS-21.

That formulation has advantages over an earlier vaccine (GM2/BCG)that used BCG as an adjuvant. That formulation produced antibodiesin 85 percent of patients rather than the 100 percent generated byGMK, Maddon said, adding that antibody titers are higher in the newformulation and tolerability is improved.

Maddon said the beginning of the trial is a "significant milestone incancer research" because it's the first pivotal trial of a cancer vaccinebased on a defined tumor antigen. "It's considered to be a ground-breaking study." (Ribi ImmunoChem Research Inc., of Hamilton,Mont., already is in Phase III with its Melacine melanoma theraccinefor melanoma, but that uses tumor cells lysed and killed to act as anantigen.)

Having a product in Phase III also is significant to Progenics in that itsets the company apart from so many other biotechnology companiesthat are in much earlier stages of development or research, Maddonsaid.

Privately held Progenics raised $7 million in April 1996 through aprivate placement of convertible preferred stock. The company plansto do an initial public offering but that move is not imminent now,Maddon said.

Progenics plans to have five products in the clinic this year, inaddition to a second Phase III trial of GMK in Europe and Australia.One product expected to start clinical trials, MGV, is anotherganglioside conjugate vaccine being developed for cancer. The HIVimaging agent ProScan-A already is in the clinic and a different doseof the radiolabeled antibody, PRO 367, is expected to start trials.Another product expected to go into the clinic this year is the nakedantibody PRO 542 for HIV.

Maddon said Progenics could add additional products to its pipelinethis year, both in the cancer and virology areas. He said corporatepartnerships also are possible in the near term. n

-- Jim Shrine

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