By Mary Welch
Progenics Pharmaceuticals Inc. said that an unplanned early analysis on a subset of 880 patients enrolled in its Phase III trial of GMK melanoma vaccine showed that patients receiving GMK did not do as well as the patients receiving high-dose alpha-interferon.
"We are disappointed, but I'm hopeful," said Paul Maddon, the company's chairman, CEO and founder. "This is the first-ever negative news we had to release, and I feel terrible. It was something we couldn't control. It was out of our hands."
The news hit the company's stock price hard. Progenics' stock (NASDAQ:PGNX) closed Friday at $10, down $23.06, or 70 percent.
Progenics doesn't know why the Eastern Cooperative Oncology Group (ECOG), a group of physicians overseeing the trial, conducted the early analysis. The first interim results were not scheduled until the end of the year.
"ECOG did the analysis and then told us afterwards," Maddon said. "We weren't informed of anything until it was done. It was not the normal way."
Although the trial was fully enrolled, the analysis was conducted at a time when only half of the patients had received the two years of GMK therapy called for in the study protocol and most of the interferon patients had completed their full course of therapy.
The interim results indicated that the relapse-free and overall survival rates for patients receiving the vaccine were lower than those for patients receiving high-dose alpha-interferon, an approved agent. As expected, GMK was better tolerated than alpha-interferon, with about five times less frequent and much less severe side effects, ECOG reported.
"The ECOG study was done with only a subset of patients instead of all the regular patients - those with an intent to treat," Maddon said. "But interferon works intensely in the first months of treatment and then the effects wane. With GMK, and any vaccine, it takes longer to take effect. It has long-term effects. These are very disparate therapies."
Maddon said it almost wasn't surprising that interferon showed better results. "The onset of clinical effect for a vaccine appears later than that of other cancer therapies, which are given in high doses over a much shorter period of time. From what we know, the relapse-free and overall survival rates for the GMK vaccine in the Phase III trial are tracking generally as expected at this time based on our previous clinical experience."
Progenics doesn't know the specifics of the ECOG report.
"We don't really know what happened," Maddon said. "We haven't reviewed the data. We've done no analysis. But we felt an obligation to put the news out."
Maddon said he spoke with GMK's partner, New York-based Bristol-Myers Squibb Co. "We've talked but we've not had a lot of discussion. It's early and both of us need to get the information and look at the data."
The Phase III trial has been "rolled over" to an extension study until the scheduled completion of the original trial. With that extension trial, it is essential that the "integrity of the databases and the follow-up be conducted exactly as explained in the protocol," Maddon said. "That will be done. It is also essential to make the drug available to patients and we will be doing that as well."
The next interim data will be scheduled now for late next year, he said.
The GMK vaccine is designed to stimulate a patient's immune system to control or eradicate residual cancer cells after the tumor has been resected. GMK incorporates the GM2 ganglioside, a cancer antigen found in about 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.
The Phase III study, the largest ever performed in melanoma, was conducted at 300 medical centers throughout the U.S.
Progenics' relationship with BMS dates back to 1997 when BMS agreed to support GMK's clinical development and marketing in a deal worth up to $61 million in up-front and milestone payments. The company received $13.3 million up front, and BMS gained worldwide rights to the GMK and MGV vaccines, which is a second ganglioside conjugate vaccine. 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. (See BioWorld Today, July 21, 1997, p. 1.)
Maddon said the news will result in no layoffs at the company. "We haven't even spent the money from our IPO [initial public offering] from 1997. We have $65 million in cash and a negligible burn rate."