By Karen Pihl-Carey
Phase III data of abarelix-depot-M show the prostate cancer drug offers an advantage over current therapies by keeping testosterone levels in check. The results, presented Tuesday at the American Society of Clinical Oncology meeting in New Orleans, provide Amgen Inc. and Praecis Pharmaceuticals Inc. with information needed for a new drug application filing expected within a year.
About 85 percent of new prostate cancer tumors grow aided by testosterone. While the goal of hormonal treatment is to shut off the body's supply of testosterone, current therapies cause an initial increase in testosterone, delaying the eventual benefit and putting the patient at risk for tumor growth for up to four weeks.
Abarelix appears to shut off the testosterone supply much more quickly, according to the data.
"Abarelix is the first in a class of hormonal therapies for prostate cancer that is sort of an elegant solution to the problem that urologists have had with arresting the surge in testosterone," said David Kaye, associate director, corporate communications for Thousand Oaks, Calif.-based Amgen. "That has been a consequence of the current hormonal therapies. Urologists know that testosterone stimulates the prostate cancer tumors, and paradoxically, when you start on the currently available therapies, testosterone surges and urologists know that can't be a good thing. Abarelix is the first drug to very quickly shut down the testosterone."
Analysts Dennis Harp and Kevin Tang, of New York-based Deutsche Banc Alex. Brown, said in a research note that Amgen could file the NDA as early as the fourth quarter of this year. They estimate third-year abarelix sales could be about $300 million.
Kaye said it's too early to estimate when the drug might make it to the market, but he expects an NDA filing within a year. Worldwide, the market for hormonal therapies is thought to be about $2 billion, he said.
"We're completing some safety studies, companion safety studies, that need to be part of the NDA package. But within a year we hope to have the submission ready to go," Kaye said. "Things are moving along very well. We're pleased with the Phase III results. They're compelling results, and we hope to file shortly."
In one of two studies, abarelix-depot-M was compared with leuprolide in 271 prostate cancer patients. A total of 72 percent of the abarelix-treated patients achieved low levels of testosterone after one week of therapy, while none of the patients treated with leuprolide achieved this (p<.001). Also, 100 percent of abarelix-treated patients avoided an initial testosterone surge, compared with 18 percent of patients on Lupron (p<.001).
In a second study, researchers combined a therapy of leuprolide and bicalutamide and compared it with abarelix. "Then you have a two-drug solution," Kaye pointed out. "And here in one therapy we've got a drug that quickly shuts down production of testosterone."
In 255 patients, 68 percent of those treated with abarelix achieved lower levels of testosterone suppression after one week of therapy. None of the patients treated with the combined therapy achieved the same result (p<.001). Again, 100 percent of abarelix-treated patients were able to avoid an initial testosterone surge, compared with 14 percent of patients on the combination therapy (p<.001).
All three therapies, however, were well tolerated and achieved and maintained testosterone suppression from day 29 through day 85 in more than 90 percent of the patients.
Harp said there are three advantages abarelix-depot-M has over the current therapies.
"One is that it eliminates the surge in testosterone that is always seen with Leupron [leuprolide]," he told BioWorld Today. "That's important because prostate cancer feeds on testosterone for its growth. The cancer is made worse by existing therapies, initially. The second claim is that abarelix has a faster onset of action. Nearly all the patients achieved, basically, castrate levels of testosterone by day eight. That was not the case for patients on Leupron. The third advantage is that abarelix is suitable for high-risk patients because it eliminates the testosterone surge."
Amgen gained rights to develop and commercialize abarelix in March 1999 through a $100 million collaboration with Praecis, of Cambridge, Mass. The rights included all human indications in North America, Australia, Asia and certain other markets. Synthelabo, of Paris, has the rights to abarelix in Europe, Latin America, the Middle East and certain African countries through a $78 million deal. (See BioWorld Today, March 11, 1999, p. 1; and June 6, 1999, p. 1.)
Another formulation of abarelix - abarelix-depot-F - is being tested in Phase II/III trials in women with endometriosis.
"Similarly, endometriosis is stimulated by female hormones, and being able to arrest female hormones is a treatment for endometriosis," Kaye said.
Amgen's stock (NASDAQ:AMGN) closed Tuesday at $55.562, down $1.62. Praecis' stock (NASDAQ:PRCS) closed at $14.875, down $2.187.