Washington Editor

Praecis Pharmaceuticals Inc. said the FDA accepted for review its resubmitted new drug application for Plenaxis in a defined subpopulation of advanced prostate cancer patients for whom existing hormonal therapies may not be appropriate.

The company said Plenaxis, or abarelix for injectable suspension, could provide a therapeutic alternative for those patients who may otherwise face the prospect of permanent surgical castration. Under the Prescription Drug User Fee Act, the FDA is required by law to take action on the Plenaxis application by Aug. 27.

Like many drugs and biologics that eventually make it to market, Plenaxis is no stranger to the FDA. Once the subject of a joint development and commercialization agreement between Praecis, of Waltham, Mass., and Thousand Oaks, Calif.-based Amgen Inc., the original NDA for Plenaxis in a broad patient population failed to win FDA approval in June 2001.

Subsequently, Amgen dropped the project. (See BioWorld Today, June 13, 2001, and Sept. 20, 2001.)

Now, on its own, and not looking for another U.S. partner, Praecis resubmitted its application in late February. But for the time being, the company has narrowed the population it seeks approval to treat.

"In negotiations with the FDA, they had the rich trial data from 1,500 patients in hand [previously submitted pivotal trials], and it was decided that in this particular patient population, there was an unmet medical need," Bill Heiden, Praecis' president, told BioWorld Today. "The patients have no other medicinal alternative so we decided this would be the path for registration."

Plenaxis, a gonadotropin-releasing hormone (GnRH) antagonist, can be administered in a one-month sustained-release formulation. According to the company, in Phase III trials, Plenaxis demonstrated the ability to rapidly reduce testosterone levels while completely avoiding the initial testosterone surge characteristic of LHRH, or leutinizing hormone-releasing hormone, agonists.

The resubmitted application highlights a 72-patient study of men with advanced, symptomatic prostate cancer.

"The trial was conducted at the centers where the other trials were ongoing. There were physicians who felt uncomfortable randomizing to LHRH agonists because these patients were late-stage symptomatic patients, and giving them agonists would exacerbate the symptoms and make things worse, so we created this trial idea," he said. "And as you can see, we hit all of our endpoints."

Indeed, according to a prepared statement released by the company, 100 percent of the patients met the primary endpoint, which was the avoidance of surgical castration at four to 12 weeks, and no patient required surgical castration during the follow-up phase of the study, which had a median duration of 40 weeks.

Furthermore, the study had several secondary endpoints, which evaluated improvement in various symptoms associated with the advanced prostate cancer. The company said overall, 90 percent of the patients studied experienced improvement of one or more of the symptoms associated with advanced prostate cancer.

From a safety standpoint, the company said Plenaxis was well-tolerated.

However, in the original NDA submitted, Heiden said the FDA was concerned about some incidents of severe allergic reactions. "There were three per 10,000 injections and the FDA locked onto that as a safety issue and wanted more information on it. In Europe, the regulators said that's not an issue because urologists are used to seeing that."

And on to Europe, Praecis hopes to file for approval sometime during the second quarter. Kevin McLaughlin, Praecis' chief financial officer, told BioWorld Today he expects European approval on the larger, expanded population in 12 to 14 months. Praecis will seek a partner overseas.

In the U.S., Heiden said Praecis intends to work toward seeking approval on the expanded label once it wins approval in the subpopulation.

Praecis used its LEAP (Ligand Evolution to Active Pharmaceuticals) in the development of Plenaxis, which is also being studied in endometriosis.

Last August, Praecis concluded an agreement whereby it will pay Amgen $13 million in a final settlement of all amounts payable under their terminated collaboration, initially signed in March 1999 and valued at up to $100 million. (See BioWorld Today, March 10, 1999; Sept. 20, 2001; and June 12, 2001.)

Praecis' stock (NASDAQ:PRCS) closed Wednesday at $3.97, down 13 cents.