West Coast Editor

Praecis Pharmaceuticals Inc., in the process of overcoming an FDA snag in its bid for Plenaxis as a prostate cancer treatment, revealed positive early data with the gonadotropin-releasing hormone agonist in a Phase II/III endometriosis study.

Waltham, Mass.-based Praecis on Friday will offer preliminary results from the trial in 363 premenopausal women with confirmed, moderate to severe endometriosis at the annual meeting of The Endocrine Society in San Francisco. Complete results will come later, said Kevin McLaughlin, chief financial officer for Praecis.

"We're analyzing the bone data, and I don't know what the date will be [when fully analyzed] at this point," he said.

The study compared subcutaneous doses of 30 mg, 60 mg and 120 mg to the standard dose of market leader Lupron Depot (leuprolide, an approved drug by Abbott Park Laboratories Inc., of Abbott Park, Ill.), which is 3.75 mg, given intramuscularly. Patients were treated once every four weeks for 24 weeks - a total of six doses - and were followed for 48 weeks after the course of treatment.

In endometriosis, the endometrial tissue grows beyond the uterine lining, causing a variety of symptoms, including pain, fatigue, heavy menstrual bleeding, painful sexual intercourse and infertility.

The trial's primary endpoint included three elements at four and 24 weeks: improvement of pelvic pain; improvement in pelvic tenderness; and elimination of dysmenorrhea, or difficult and painful menstruation.

The number of patients treated with Plenaxis (abarelix) at any dose who found relief from endometriosis-associated pain was no different than with Lupron Depot at four weeks. At 24 weeks, however, only those patients treated with a 60-mg dose of Plenaxis experienced statistically equivalent relief of endometriosis-associated pain, compared to patients treated with Lupron Depot. And more patients eliminated their dysmenorrhea at four weeks with all doses of Plenaxis.

Specifically, 95.7 percent got menstrual relief at the 30-mg dose, the same percentage at the 60-mg dose, and 96.7 percent at the 120-mg dose. Of the patients on Lupron Depot, 71.6 percent achieved relief.

Estrogen levels went down in patients on Plenaxis more rapidly than those on Lupron Depot, too.

As for side effects, the most common adverse reaction was headache, and no treatment-related serious adverse events or systemic allergic reactions were reported in any group. Patients treated with Plenaxis experienced more bone mineral density loss than those treated with Lupron Depot, and the loss apparently was dose related, as with other therapies that lower estrogen. Praecis is looking at the data to clarify the extent and magnitude of the bone loss.

Praecis also has submitted a protocol to the FDA for a pharmacokinetic study that would evaluate the use of a less-frequent dosing regimen for Plenaxis, with an aim to lessen bone loss by reducing drug exposure.

If the FDA goes along with the protocol, "we'll do a pharmacokinetic study during the second half of this year, and then we'll have to do additional trials beyond that," McLaughlin told BioWorld Today.

Current treatments for endometriosis include pain management medications, birth control pills and hormonal therapies. The therapies suppress estrogen production but cause an initial estrogen surge, which can worsen pain, cramping and excessive bleeding in endometriosis patients, as well as boost the risk of a tumor flare in breast cancer and the development of ovarian cysts.

"There is no surge with Plenaxis," McLaughlin noted. "The mechanism of action is very different from the other agonists that are out there."

Late last year, the agency opened the door for Praecis to pursue Plenaxis for hormonally responsive advanced prostate cancer. The company said it might submit data seeking approval by the end of 2002. Earlier in the year, Thousand Oaks, Calif.-based Amgen Inc. ended its joint development and commercialization agreement with Praecis. (See BioWorld Today, Sept. 20, 2001, and Dec. 4, 2001.)

"There are no partners for any indications now," McLaughlin said, adding that the prostate cancer indication is "still very much ahead."

The company filed its new drug application for Plenaxis against prostate cancer in December 2000, "and we heard back that we have to do a little more work," he said, which led to Amgen ending the partnership.

"We're conducting a trial where we're treating [prostate cancer patients] with three months of Plenaxis and then switching them over to an approved agonist for two months," he said. "We're accruing it right now."

The next step has not been decided. "We continue to discuss the path forward," McLaughlin said.

As for market size, he said, "prostate cancer is the much larger market, but we believe endometriosis is very much underserved." Worldwide, the market for hormonal therapy against prostate cancer is $2 billion annually, he said.

Praecis' stock (NASDAQ:PRCS) closed Wednesday at $3.15, up 9 cents.