Prostate cancer patients gained a new treatment option on Nov. 25 as the FDA approved Plenaxis, a drug fully developed by Praecis Pharmaceuticals Inc.
The first gonadotropin-releasing hormone antagonist available as a depot formulation, Plenaxis (abarelix for injectable suspension) is indicated for pain relief in advanced symptomatic prostate cancer patients who meet a variety of conditions. First, they are not viable candidates for treatment with luteinizing hormone-releasing hormone agonists, and they refuse surgical castration. Patients must exhibit one or more other conditions, including a risk of neurological compromise due to metastases, ureteral or bladder outlet obstruction due to local encroachment or metastatic disease, or severe bone pain from skeletal metastases persisting on narcotic analgesia.
For Waltham, Mass.-based Praecis, the approval is a company milestone.
"Most importantly, this product is totally homegrown," Praecis Chairman and CEO Malcolm Gefter told BioWorld Today. "Its concept and inception were conceived at the founding of the company, and we have executed every single aspect of the research, development, formulation, regulatory [filings], manufacturing and now sales and marketing all by ourselves. It really represents our ability to execute a fully integrated business strategy."
Praecis said it plans to begin hiring a sales force immediately, with initial product shipment targeted for early first quarter of next year. Gefter said revenue generated from the drug would push the company into profitable territory by 2006.
Praecis estimates Plenaxis is entering a U.S. market worth about $1.2 billion, and that the drug could grab 15 percent or more of that sum.
"Plenaxis is really the first new hormonal therapy for prostate cancer in the last 15 years," Marc Garnick, Praecis' executive vice president and chief medical officer, told BioWorld Today. "From the practicing physician perspective, the population for which the product is approved - with a risk-management program - is for patients who have advanced symptomatic forms of prostate cancer whose main therapeutic option is to have surgical removal of their testicles. This provides an important alternative to that population of patients, and in whom currently available therapies are not appropriate."
Such current products include luteinizing hormone-releasing hormone agonists that cause an initial surge in testosterone before lowering testosterone to desired therapeutic levels, which has been linked to an exacerbation of symptoms in some patients. Plenaxis reduces levels of testosterone with no initial surge, as evidenced by findings from two randomized, active-comparator trials in which all 348 Plenaxis patients and 28 of 172 comparator patients avoided the surge.
Use of the drug will have limits, though, beyond the aforementioned criteria. For safety reasons, Plenaxis is approved with marketing restrictions and will be available only to physicians and hospital-based pharmacists who enroll in the PLUS (Plenaxis User Safety) program. The program is designed to provide safety information for patients, as well as education and support for physicians and pharmacists.
The approval includes information on risks such as immediate-onset systemic allergic reactions, comprised of fainting as a result of lowering of blood pressure and episodes of rashes or itching. Garnick said such reactions were seen in 15 out of 1,400 patients included in the new drug application, while in a study of 81 indicated patients, three such reactions emerged.
"The FDA has felt that the allergic reaction is important from a safety perspective," he added, "and consequently wanted to make sure the product is used appropriately in the indicated population."
The safety issues came as no surprise. Earlier this year the FDA warned Praecis of a three-month decision-making delay as the agency and company worked to finalize the risk-management program. (See BioWorld Today, July 22, 2003.)
William Heiden, Praecis' president and chief operating officer, said such restrictions would not limit the drug's marketability.
"Right from the start, we knew that our label would be for the advanced symptomatic patient population," he said. "The risk-management plan just supports the use of the drug in that indicated population. Our expectations have been built around focusing on this patient population in the near term, and our financial [projections] that would take us to profitability are all based on that patient population."
The approval stems from a resubmission of a new drug application that the FDA rejected two years ago. The original submission was based on use of the drug in a broad patient population. At the time, Plenaxis was partnered with Thousand Oaks, Calif.-based Amgen Inc., which eventually left the partnership. (See BioWorld Today, June 13, 2001, and Sept. 20, 2001.)
Predictably, Praecis also has overseas ambitions for the drug. The company filed for European approval in June, and expects a decision between the middle and latter half of next year. Heiden said Praecis also expects to finalize a European marketing partnership during the first quarter of next year.
Development in Japan also would include a partner, which would aid in any further clinical study requirements on the part of local regulatory authorities. Heiden said such a partnership also would be finalized early next year.
The company's pipeline beyond Plenaxis includes Apan, an Alzheimer's drug candidate that is in a Phase Ib dose-escalation study. The peptide is designed as an inhibitor of the polymerization of beta-amyloid.
Praecis recently began Phase I studies of PPI-2458 in non-Hodgkin's lymphoma at the Dana-Farber Cancer Institute in Boston. The molecule inhibits called methionine aminopeptidase Type 2, an enzyme overexpressed in certain B-cell lymphomas. Data reported at last week's International Conference on Molecular Targets and Cancer Therapeutics in Boston pointed to the candidate's ability to treat a range of cancers.
Preclinical findings recently published in the American Journal of Rheumatology also described PPI-2458's ability to treat rheumatoid arthritis.
Praecis' stock (NASDAQ:PRCS) gained 95 cents Wednesday, or 14.2 percent, to close at $7.65.