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Approval sought for two new indications for quinolone

Ortho-McNeil, Inc. has filed a supplemental new drug application with the FDA for new indications of levofloxacin (Levaquin), 750 mg tablets: acute pyelonephritis and complicated urinary tract infections. The filing is based on a clinical trial evaluating the safety and efficacy of IV/oral levofloxacin, 750 mg once daily for 5 days, compared with IV/oral ciprofloxacin (Cipro), 500 mg twice daily for 10 days, in more than 1,100 patients with acute pyelonephritis or complicated UTIs.

The application supports the use of levofloxacin in infections caused by Enterococcus faecalis, Enterobacter cloacae, Escherichia coli (including cases with bacteremia), Klebsiella pneumoniae, Proteus mirabilis, or Pseudomonas aeruginosa. Once approved, the new formulation will be marketed by PriCara, a unit of Ortho-McNeil.

The FDA has accepted for filing and has assigned priority review status to the biologics license application (BLA) for sipuleucel-T (Provenge), Dendreon Corp.'s investigational active cellular immunotherapy for the treatment of asymptomatic, metastatic, androgen-independent prostate cancer.

The goal for reviewing a product with priority review status is 6 months from the filing date. The Prescription Drug User Fee Act date for completion of review by the FDA of the sipuleucel-T BLA is May 15, 2007.

The BLA submission is predicated on a double-blind, placebo-controlled, phase III study (D9901) in men with hormone-refractory prostate cancer. Median survival was 4.5 months longer in men who received sipuleucel-T than in those who received placebo, and those in the sipuleucel-T group had a 41% overall reduction in risk of death (J Natl Cancer Inst 2006; 24:3089-94).

Phase III study of LHRH antagonist in BPH begins

Æterna Zentaris, Inc. has begun the first of three phase III studies investigating the safety and efficacy of its luteinizing hormone-releasing hormone antagonist compound, cetrorelix, in men with BPH. This multicenter, 600-patient, placebo-controlled study will assess the safety and tolerability of an intermittent dosage regimen of the LHRH agent in inducing absolute change in International Prostate Symptom Score between baseline before treatment and week 52.

Safety endpoints will include changes in sexual function and BPH symptom progression equal to four or more points and/or acute urinary retention and/or need for BPH-related surgery.

A second, similar study, will involve 300 men at multiple centers, and will commence in the first half of 2007. The third study, an open-label, single-arm safety study in 600 men, will begin at multiple centers later this year.

New drug application filed for investigational antibiotic

Johnson & Johnson Pharmaceutical Research & Development, LLC, has submitted a new drug application to the FDA for the investigational antibiotic doripenem in treating complicated urinary tract infections and complicated intra-abdominal infections. The agent is in the class of carbapenems, which have demonstrated effectiveness in treating gram-positive and resistant gram–negative bacteria.

If approved, doripenem will be marketed in the United States by Ortho-McNeil, Inc.

Agent for advanced RCC is given priority review status

Wyeth Pharmaceuticals' new drug application for temsirolimus (Torisel) has been accorded priority review status by the FDA. The company is seeking an indication for the investigational agent in the treatment of advanced renal cell carcinoma. FDA had previously granted the agent fast track designation and orphan drug status in RCC.

The designation was granted on the basis of data from a three-arm, phase III clinical trial in 626 patients with RCC who had received no prior systemic therapy. Temsirolimus significantly increased overall survival in 49% in patients compared with those who were treated with interferon-alpha.

Temsirolimus specifically inhibits the mTOR kinase, a protein that regulates cell proliferation, growth, and survival.