The US Food and Drug Administration has approved ALZA Corporation’s new drug application for a
The US Food and Drug Administration has approved ALZA Corporations new drug application for a once-yearly leuprolide acetate implant (Viadur) for the palliative treatment of advanced prostate cancer. The implant is the first product to provide continuous 12-month testosterone suppression with a single treatment. It is also the first approved product to incorporate ALZAs proprietary implant technology.
We are extremely pleased with the rapid clinical development of Viadur, said Samuel R. Saks, MD, group vice president, ALZA Pharmaceuticals. Viadur is a unique product that will provide an important new therapeutic option to patients with advanced prostate cancer.
Viadur is a drug-filled, miniature titanium cylinder that is placed under the skin in the inner aspects of the patients upper arm during an in-office surgical procedure. The product contains an osmotic engine that continuously delivers precise levels of leuprolide for 1 year, thus providing an alternative to frequent leuprolide injections.
Role of Testosterone Suppression Therapy
Testosterone suppression or hormonal therapy is commonly used for the palliative treatment of advanced stages of prostate cancer, and continuous testosterone suppression is usually required for many months or years in this setting. Leuprolide is part of a class of drugs known as luteinizing hormone-releasing hormone (LHRH) agonists that work by decreasing the amount of testosterone produced by the body.
Leuprolide is well established as a palliative treatment for advanced prostate cancer, and the once-yearly dosing regimen provided by Viadur may present a convenient alternative for patients, said James Gottesman, MD, clinical professor of Urology at the University of Washington Medical School in Seattle. Currently, therapeutic suppression of testosterone levels is primarily achieved through intramuscular depot injections administered once every 1, 3, or 4 months.
Demonstrated Efficacy and Safety
In two open-label, multicenter studies, 131 patients with advanced prostate cancer were treated with Viadur and evaluated for up to 2 years. Following the initial surgical insertion of the implant, mean serum testosterone concentrations decreased to therapeutically desirable levels by week 4 in 99% of the patients in the study. Once serum testosterone suppression was achieved, testosterone levels remained suppressed for the duration of the 12-month treatment phase.
Following removal of the first implant, 118 patients had a new implant inserted for a second year of therapy. No patient experienced a clinically significant rise in serum testosterone upon removal of the original implant and insertion of the new one.
Serum prostate-specific antigen (PSA) was monitored as a secondary end point in the two clinical studies. Overall, after Viadur treatment was started, concentrations of PSA decreased in the study population.
In clinical trials, the most common treatment-related side effects were those expected with LHRH agonists, including vasodilation (67.9%), asthenia (7.6%), gynecomastia (6.9%), depression (5.3%), and sweating (5.3%). Local application site reactions reported by patients after insertion or removal of the implant included bruising (34.8%) and burning (5.6%). Local reactions developed in 10% of patients the first 2 weeks after insertion, and the majority of those reactions also resolved within the first 2 weeks. Reactions persisted in 9.3% of patients.
Like other LHRH agonists, leuprolide causes a transient increase in serum concentrations of testosterone during the first week of treatment. Patients may experience worsening of symptoms or onset of new symptoms, manifested by pain or bladder outlet obstruction.