Seeking Approval for NEBIDO to Treat Male Hypogonadism
LEXINGTON, Mass., Aug. 28 /PRNewswire-FirstCall/ -- Indevus Pharmaceuticals, Inc. (Nasdaq: IDEV) today announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking approval for NEBIDO(R) (testosterone undecanoate) intramuscular injection, a long-acting testosterone therapy intended to treat male patients with primary and secondary hypogonadism. Each 1000 mg injection of NEBIDO would only need to be provided once every 12 weeks, as compared to the current injectable therapies which typically require an injection every two to three weeks.
The NDA submission follows the June 2007 announcement of positive results from the Company's Phase III pharmacokinetic trial for NEBIDO. In addition to the data from this U.S. trial, the NDA includes the results of the European clinical trials database (originally generated by the Company's partner, Bayer Schering Pharma AG, Germany) which has formed the basis for the approval of NEBIDO in over 75 countries to date.
The U.S. testosterone therapy market is currently estimated to be in excess of $550 million. Of the approximately 340,000 men currently receiving therapy, approximately 130,000 utilize the existing injectable therapies that must be given every two to three weeks.
The NDA contains data from six clinical studies in which over 400 patients received at least one dose of NEBIDO, with over 300 of these patients treated for more than one year. In total, over 3,000 injections of NEBIDO have been given to hypogonadal males during the clinical development program. In addition, the NDA includes post-marketing data from safety reporting through June 2007, reflecting the world-wide experience from over 260,000 injections of NEBIDO.
"The submission of the NEBIDO NDA is a very important milestone for the Company," said Glenn L. Cooper, M.D., chief executive officer and chairman of Indevus. "We strongly believe that NEBIDO can greatly improve the treatment options for men who suffer from hypogonadism."
Phase III Pharmacokinetic Trial
In June 2007, the Company announced positive results of its Phase III pharmacokinetic trial with NEBIDO. The purpose of the trial was to evaluate NEBIDO under U.S. Food and Drug Administration (FDA) pharmacokinetic guidelines for the approval of testosterone therapy products for male hypogonadism. The trial met its primary endpoints: a responder analysis based on the average testosterone concentrations during the steady-state dosing interval and an outlier analysis based on the maximum testosterone concentrations during the steady-state dosing interval.
Phase III Study Design
The Phase III pharmacokinetic trial was a randomized open-label (unblinded) study that included the evaluation of the pharmacokinetics of NEBIDO dosed as either 1000 mg every 12 weeks or as 750 mg every 12 weeks, both via intramuscular injection. The primary endpoints included a responder analysis (based on guidelines provided from the FDA for average testosterone concentrations over the steady state dosing interval) and an outlier analysis (based on the maximum testosterone concentrations during the steady state dosing interval). Specifically, a responder was defined (per the FDA) as a patient who, at steady-state conditions, had an average concentration of serum total testosterone (Cavg) within the normal range (300 to 1000 ng/dL). The primary response endpoint was met if at least 75% of patients achieved a Cavg within this normal range. FDA also provided guidelines related to maximum testosterone (Cmax) levels, including thresholds that no patient should exceed a testosterone concentration of 2500 ng/dL, no more than 5% of patients should exceed a concentration of 1800 ng/dL, and no more than 15% of patients should exceed a concentration of 1500 ng/dL.
In addition, secondary outcomes included measurements evaluating the general health and well-being of the patients by questionnaires and assessment tools.
Phase III Study Findings
The trial randomized a total of 237 male hypogonadal patients (117 patients treated in the 1000 mg dose arm and 120 patients treated in the 750 mg dose arm). The patient completion rate of all 5 injections with NEBIDO was over 80%, demonstrating very high treatment compliance for a one-year study. Reasons for discontinuation were similar between the treatment groups.
Of the 97 patients in the 1000 mg arm receiving their steady-state injection, 94% had a Cavg over the course of the 12-week period that was within the normal range, demonstrating that treatment with NEBIDO successfully maintained therapeutic testosterone levels in hypogonadal men with injections given only once every 12 weeks (just 4 to 5 times per year). Further, no patients in the 1000 mg arm exceeded a testosterone concentration of 2500 ng/dL; four of 97 (4.1%) patients had a peak level over 1800 ng/dL; and 11 of 97 (11.3%) patients had a peak level exceeding 1500 ng/dL. The duration of time any patient had a concentration over these Cmax thresholds was brief.
Of the 102 patients in the 750 mg arm receiving their fourth injection, 86% had a Cavg within the normal range. No patients in the 750 mg arm exceeded a testosterone level of either 2500 ng/dL or 1800 ng/dL, and only four of 102 (3.9%) patients had a peak level exceeding 1500 ng/dL. For those few patients exceeding the 1500 ng/dL threshold, the duration of time above the threshold was brief.
Both treatment arms demonstrated improvements from baseline in key secondary clinical outcome variables.
Both doses of the drug were well-tolerated as indicated by the analysis of the safety measurements collected and the persistence with study treatment. Further, the spectrum of adverse events reported were comparable to other injectable hypogonadism treatments reported in the literature. There were no significant adverse changes in laboratory parameters with NEBIDO treatment.
NEBIDO(R) is a long-acting depot preparation of testosterone undecanoate, developed for the treatment of male hypogonadism. NEBIDO is expected to be the first three-month testosterone preparation available in the U.S. in the growing market for testosterone therapies. Indevus acquired U.S. rights to NEBIDO from Bayer Schering Pharma AG, Germany in July 2005.
Male hypogonadism is an increasingly recognized medical condition characterized by a reduced or absent secretion of testosterone from the testes. Reduced testosterone levels can lead to health problems and significantly impair quality of life. Common effects of hypogonadism include decreased sexual desire, muscle loss and weakness, as well as an increased risk of osteoporosis. Today, there are an estimated four to five million men in the U.S. who suffer from hypogonadism. Of this group, less than ten percent are currently receiving treatment with testosterone therapy.
Indevus Pharmaceuticals, Inc. is a specialty pharmaceutical company engaged in the acquisition, development and commercialization of products to treat conditions in urology and endocrinology. The Company's approved products include SANCTURA(R) XR and SANCTURA(R) for overactive bladder, VANTAS(R) for advanced prostate cancer, SUPPRELIN(R) LA, for central precocious puberty, and DELATESTRYL(R) to treat male hypogonadism. The Indevus development pipeline contains multiple compounds within the Company's core therapeutic areas in addition to several partnered or partnerable programs. The most advanced compounds in development include, VALSTAR(R) for bladder cancer, NEBIDO(R) for male hypogonadism, PRO 2000 for the prevention of infection by HIV and other sexually-transmitted pathogens, and pagoclone for stuttering.
Forward Looking Statements
Except for the descriptions of historical facts contained herein, this press release contains forward-looking statements that involve risks and uncertainties that could cause the Company's actual results and financial condition to differ materially from those anticipated by the forward-looking statements. These risks and uncertainties are set forth in the Company's filings under the Securities Act of 1933 and the Securities Exchange Act of 1934 under "Risk Factors" and elsewhere, and include, but are not limited to: dependence on the success of SANCTURA(R), SANCTURA(R) XR, NEBIDO(R) , VANTAS(R) and SUPPRELIN(R) LA; the early state of products under development; uncertainties relating to clinical trials, regulatory approval and commercialization of our products, particularly SANCTURA XR, NEBIDO, and VALSTAR(R); risks associated with contractual agreements, particularly for the manufacture and co-promotion of SANCTURA and SANCTURA XR and the manufacture of NEBIDO, VANTAS, SUPPRELIN LA and VALSTAR; dependence on third parties for supplies, particularly for histrelin, manufacturing, marketing, and clinical trials; competition; need for additional funds and corporate partners, including for the development of our products; failure to acquire and develop additional product candidates; changes in reimbursement policies and/or rates for SANCTURA, VANTAS, SUPPRELIN LA, DELATESTRYL(R) and any future products; history of operating losses and expectation of future losses; product liability and insurance uncertainties; risks relating to the Redux- related litigation; the risk that the businesses of Indevus and Valera Pharmaceuticals, Inc. will not be integrated successfully during the period following the related merger; the risk that the cost savings and any other synergies from the merger may not be fully realized or may take longer to realize than expected; market acceptance for the merger and approved products; risks of regulatory review and clinical trials; disruption from the transaction making it more difficult to maintain relationships with customers, employees or suppliers; competition and its effect on pricing, spending, third-party relationships and revenues; reliance on intellectual property and having limited patents and proprietary rights; dependence on market exclusivity, valuation of our Common Stock; risks related to repayment of debts; risks related to increased leverage; general worldwide economic conditions and related uncertainties; the effect of changes in governmental regulations and other risks. Indevus undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.
Michael W. Rogers Brooke D. Wagner
Executive Vice President and CFO VP, Corp. Communications
(781) 861-8444 (781) 402-3410
|SOURCE Indevus Pharmaceuticals, Inc.|
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