ALPMY Astellas Pharma Inc (PK)

NORTHBROOK, Ill., May 5, 2015 /PRNewswire/ -- Astellas announced that two abstracts detailing clinical data from studies of enzalutamide and one abstract detailing clinical data from a study of mirabegron as an add-on treatment to solifenacin will be presented during a late breaking plenary session at the 2015 annual meeting of the American Urological Association (AUA) on May 17 in New Orleans, Louisiana.

New data from two Phase 2 studies designed to evaluate enzalutamide compared to bicalutamide in metastatic prostate cancer patients (TERRAIN) and metastatic and non-metastatic (STRIVE) prostate cancer patients whose disease progressed despite treatment with a luteinizing hormone-releasing hormone (LHRH) analogue therapy or following surgical castration will be presented. Also being presented during the late breaking plenary session are data from the Phase 3b BESIDE study, a randomized, double-blind, international study designed to evaluate the efficacy and safety of solifenacin with mirabegron as an add-on therapy in OAB patients.

About the TERRAIN Trial
The Phase 2 TERRAIN trial enrolled 375 patients in North America and Europe. The trial randomized patients with metastatic prostate cancer whose disease progressed despite treatment with a luteinizing hormone-releasing hormone (LHRH) analogue therapy or following surgical castration. The primary endpoint of the trial was progression-free survival, defined as time from randomization to centrally confirmed radiographic progression, skeletal related event, initiation of new anti-neoplastic therapy or death, whichever occurs first. The trial was designed to evaluate enzalutamide at a dose of 160 mg taken once daily versus bicalutamide at a dose of 50 mg taken once daily, the approved dose in combination with a LHRH analogue.

About the BESIDE Trial
The Phase 3b BESIDE study is a randomized, double-blind, international study designed to evaluate the efficacy and safety of mirabegron (MIRA) as add-on therapy to solifenacin (SOLI) in incontinent OAB patients.  Study patients received  SOLI 5 mg monotherapy for 4 weeks; subjects with inadequate response to treatment were then randomized to either SOLI 5 mg, SOLI 10 mg, or SOLI 5 mg in combination with MIRA 25 mg, which was increased to MIRA 50 mg after 4 weeks. Overall 2,174 patients were randomized to COMBN (n=727), SOLI 5 mg (n=728) or SOLI 10 mg (n=719). The primary efficacy endpoint was change from baseline to end of treatment (EoT) in mean number of incontinence episodes/24 hours.

About the STRIVE Trial
The Phase 2 STRIVE trial enrolled 396 castration-resistant prostate cancer patients in the United States. The trial randomized 257 patients with metastatic prostate cancer and 139 patients with non-metastatic prostate cancer whose disease progressed despite treatment with a luteinizing hormone-releasing hormone (LHRH) analogue therapy or following surgical castration.  The primary endpoint of the trial was progression-free survival, defined as time from randomization to radiographic (bone or soft tissue) progression, PSA progression (defined by Prostate Cancer Working Group 2 criteria), or death due to any cause, whichever occurs first.  The trial was designed to evaluate enzalutamide at a dose of 160 mg taken once daily versus bicalutamide at a dose of 50 mg taken once daily, the approved dose in combination with a LHRH analogue. 

About XTANDI^® (enzalutamide) capsules
XTANDI is approved by the U.S. Food and Drug Administration for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC).

Enzalutamide Mechanism of Action
Enzalutamide is an androgen receptor inhibitor that acts on three different steps in the androgen receptor signaling pathway.

Important Safety Information (from currently approved U.S. prescribing information)
Contraindications: XTANDI (enzalutamide) capsules can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. XTANDI is not indicated for use in women. XTANDI is contraindicated in women who are or may become pregnant.

Warnings and Precautions: In Study 1, conducted in patients with metastatic castration-resistant prostate cancer (CRPC) who previously received docetaxel, seizure occurred in 0.9% of patients who were treated with XTANDI and 0% treated with placebo. In Study 2, conducted in patients with chemotherapy-naïve metastatic CRPC, seizure occurred in 0.1% of patients who were treated with XTANDI and 0.1% treated with placebo. Patients experiencing a seizure were permanently discontinued from therapy and all seizure events resolved. There is no clinical trial experience readministering XTANDI to patients who experienced a seizure, and limited clinical trial experience in patients with predisposing factors for seizure. Study 1 excluded the use of concomitant medications that may lower threshold, whereas Study 2 permitted the use of these medications. Because of the risk of seizure associated with XTANDI use, patients should be advised of the risk of engaging in any activity during which sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

Adverse Reactions: The most common adverse reactions (>10%) reported from the two combined clinical trials that occurred more commonly (> 2% over placebo) in the XTANDI-treated patients were asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight decreased, headache, hypertension, and dizziness/vertigo.
Other Adverse Reactions include:

• Laboratory Abnormalities: In the two studies, Grade 14 neutropenia occurred in 15% of patients treated with XTANDI (1% Grade 3-4) and in 6% of patients treated with placebo (0.5% Grade 3-4). The incidence of Grade 14 thrombocytopenia was 6% of patients treated with XTANDI (0.3% Grade 3-4) and 5% of patients on placebo (0.5% Grade 3-4). Grade 1-4 elevations in ALT occurred in 10% of patients treated with XTANDI (0.2% Grade 3-4) and 16% of patients treated with placebo (0.2% Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of patients treated with XTANDI (0.1% Grade 3-4) and 2% of patients treated with placebo (no Grade 3-4).
• Infections: In Study 1, 1% of XTANDI versus 0.3% of placebo patients and in Study 2, 1 patient in each treatment group (0.1%) had an infection resulting in death.
• Falls: In the two studies, falls including fallrelated injuries occurred in 9% of XTANDI patients vs 4% treated with placebo. Falls were not associated with loss of consciousness or seizure. Fallrelated injuries were more severe in XTANDI patients and included nonpathologic fractures, joint injuries, and hematomas.
• Hypertension: In the two studies, hypertension was reported in 11% of patients receiving XTANDI and 4% of patients receiving placebo. No patients experienced hypertensive crisis. Medical history of hypertension was balanced between arms. Hypertension led to study discontinuation in < 1% of XTANDI or placebo treated patients.

Drug Interactions:

• Effect of Other Drugs on XTANDI  Administration of strong CYP2C8 inhibitors can increase the plasma exposure to XTANDI. Coadministration of XTANDI with strong CYP2C8 inhibitors should be avoided if possible. If coadministration of XTANDI cannot be avoided, reduce the dose of XTANDI. Coadministration of XTANDI with strong or moderate CYP3A4 and CYP2C8 inducers may alter the plasma exposure of XTANDI and should be avoided if possible.
• Effect of XTANDI on Other Drugs XTANDI is a strong CYP3A4 inducer and a moderate CYP2C9 and CYP2C19 inducer in humans. Avoid CYP3A4, CYP2C9 and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is coadministered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.

For Full Prescribing Information for XTANDI (enzalutamide) capsules, please visit http://www.XtandiHCP.com/PI

About Myrbetriq^® (mirabegron) extended-release tablets
INDICATIONS AND USAGE
Myrbetriq^® (mirabegron) is a beta- 3 adrenergic agonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency.

IMPORTANT SAFETY INFORMATION
Myrbetriq can increase blood pressure. Periodic blood pressure determinations are recommended, especially in hypertensive patients. Myrbetriq is not recommended for use in severe uncontrolled hypertensive patients (defined as systolic blood pressure > 180mm Hg and/or diastolic blood pressure > 110 mm Hg).

Urinary retention in patients with bladder outlet obstruction (BOO) and in patients taking antimuscarinic medications for the treatment of OAB has been reported in postmarketing experience in patients taking mirabegron. A controlled clinical safety study in patients with BOO did not demonstrate increased urinary retention in Myrbetriq patients; however, Myrbetriq should be administered with caution to patients with clinically significant BOO. Myrbetriq should also be administered with caution to patients taking antimuscarinic medications for the treatment of OAB.

Since Myrbetriq is a moderate CYP2D6 inhibitor, the systemic exposure to CYP2D6 substrates such as metoprolol and desipramine is increased when coadministered with Myrbetriq. Therefore, appropriate monitoring and dose adjustment may be necessary, especially with narrow therapeutic index drugs metabolized by CYP2D6, such as thioridazine, flecainide, and propafenone.

Most commonly reported adverse reactions (>2% and >placebo) for Myrbetriq 25 mg and 50 mg vs placebo, respectively, were hypertension (11.3%, 7.5% vs 7.6%), nasopharyngitis (3.5%, 3.9% vs 2.5%), urinary tract infection (4.2%, 2.9% vs 1.8%), and headache (2.1%, 3.2% vs 3.0%).

For Full Prescribing Information for Myrbetriq (mirabegron) extended–release tablets, please visit http://www.myrbetriqHCP.com.

About VESIcare^® (solifenacin succinate) tablets
INDICATION AND DOSAGE
VESIcare (solifenacin succinate) tablets are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency.  The recommended dose of VESIcare is 5 mg once daily.  If the 5-mg dose is well tolerated, the dose may be increased to 10 mg once daily.

IMPORTANT SAFETY INFORMATION
VESIcare is contraindicated in patients with urinary retention, gastric retention, uncontrolled narrow-angle glaucoma, and in patients with hypersensitivity to the product.

Angioedema of the face, lips, tongue and/or larynx have been reported with VESIcare.  Cases of angioedema have been reported to occur hours after the first dose or after multiple doses.  Angioedema associated with upper airway swelling may be life threatening.  If involvement of the tongue, hypopharynx, or larynx occurs, VESIcare should be promptly discontinued and appropriate therapy and/or measures necessary to ensure a patent airway should be promptly provided.  Anaphylactic reactions have been reported rarely in patients treated with VESIcare.  VESIcare should not be used in patients with a known or suspected hypersensitivity to solifenacin succinate.  In patients who develop anaphylactic reactions, VESIcare should be discontinued and appropriate therapy and/or measures should be taken.

VESIcare should be administered with caution to patients with clinically significant bladder outflow obstruction, decreased gastrointestinal motility, controlled narrow-angle glaucoma, or reduced renal or hepatic function.  Doses of VESIcare higher than 5 mg are not recommended in patients with severe renal impairment, moderate hepatic impairment, or when administered with ketoconazole or other potent CYP3A4 inhibitors.  Use of VESIcare in patients with severe hepatic impairment is not recommended.

Anticholinergic central nervous system (CNS) effects have been reported with VESIcare use, including headache, confusion, hallucinations and somnolence.  Patients should be monitored for signs of anticholinergic CNS effects, particularly after beginning treatment or increasing dose, and be advised not to drive or operate heavy machinery until they know how VESIcare affects them.  If a patient experiences these effects, dose reduction or drug discontinuation should be considered.

In placebo-controlled studies, for the 10-mg dose, three intestinal serious adverse events were reported (one fecal impaction, one colonic obstruction, and one intestinal obstruction).  For the 5-mg dose, one serious adverse event (angioneurotic edema) was reported.

In placebo-controlled studies, the most common adverse reactions reported by patients were dry mouth (10.9%, 27.6%, 4.2%), constipation (5.4%, 13.4%, 2.9%), blurred vision (3.8%, 4.8%, 1.8%), and urinary tract infection (2.8%, 4.8%, 2.8%) with VESIcare 5 mg, 10 mg, and placebo, respectively.

For Full Prescribing Information for VESIcare (solifenacin succinate) tablets, please visit http://www.vesicareHCP.com.

XTANDI^®, Myrbetriq^® and VESIcare^® are trademarks of Astellas Pharma Inc.
*All other trademarks or registered trademarks are the property of their respective owners.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1800FDA1088.

About Astellas
Astellas is a pharmaceutical company dedicated to improving the health of people around the world through provision of innovative and reliable pharmaceuticals. For more information on Astellas, please visit our website at www.astellas.us, follow us on Twitter at www.twitter.com/AstellasUS or like our Facebook page at www.facebook.com/AstellasUS.

About the Medivation/Astellas Collaboration
In October 2009, Medivation (NASDAQ: MDVN) and Astellas (Tokyo: 4503) entered into a global agreement to jointly develop and commercialize enzalutamide. The companies are collaborating on a comprehensive development program that includes studies to develop enzalutamide across the full spectrum of advanced prostate cancer as well as advanced breast cancer. The companies jointly commercialize XTANDI in the United States and Astellas has responsibility for manufacturing and all additional regulatory filings globally, as well as commercializing XTANDI outside the United States.

Astellas Contacts:
For Media
Christy Noland (BESIDE)
(224) 205-5735
christina.noland@astellas.com

Tyler Marciniak (TERRAIN, STRIVE)
(847) 736-7145
tyler.marciniak@astellas.com

For Investors
So Sekine
+81-3-3244-3202
sou.sekine@astellas.com

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SOURCE Astellas