Astellas Announces New Enzalutamide Data Presented During Plenary Presentations at the 2015 European Association of Urol

LONDON, March 24, 2015 /PRNewswire/ --

Astellas Pharma Europe Ltd. today announced new data from the Phase 2 TERRAIN trial of enzalutamide compared to bicalutamide in metastatic castration-resistant prostate cancer (CRPC), as well as an updated overall survival analysis from the placebo-controlled Phase 3 PREVAIL trial of enzalutamide in chemotherapy-naive metastatic CRPC. The data were presented during a plenary session at the 2015 European Association of Urology (EAU) Congress in Madrid, Spain.

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"The late breaking data presented at this year's EAU Congress further demonstrate the breadth and depth of the enzalutamide development programme," said Claire Thom, Pharm.D., Senior Vice President and Oncology Therapeutic Head, Astellas Pharma Global Development, Inc. "We are encouraged to see that enzalutamide continues to generate promising data for men with advanced prostate cancer and their loved ones."

Highlights of Key Enzalutamide Data

Title: A randomized, double-blind, Phase 2, efficacy and safety study of enzalutamide vs. bicalutamide in metastatic castrate resistant prostate cancer: TERRAIN trial[1]

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

"The results of the TERRAIN trial, if confirmed, have the potential to impact the treatment landscape of metastatic castration-resistant prostate cancer," said Axel Heidenreich, M.D., Ph.D., Professor and Director, Department of Urology, University hospital, Aachen, Germany. "The study demonstrated an improvement with enzalutamide over the standard practice of the addition of bicalutamide to a luteinising hormone-releasing hormone (LHRH) therapy."

- The study achieved its primary objective of a statistically significant
increase in PFS for enzalutamide compared to bicalutamide. The median PFS in the
enzalutamide arm was 9.9 months longer compared to that in the bicalutamide arm (15.7
vs 5.8 months, respectively) with a Hazard Ratio (HR) of 0.44 (95% confidence
interval, 0.34-0.57; p<0.0001);
- The median time to PSA progression was 13.6 months longer with enzalutamide
(19.4 months) relative to bicalutamide treatment (5.8 months) with a HR of 0.28
(p<0.0001);
- 82% of enzalutamide-treated patients achieved greater than or equal to 50% PSA
reduction from baseline by week 13 vs 21% of bicalutamide-treated patients;
- The median time on enzalutamide treatment was 11.7 months compared to 5.8
months on bicalutamide;
- The safety profile of the enzalutamide-treated patients in TERRAIN is
consistent with the known safety profile of enzalutamide.
- Serious adverse events (AEs) were reported in 31.1% of enzalutamide vs
23.3% bicalutamide patients and Grade 3 or higher cardiac AEs were observed in
5.5% of enzalutamide vs 2.1% of bicalutamide patients. Two seizures were reported
with enzalutamide and 1 with bicalutamide;
- The common (greater than or equal to10%) AEs reported more frequently with
enzalutamide vs bicalutamide were fatigue (27.9% vs 20.1%), back pain (19.1% vs
18.0%), hot flush (14.8% vs 11.1%), hypertension (14.2% vs 7.4%), diarrhea (11.5%
vs 9.0%), weight decreased (10.9% vs 7.9%) and pain in extremities (10.9% vs
5.3%).

Title: Enzalutamide in men with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC): Final overall survival analysis of the Phase 3 PREVAIL study[2]

The Phase 3 PREVAIL trial, a randomised, double-blind, placebo-controlled, multi-national trial, enrolled 1,717 patients at sites in the United States, Canada, Europe, Australia, Russia, Israel and Asia, including Japan. The trial enrolled patients with chemotherapy-naïve metastatic prostate cancer whose disease progressed on androgen deprivation therapy (i.e., a LHRH therapy or after bilateral orchiectomy). The co-primary endpoints of the trial were overall survival and radiographic progression-free survival. The trial was designed to evaluate enzalutamide at a dose of 160 mg taken orally once daily versus placebo.

"The most interesting observations around these data are that enzalutamide achieved significant overall survival despite many patients receiving additional treatment, and that the diagnosis of when a patient's disease becomes metastatic, which drives the timing of therapy initiation, is important," said Bertrand Tombal, M.D., Ph.D., Professor and Chairman, Department of Urology, Universite catholique de Louvain, Cliniques universitaires Saint-Luc, Brussels. "The standard approach, as done in the placebo arm of PREVAIL, is to wait usually for some symptoms or rapid radiological progression before initiating chemotherapy. However, this study demonstrated that starting patients on enzalutamide at the point when their castration-resistant prostate cancer becomes metastatic has the potential to prolong survival."

- An updated overall survival analysis was conducted at 784 deaths and found
a statistically significant overall survival benefit with a 23% reduction in risk of
death (OS: HR 0.77; 95% CI 0.67-0.88; P=0.0002) and a 4-month improvement in median
survival with enzalutamide (35.3 months [95% CI 32.2-not yet reached]) over placebo
(31.3 months [95% CI 28.8-34.2]). As of the June 2014 cut-off date with a median
follow-up duration of 31 months:
- 52% of enzalutamide and 81% of placebo patients received greater than or
equal to1 subsequent life-extending prostate cancer therapy.

About XTANDI(TM) (enzalutamide)

Enzalutamide is a novel, oral, once-daily androgen receptor signaling inhibitor. Enzalutamide directly targets the androgen receptors (AR) and exerts its effects on all three steps of AR signaling pathway:

- Blocks androgen binding[3]
- Androgen binding induces a conformational change that triggers activation
of the receptor[4]
- Prevents nuclear translocation[3]
- Transit of the AR to the nucleus is an essential step in AR-mediated gene
regulation[4]
- Impairs DNA binding[3]
- Binding of the AR to the DNA is essential for modulation of gene
expression[4]

Enzalutamide was first approved by the European Commission in June 2013 for the treatment of adult men with mCRPC whose disease has progressed on or after docetaxel therapy.[5] Enzalutamide is now approved in Europe for the treatment of adult men with metastatic castration-resistant prostate cancer who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated.[5]

Important Safety Information for XTANDI(TM) (enzalutamide)

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