Overview

Medivation's business is built on the identification and rapid development of product candidates that have the potential to improve the standard of care in human diseases.


Ongoing Clinical Studies


Drug/Indication
Phase 1
Phase 2
Phase 3
Phase 4

Enzalutamide
Prostate Cancer
STRIVE   PROSPER   EMBARK   PLATO   AFFIRM*   PREVAIL*   TERRAIN*   Breast Cancer
AR+ TNBC
ER+ or PgR+ &
HER2 normal

AR+ HER2 Amplified
 
 
 
 

 

 

*Open label extension trials: trials unblinded and placebo-treated (or bicalutamide-treated) patients crossed over to enzalutamide.

Enzalutamide

Medivation, in collaboration with Astellas, is currently developing enzalutamide for multiple stages of prostate cancer and for breast cancer.

Prostate Cancer


STRIVE

In April 2015, we and Astellas reported top-line results from the Phase 2 STRIVE trial. The study achieved its primary endpoint demonstrating a statistically significant increase in progression-free survival (PFS) for enzalutamide compared with bicalutamide (Hazard Ratio = 0.24; 95% Confidence Interval, 0.18-0.32; p < 0.0001). Median PFS was 19.4 months in the enzalutamide group compared with 5.7 months in the bicalutamide group. The median time on treatment in the STRIVE trial was 14.7 months in the enzalutamide group versus 8.4 months in the bicalutamide group. Serious adverse events were reported in 29.4% of enzalutamide-treated patients and 28.3% of bicalutamide-treated patients. Grade 3 or higher cardiac adverse events were reported in 5.1% of enzalutamide-treated patients versus 4.0% of bicalutamide-treated patients. One seizure was reported in the trial in the enzalutamide-treated group and none in the bicalutamide-treated group. Additional data from the STRIVE trial, including the secondary endpoints and further safety data, has been submitted for presentation at upcoming medical conferences. The Phase 2 STRIVE trial is a non-registrational clinical trial and the data from the STRIVE trial are not expected to be approved for use in XTANDI marketing and promotion.

PROSPER

The first patient was enrolled in the Phase 3 PROSPER trial in December 2013. The trial is evaluating the safety and efficacy of enzalutamide in patients with non-metastatic CRPC. The PROSPER trial is intended to enroll a high-risk subgroup of patients with prostate cancer who are progressing despite androgen deprivation therapy, but who are asymptomatic with no prior or present evidence of metastatic disease. The Phase 3 randomized, double-blind, placebo-controlled, multi-national trial is designed to enroll approximately 1,560 patients with non-metastatic CRPC. The primary endpoint of the trial is metastasis-free survival

EMBARK

The first patient was enrolled in the Phase 3 EMBARK trial in January 2015. The trial is intended to evaluate the efficacy and safety of enzalutamide in patients with high-risk, hormone-sensitive, non-metastatic prostate cancer that has biochemically recurred (rising PSA level) following definitive local therapy with radical prostatectomy and/or radiation. The purpose of the trial is to help determine if enzalutamide can delay or prevent the development of metastatic prostate cancer in high-risk men with a rapidly rising PSA. The primary endpoint of the trial is metastasis-free survival. The trial is designed to enroll approximately 1,860 patients.

PLATO

The Phase 4 PLATO trial was initiated in November 2013 and completed enrollment in September 2014. The trial is evaluating the efficacy and safety of continued treatment with enzalutamide plus abiraterone acetate and prednisone as compared to abiraterone acetate and prednisone alone in patients with chemotherapy-naive metastatic prostate cancer whose disease has progressed following enzalutamide therapy. The purpose of the trial is to help determine the potential clinical benefit of extending time on enzalutamide treatment by adding an additional therapy in patients with progressive chemotherapy-naive metastatic prostate cancer. The global randomized, double-blind, placebo-controlled trial has enrolled 509 chemotherapy-naive patients with mCRPC. The primary endpoint of the trial is PFS.

AFFIRM

Our FDA approval in post-chemotherapy mCRPC was based on the results of the AFFIRM trial, a randomized, double-blind Phase 3 trial evaluating XTANDI (160 mg once daily) as compared to placebo in 1,199 post-chemotherapy mCRPC patients. The primary endpoint of the AFFIRM trial was overall survival. Data from the AFFIRM trial were first reported in November 2011 and were published in The New England Journal of Medicine in August 2012. The AFFIRM trial also led to the initial marketing approvals of XTANDI by regulatory authorities in Europe and Japan. The open-label extension of this trial is ongoing.

PREVAIL

Our FDA approval in pre-chemotherapy mCRPC was based on the results of the PREVAIL trial, a randomized, double-blind, placebo-controlled Phase 3 trial, evaluating enzalutamide (160 mg once daily) as compared to placebo in approximately 1,717 patients with pre-chemotherapy mCRPC. The PREVAIL trial included patients who had progressed following treatment with an LHRH analog drug only, as well as patients who had progressed following treatment with both an LHRH analog drug and an anti-androgen drug. The co-primary endpoints were radiographic PFS and overall survival. Positive results from the PREVAIL trial were first reported in October 2013 and were published in The New England Journal of Medicine in June 2014. The PREVAIL trial also led to expanded marketing approvals by regulatory authorities in Europe, Japan, and numerous other countries worldwide. The open-label extension of this trial is ongoing.

TERRAIN

In January 2015, we and Astellas reported top-line results from the Phase 2 TERRAIN trial. The trial achieved its primary endpoint demonstrating a statistically significant increase in PFS for patients with mCRPC for enzalutamide compared to bicalutamide (Hazard Ratio = 0.44; 95% Confidence Interval, 0.34-0.57; p < 0.0001). The median time on treatment in the TERRAIN trial was 11.7 months in the enzalutamide group versus 5.8 months in the bicalutamide group. Median PFS was 15.7 months in the enzalutamide group compared to 5.8 months in the bicalutamide group. Serious adverse events were reported in 31.1% of enzalutamide-treated patients and 23.3% of bicalutamide-treated patients. Grade 3 or higher cardiac adverse events were reported in 5.5% of enzalutamide-treated patients versus 2.1% of bicalutamide-treated patients. Two seizures were reported in the enzalutamide group and one in the bicalutamide group. Additional data from the TERRAIN trial, including the secondary endpoints and further safety data, has been submitted for presentation at upcoming medical conferences. The Phase 2 TERRAIN trial is a non-registrational clinical trial and the data from the TERRAIN trial are not expected to be approved for use in XTANDI marketing and promotion. The open-label extension of the trial is ongoing.

Breast Cancer


In April 2012, we and Astellas expanded the clinical development of enzalutamide to include breast cancer. We currently have three Phase 2 clinical trial evaluating enzalutamide in three subsets of breast cancer. Information about our breast cancer clinical trials is included below:

AR+ TNBC

In June 2013, we and Astellas initiated a Phase 2 clinical trial evaluating enzalutamide as a single agent for the treatment of advanced androgen receptor positive (AR+), triple negative breast cancer (TNBC). TNBC is a type of breast cancer that is not driven by the three most commonly targeted receptors in breast cancer: estrogen, progesterone and human epidermal growth factor receptor 2, or HER2. The Phase 2 open label, single arm, multicenter trial enrolled 118 women in two stages with metastatic TNBC in sites in the United States, Canada, and Europe. The primary endpoint of the trial is clinical benefit rate defined as the proportion of women with a complete response, partial response or stable disease for at least 16 weeks. Patients with any amount of AR expression in their primary tumor were enrolled, but to be evaluable for the primary endpoint analysis, at least 10% of the cells in the patient’s primary tumor sample must test positive for the androgen receptor. Additionally, we are optimizing a diagnostic test that may help best identify those most likely to receive clinical benefit from enzalutamide. Data from stage 1 of the trial and preliminary data from stage 2 of the trial were presented at the 37th Annual San Antonio Breast Cancer Symposium in December 2014. Mature data from the Phase 2 trial are anticipated in 2015. Although we believe the early data are encouraging, particularly in this population of women who have limited treatment options, no firm determination has been made by us or Astellas at this time about the conduct of later-stage studies in this population.

ER+ or PgR+ & HER2 normal

In December 2013, we and Astellas initiated a Phase 2 clinical trial evaluating enzalutamide in combination with exemestane in women with advanced breast cancer that is estrogen receptor positive (ER+) or progesterone receptor positive (PgR+) and HER2 normal. The Phase 2 randomized, double-blind, placebo-controlled, multicenter trial is intended to assess 240 patients in two parallel cohorts of 120 patients each. The first cohort is intended to enroll patients who have not previously received hormonal treatment for advanced breast cancer. The second cohort is intended to enroll patients who have previously progressed following one hormonal treatment for advanced disease. The primary endpoint of the trial is PFS in patients and in the subset of patients whose tumor expresses the androgen receptor.

AR+ and HER2 Amplified

In August 2014, we and Astellas initiated a Phase 2 clinical trial evaluating the safety and efficacy of adding enzalutamide to trastuzumab in approximately 80 patients with metastatic or locally advanced breast cancer that is AR+, HER2 amplified, and estrogen-receptor negative (ER-) or progesterone receptor negative (PgR-) whose disease has previously progressed on trastuzumab. The primary endpoint of the trial is clinical benefit rate defined as complete response or partial response or stable disease at or before 24 weeks. The goal of the trial is to determine whether enzalutamide will provide any incremental benefit for women who have progressed on trastuzumab.

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