Orteronel Plus Prednisone Improved Progression Free Survival in Men With Chemotherapy-Na�ve Metastatic Castration Resistant Prostate Cancer in Phase 3 Study

Takeda Pharmaceutical Company Limited (TSE:4502) today announced data
from ELM-PC4, a pivotal, international, double blind, randomized Phase 3
trial showing that the investigational drug orteronel plus prednisone
reduced the risk of radiographic progression free survival (rPFS), one
of the study’s two primary endpoints, by 30 percent compared to placebo
plus prednisone in men with chemotherapy-naïve metastatic castration
resistant prostate cancer (mCRPC) [median rPFS 11.0 v. 8.3 months (HR
0.7; 95% CI:0.5-0.8; P<0.001)]. The second primary endpoint, overall
survival (OS), showed a numerical improvement in median OS of 1.9 months
that was not statistically significant [median OS: 31.4 vs. 29.5 months
(HR 0.9; 95% CI: 0.8-1.1; P=0.314)]. Results from the study will be
presented as an oral presentation on June 1 during the Genitourinary
(Prostate) Cancer session at the annual meeting of the American Society
of Clinical Oncology (ASCO).

“The significant rPFS advantage observed for orteronel combined with
prednisone in the ELM-PC4 study is consistent with the previously
reported rPFS improvement observed in the ELM-PC5 study, where orteronel
was also studied with prednisone in men with mCRPC who had previously
received chemotherapy. We are carefully analyzing these data to fully
inform future decisions in the orteronel program,” said Michael
Vasconcelles, M.D., Global Head, Takeda Oncology Therapeutic Area Unit.
“We thank and express our gratitude to the patients, their families and
the study investigators for their significant contributions to the
orteronel program to date.”

The abstract, titled “Phase 3, randomized, placebo-controlled trial of
orteronel (TAK-700) plus prednisone in patients (pts) with
chemotherapy-naïve metastatic castration-resistant prostate cancer
(mCRPC) (ELM-PC 4 trial) [Abstract #5008]”, compared orteronel 400 mg
twice daily (BID) plus prednisone 5 mg BID to placebo plus prednisone in
1,560 men with progressive chemotherapy-naïve mCRPC (rising PSA and/or
radiographic evidence of metastases) and serum testosterone <50 ng/dL
post orchiectomy or with maintained GnRH suppression. In the study, men
with progressive mCRPC were randomized 1:1 to either treatment or
control groups. The final analysis for rPFS was conducted at an interim
analysis for OS, and the final analysis for OS was conducted at 600
deaths. The results will be presented by Ronald DeWit, MD, PhD, Erasmus
MC Cancer Institute. Key secondary endpoints showed more patients
experienced at least a 50 percent decrease in prostate-specific antigen
and favorable circulating tumor cell (CTC) counts at 12 weeks in the
treatment arm compared to the control. Common all-grade adverse events
with orteronel and prednisone compared tocontrol included nausea
(36% vs. 15%), fatigue (34% vs. 20%), constipation (33% vs. 15%) and
diarrhea (28% vs. 14%); 30 percent vs. 18 percent of patients in the
orteronel arm and control arm, respectively, discontinued due to adverse
events. No new safety signals attributed to orteronel were identified in
this study.

Orteronel, discovered by Takeda, is an investigational oral,
non-steroidal, selective inhibitor of 17,20-lyase, a key enzyme in the
production of steroidal hormones including androgens. Synthesis of
androgens outside the testes contributes to disease progression in
castration-resistant prostate cancer (CRPC).

Millennium: The Takeda Oncology Company, a leading biopharmaceutical
company based in Cambridge, Mass., markets a first-in-class proteasome
inhibitor and has a robust pipeline of oncology product candidates.
Additional information about Millennium is available through its
website, www.millennium.com.

Located in Osaka, Japan, Takeda is a research-based global company with
its main focus on pharmaceuticals. As the largest pharmaceutical company
in Japan and one of the global leaders of the industry, Takeda is
committed to strive towards better health for patients worldwide through
leading innovation in medicine. Additional information about Takeda is
available through its corporate website, www.takeda.com.

Editor’s Note: This press release is also available under the Media
section at: http://investor.millennium.com/phoenix.zhtml?c=80159&p=irol-newsarticle&....

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Source: Takeda Pharmaceutical Company Limited