American Society of Clinical Oncology Ge nitourinary Cancers Symposium (ASCO GU) 2019

Bayer’s darolutamide plus androgen deprivation therapy (ADT) significantly extends metastasis-free survival with a favorable
safety profile compared to placebo plus ADT in non-metastatic castration-resistant prostate cancer

  • Statistically significant improvement in metastasis-free survival (MFS), with a median MFS of 40.4 months with darolutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT (18.4 months)

  • Positive trend in overall survival with a 29% reduction in risk of death at interim analysis (P=0.045)

  • Incidence of treatment-emergent adverse events was similar for darolutamide plus ADT and placebo plus ADT

  • Health-related quality of life was maintained

  • First results from the Phase III ARAMIS trial with the androgen receptor antagonist darolutamide were presented in an oral pres entation at American Society of Clinical Oncology Genitourinary Cancers Symposium and simultaneously published in The New England Journal of Medicine



Results from the pivotal Phase III ARAMIS trial in patients
with non-metastatic castration-resistant prostate cancer (nmCRPC) showed a statistically
significant improvement in metastasis-free survival (MFS) with darolutamide plus
androgen deprivation therapy (ADT) compared to placebo plus ADT (HR=0.41, 95% CI
0.34-0.50; P<0.001). This translates to a 59 percent reduction in the risk of metastasis or death.

The median MFS was 40.4 months in the darolutamide arm compared with 18.4
months for the placebo arm – an overall improvement in median MFS of 22 months.
A positive trend in overall survival (OS) was also observed (HR=0.71, 95% CI 0.50-0.99;
P=0.045), and all other secondary endpoints demonstrated a benefit in favor of
darolutamide. Importantly, the incidence of treatment-emergent adverse events (AEs) with
greater than or equal to 5 percent frequency or of grade 3–5 was comparable between
darolutamide and placebo arms; only fatigue occurred in more than 10 percent of patients
(darolutamide plus ADT resulted in 12.1 percent versus 8.7 percent in patients with
placebo plus ADT). Quality of life outcomes were similar between the treatment groups.
These data were presented at the American Society of Clinical Oncology Genitourinary
Cancers Symposium (ASCO GU) in San Francisco and published simultaneously in The
New England Journal of Medicine.

“In addition to a benefit in MFS, a favorable safety profile is critical for these largely
asymptomatic nmCRPC patients because treatment decisions can impact their overall
well-being, prognosis and compliance with the treatment as well as other medications that
are typical for this patient population. These data are exciting for the prostate cancer
community; they not only show darolutamide’s significant efficacy in preventing the
spread of prostate cancer, but also its favorable tolerability profile that, once approved,
may allow patients to continue their day-to-day life without adding any burden,” said Karim
Fizazi, M.D., Ph.D., Professor of Medicine at the Institut Gustave Roussy, University of
Paris Sud, France.

“While many new treatment options in the field of prostate cancer have been developed in
recent years, gaps persist, particularly in providing patients with treatments that are both
effective and have a safety profile that does not constitute an additional toxicity burden in
their lives,” said Scott Z. Fields, M.D., senior vice president and head of Oncology
Development at Bayer's Pharmaceutical Division. “Bayer is working diligently to bring
innovative, efficacious and tolerable treatments to patients in need. With the positive
results of the ARAMIS trial, we are one step closer to our goal of bringing darolutamide to
patients and physicians.”

Bayer plans to discuss the data from the ARAMIS trial with health authorities regarding
the submission of new drug applications. Bayer has been granted Fast Track designation

by the U.S. Food and Drug Administration (FDA) for darolutamide in men with nmCRPC.
Darolutamide is being developed jointly by Bayer and Orion Corporation, a globally
operating Finnish pharmaceutical company.

Detailed study results

The MFS benefit observed with darolutamide was consistent across all subgroups of
patients. In an interim analysis of OS, darolutamide showed a positive trend, with a
29 percent reduction in the risk of death (HR=0.71, 95% CI 0.50-0.99; P=0.045, median
not reached).

In addition, darolutamide plus ADT demonstrated a significant benefit over placebo plus
ADT for time to pain progression (40.3 months compared to 25.4 months; HR=0.65, 95%
CI 0.53-0.79; P<0.001) and time to cytotoxic chemotherapy (median not reached
compared to 38.2; HR=0.43, 95% CI 0.31-0.60; P<0.001). Another secondary endpoint,
time to first symptomatic skeletal event (SSE), also demonstrated a benefit in favor of
darolutamide (median not reached). Darolutamide extended progression-free survival
(PFS) (36.8 months compared to 14.8 months; HR=0.38, 95% CI 0.32-0.45; P<0.001),
with a 62 percent risk reduction of local progression, distant metastases or death.

Incidence of treatment-emergent AEs was similar between darolutamide and placebo;
most AEs were grade 1 and 2 (55 percent with darolutamide plus ADT and 54 percent
with placebo plus ADT). Compared to placebo plus ADT, darolutamide plus ADT did not
increase rates of critical AEs including, but not limited to, seizures, falls, fractures, rash,
cognitive disorder, mental impairment or hypertension. Patients with a history of seizure
were not excluded from the study.

The results of Patient Reported Outcomes (PRO)-based endpoints (based on the
Functional Assessment of Cancer Therapy-Prostate; FACT-P, European Organisation for
Research and Treatment of Cancer quality of life; EORTC-QLQ-PR25, and EQ-5D-3L
questionnaires) demonstrated maintenance of health-related quality of life (HRQoL) with a
positive trend favoring darolutamide over placebo.