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2019 American Society of Clinical Oncology (ASCO) Annual Meeting - Darolutamide data presented

31.05.2019 klo 17:00 2019 American Society of Clinical Oncology (ASCO) Annual Meeting - Darolutamide data presented



Orion Corporation                  Press release                         31 May
2019 at 5.00 p.m.  EEST


2019 American Society of Clinical Oncology (ASCO) Annual Meeting - Darolutamide
data presented

Orion's and Bayer's darolutamide plus androgen deprivation therapy (ADT) delays
worsening of disease-related symptoms and maintains quality of life beyond end
of study treatment compared to placebo plus ADT in men with non-metastatic
castration-resistant prostate cancer.

  * Results of a new post-hoc analysis showed that treatment with darolutamide
    plus androgen deprivation therapy (ADT) delayed worsening of urinary and
    bowel symptoms versus placebo plus ADT(1

    )
  * Exposure adjusted incidences of treatment-emergent adverse events (TEAEs),
    including notably TEAEs associated with androgen receptor (AR) antagonists,
    were similar for darolutamide plus ADT compared to placebo plus ADT(1

    )
  * Darolutamide plus ADT maintained quality of life in men with non-metastatic
    castration-resistant prostate cancer (nmCRPC) beyond end of study treatment
    with scores similar to placebo plus ADT(1

    )
  * Analysis on quality of life related endpoints from pivotal Phase III ARAMIS
    trial presented at the American Society of Clinical Oncology (ASCO) as an
    oral presentation on May 31, 2019

  * Darolutamide is under Priority Review in the U.S., and has been filed in
    Europe, Japan and additional countries

Abstract 5000
Darolutamide plus androgen deprivation therapy (ADT) delays worsening of
disease-related symptoms in men with non-metastatic castration-resistant
prostate cancer (nmCRPC) compared with placebo plus ADT, according to
exploratory data from the pivotal Phase III ARAMIS trial presented in an oral
presentation at the American Society of Clinical Oncology (ASCO) Annual
Meeting in Chicago. Exposure-adjusted incidences of treatment-emergent adverse
events (TEAEs), including notably TEAEs associated with androgen receptor (AR)
antagonists, were generally similar for darolutamide plus ADT compared to
placebo plus ADT(1). Data also indicate that darolutamide plus ADT maintained
quality of life, compared to placebo plus ADT even beyond the end of study
treatment. Primary results of this study have been previously published in the
New England Journal of Medicine.(3) Based on the study results, the U.S. Food
and Drug Administration (FDA) granted Priority Review for the New Drug
Application (NDA) for darolutamide in April 2019, and Bayer has filed for
approval in the European Union (EU), Japan, as well as other health authorities.
Darolutamide is being developed jointly by Orion Corporation and Bayer.

"At this stage of prostate cancer, when men typically feel well and generally do
not have symptoms, it is important that we have potential treatment options that
will prevent the spread of prostate cancer for as long as possible, while
limiting burdensome side effects of therapy, which allows patients to continue
their day-to-day lives," said Karim Fizazi, M.D., Ph.D., Professor of Medicine
at the Institut Gustave Roussy, University of Paris Sud, France. "These new data
demonstrate darolutamide's ability to maintain patients' quality of life while
receiving treatment. When you add these findings to previously reported data,
the product has the potential to become an important treatment option for men
with nmCRPC."

"The results from the ARAMIS trial published recently in the New England Journal
of Medicine showed that Darolutamide is highly effective in the treatment of
patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and
that darolutamide has an excellent safety profile that resembles that of
placebo. The new analyses from the ARAMIS trial show that patients treated with
Darolutamide maintain their quality of life while on Darolutamide treatment,
which is very good news for the patients. These highly important results
encourage us further to bring this treatment to nmCRPC patients as soon as
possible," said Christer Nordstedt, MD, PhD, Senior Vice President, Research and
Development, Orion Corporation.

Darolutamide data presented at ASCO
In an analysis focusing on patient-relevant endpoints, data on the secondary
endpoint of time to pain progression, assessed by the BPI-SF (Brief Pain
Inventory - Short Form) patient questionnaire, show that darolutamide plus ADT
delayed worsening of pain in men with nmCRPC versus placebo plus ADT (40.3
versus 25.4 months; HR 0.65; 95% CI 0.53-0.79; P<0.001).(1) At this interim
analysis, the results are not statistical significant.(1)

In a pre-planned analysis on the FACT-P PCS (Functional Assessment of Cancer
Therapy - Prostate, Prostate Cancer Subscale) questionnaire, quality of life was
maintained in men receiving treatment with darolutamide plus ADT, as
demonstrated by mean scores from the FACT-P PCS.(1) FACT-P PCS assesses both
impact of disease- and treatment related symptoms on men's quality of life, and
was assessed every 16 weeks until end of study treatment, and at every visit
thereafter until end of study or death.(1) Mean scores were maintained and
similar in both treatment arms throughout the study. At the end of treatment,
the mean change from baseline of -8.55 with darolutamide plus ADT was similar to
placebo plus ADT.(1) The quality of life scores were maintained beyond end of
study treatment.

A new post-hoc analysis of the ARAMIS data shows that treatment with
darolutamide plus ADT delays the onset of urinary and bowel symptoms in men with
nmCRPC compared to placebo plus ADT (urinary symptoms: 25.8 versus 4.8 months;
HR=0.64; 95% CI 0.54-0.76; P<0.01; bowel symptoms: 18.4 versus 11.5 months;
HR=0.78; 95% CI 0.66-0.92; P<0.01), as shown by time to deterioration of
symptoms in the European Organisation for Research and Treatment of Cancer QoL
Prostate Cancer module (EORTC-QLQ-PR25).(1) Statistical significance cannot be
reported as these are exploratory endpoint data.(1)

Exposure-adjusted incidences of treatment-emergent adverse events (TEAEs),
including notably TEAEs associated with androgen receptor (AR) antagonists, were
generally similar for darolutamide plus ADT compared to placebo plus ADTand
included fatigue/asthenic conditions (11.3% versus 11.1%), hypertension (4.7%
versus 5.1%), falls (3.0% versus 4.6%), cognitive disorder (0.3% versus 0.2%),
and memory impairment (0.4% versus 1.2%) .(1)

About the ARAMIS trial
The ARAMIS trial is a randomized, Phase III, multi-center, double-blind,
placebo-controlled trial evaluating the safety and efficacy of oral darolutamide
in patients with nmCRPC who are currently being treated with androgen
deprivation therapy (ADT) as standard of care and are at high risk for
developing metastatic disease. 1,509 patients were randomized in a 2:1 ratio to
receive 600 mg of darolutamide twice a day or placebo along with ADT.

About darolutamide
Darolutamide is a non-steroidal androgen receptor (AR) antagonist with a
distinct chemical structure that binds to the receptor with high affinity and
exhibits strong antagonistic activity, thereby inhibiting the receptor function
and the growth of prostate cancer cells. In preclinical studies, darolutamide
demonstrated lower blood-brain barrier penetration compared to other currently
available AR antagonists.(4)

In addition to the Phase III ARAMIS trial in men with nmCRPC, darolutamide is
also being investigated in a Phase III study in metastatic hormone-sensitive
prostate cancer (ARASENS). Information about these trials can be found
at www.clinicaltrials.gov.

Darolutamide is not approved by the U.S. FDA, the European Medicines Agency or
any other health authority.

About castration-resistant prostate cancer (CRPC)
Prostate cancer is the second most commonly diagnosed malignancy in men
worldwide.(5) In 2018, an estimated 1.2 million men were diagnosed with prostate
cancer, and about 358,000 died from the disease worldwide.(5) Prostate cancer is
the fifth leading cause of death from cancer in men.(5) Prostate cancer results
from the abnormal proliferation of cells within the prostate gland, which is
part of a man's reproductive system.(6) It mainly affects men over the age of
50, and the risk increases with age.(7) Treatment options range from surgery to
radiation treatment to therapy using hormone-receptor antagonists, i.e.,
substances that stop the formation of testosterone or prevent its effect at the
target location.(8) However, in nearly all cases, the cancer eventually becomes
resistant to conventional hormone therapy.(9)


CRPC is an advanced form of the disease where the cancer keeps progressing even
when the amount of testosterone is reduced to very low levels in the body. The
field of treatment options for castration-resistant patients is evolving
rapidly, but until recently, there have been no effective treatment options for
CRPC patients who have rising prostate-specific antigen (PSA) levels while on
ADT and no detectable metastases. In men with progressive nmCRPC, a rapid PSA
doubling time has been consistently associated with reduced time to first
metastasis and death.(10)




About Orion
Orion is a globally operating Finnish pharmaceutical company - a builder of
well-being. Orion develops, manufactures and markets human and veterinary
pharmaceuticals and active pharmaceutical ingredients. The company is
continuously developing new drugs and treatment methods. The core therapy areas
of Orion's pharmaceutical R&D are central nervous system (CNS) disorders,
oncology and respiratory diseases for which Orion develops inhaled Easyhaler®
pulmonary drugs. Orion's net sales in 2018 amounted to EUR 977 million and the
company had about 3,200 employees at the end of the year. Orion's A and B shares
are listed on Nasdaq Helsinki.


About Bayer
Bayer is a global enterprise with core competencies in the life science fields
of health care and nutrition. Its products and services are designed to benefit
people by supporting efforts to overcome the major challenges presented by a
growing and aging global population. At the same time, the Group aims to
increase its earning power and create value through innovation and growth. Bayer
is committed to the principles of sustainable development, and the Bayer brand
stands for trust, reliability and quality throughout the world. In fiscal 2018,
the Group employed around 117,000 people and had sales of 39.6 billion euros.
Capital expenditures amounted to 2.6 billion euros, R&D expenses to 5.2 billion
euros. For more information, go to www.bayer.com.



Contact persons:


Christer Nordstedt, MD, PhD, Senior Vice President, Research and Development,
Orion Corporation
Tel. +358 10 426 2099
christer.nordstedt@orion.fi



Media Contacts:


Terhi Ormio
Vice President, Communications, Orion Corporation
Tel. +358 (0)50 966 4646
terhi.ormio@orion.fi







References

 1. Fizazi, Karim; Shore, Neal; Tammela, Teuvo, et al. Impact of darolutamide
    (DARO) on pain and quality of life (QoL) in patients (Pts) with
    nonmetastatic castrate-resistant prostate cancer (nmCRPC). American Society
    of Clinical Oncology Annual Meeting 2019; May 31, 2019; Chicago, IL.
    Abstract 5000.
 2. Fizazi, Karim; Shore, Neal; Tammela, Teuvo, et al. Darolutamide in
    Nonmetastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2019; doi:
    10.1056/NEJMoa1815671.
 3. Moilanen, Anu-Maarit; Riikonen, Reetta; Oksala, Riikka, et al. Discovery of
    ODM-201, a new-generation androgen receptor inhibitor targeting resistance
    mechanisms to androgen signaling-directed prostate cancer therapies. Sci
    Rep. 2015;5:12007
 4. GLOBOCAN 2018: Estimated Cancer Incidence, Mortality and Prevalence
    Worldwide in 2018. Prostate Cancer.
    https://onlinelibrary.wiley.com/doi/epdf/10.3322/caac.21492. Accessed May
    2019.
 5. American Cancer Society. What is Prostate Cancer?
    https://www.cancer.org/content/dam/CRC/PDF/Public/8793.00.pdf. Accessed May
    2019.
 6. American Cancer Society. Prostate Cancer Risk Factors.
    https://www.cancer.org/content/dam/CRC/PDF/Public/8794.00.pdf. Accessed May
    2019.
 7. National Cancer Institute. Hormone Therapy for Prostate Cancer.
    https://www.cancer.gov/types/prostate/prostate-hormone-therapy-fact-sheet.
    Accessed May 2019.
 8. Nakazawa, Mary; Paller, Channing; Kyprianou, Natasha.  Mechanisms of
    Therapeutic Resistance in Prostate Cancer. Curr Oncol Rep (2017) 19:13.
 9. Howard, Lauren; Moreira, Daniel M; DeHoedt, Amanda; Aronson, William J., et
    al.  Thresholds for PSA doubling time in men with non-metastatic castration-
    resistant prostate cancer. BJU Int 2017;120: E80-E86.




Publisher:
Orion Corporation
Communications
Orionintie 1A, FI-02200 Espoo, Finland



Orion is a globally operating Finnish pharmaceutical company - a builder of
well-being. Orion develops, manufactures and markets human and veterinary
pharmaceuticals and active pharmaceutical ingredients. The company is
continuously developing new drugs and treatment methods. The core therapy areas
of Orion's pharmaceutical R&D are central nervous system (CNS) disorders,
oncology and respiratory diseases for which Orion develops inhaled Easyhaler®
pulmonary drugs. Orion's net sales in 2018 amounted to EUR 977 million and the
company had about 3,200 employees at the end of the year. Orion's A and B shares
are listed on Nasdaq Helsinki. For more information, go to www.orion.fi/en



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