MISSISSAUGA, ON, June 16, 2020 – Data from the pre-specified final overall survival (OS) analysis of the Phase III ARAMIS (Androgen Receptor inhibiting Agent for MetastatIc-free Survival) trial has shown NUBEQA^® (darolutamide) plus androgen-deprivation therapy (ADT) significantly improves OS and significantly delays the onset of cancer-associated symptoms, with a comparable safety profile to standard treatment with ADT alone, in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). NUBEQA® is an oral non-steroidal androgen receptor (AR) inhibitor therapy, for the treatment of patients with nmCRPC.

Previously published results from the ARAMIS trial demonstrated a highly significant improvement in the primary efficacy endpoint of metastasis-free survival (MFS), with a median of 40.4 months for darolutamide plus androgen deprivation therapy (ADT) compared to 18.4 months for placebo plus ADT (p<0.001); however, OS data were not yet mature at the time of this analysis.

Highlights of the new and final OS analysis from the ARAMIS trial demonstrated that darolutamide:

• Significantly reduced risk of death by 31 percent (HR=0.69, 95% CI 0.53-0.88; p=0.003) in patients with nmCRPC
• Significantly delayed the time to pain progression, time to first initiation of cytotoxic chemotherapy, and time to first symptomatic skeletal event (SSE)
• Continues to demonstrate a favourable safety profile, with no new safety signals observed, even with a longer treatment duration, allowing men with nmCRPC to maintain their lifestyle quality

“The preplanned final overall survival (OS) analysis of the phase III ARAMIS trial, was just presented during the 2020 ASCO Virtual Meeting,” says Dr. Ricardo Rendon, Professor and Director of Research, Department of Urology Medical Advisory and Research Board, Dalhousie University; Chair, Genitourinary Cancer Site Team; and VP Education, Canadian Urological Association. “After having met its primary metastasis free survival endpoint, darolutamide showed a significant improvement in OS, in addition to delaying the onset of cancer-related complications and the need for subsequent chemotherapy. Darolutamide has low penetration of the blood-brain barrier and in this study, patients receiving darolutamide had no major differences in seizures, dizziness, or cognitive impairment when compared to those patients who received placebo. These results provide compelling evidence for the early use of darolutamide in men with high risk non-metastatic CRPC”

Darolutamide has a distinct chemical structure and inhibits the growth of prostate cancer cells while limiting the burden of side effects on patients’ everyday lives. With extended follow-up, darolutamide’s safety profile remains favourable, allowing patients with nmCRPC to continue their lives without disruption. Consistent with the previously reported primary analysis results, darolutamide plus ADT showed a favourable tolerability confirmed by a longer-term safety analysis compared to ADT alone, without clinically relevant increases in rates of hypertension, falls or central nervous system (CNS) effects. In the follow-up analysis of secondary endpoints, all secondary endpoints were statistically significant. Darolutamide plus ADT significantly delayed time to pain progression, time to first initiation of cytotoxic chemotherapy and time to first symptomatic skeletal event (SSE) versus placebo plus ADT.

NUBEQA^® was approved by Health Canada on February 20, 2020. Canada was the fifth country globally to approve NUBEQA^®, following approvals in the United States, Brazil, Japan, and Australia.

NUBEQA^® recommended for reimbursement in Canada

In April, both the pan-Canadian Oncology Drug Review (pCODR) and the Institut national d’excellence en santé et en services sociaux (INESSS) issued positive recommendations for the reimbursement of NUBEQA^® for the treatment of nmCRPC in patients who are at high risk of developing metastases.^[i],[ii]

The recommendations represent an important step in providing access to treatment for patients suffering from nmCRPC.

"The Canadian Cancer Survivor Network is very pleased that NUBEQA^® has been recommended for prostate cancer patients,” said Jackie Manthorne, President & CEO of the Canadian Cancer Survivor Network (CCSN). “It is important that patients have access to new treatment options to help fill their unmet needs."

"It is very gratifying to have recognized therapeutic treatments for patients at high risk of developing metastases and who need an alternative treatment, as this particular cancer cannot be cured. A message of hope that offers all prostate cancer victims an improvement in their quality of life”, said Laurent Proulx, president and CEO of PROCURE: The Force Against Prostate Cancer. “Despite the current context, it is imperative to continue to support these patients and families by offering them treatments that are not only effective but, above all, within reach thanks to public reimbursement. It is essential that we commit to the negotiation process in each province, because the health and well-being of thousands of patients are at stake. On average, 64 Canadians will be diagnosed with prostate cancer every day, and we must do everything we can to give them access to the best care."

Bayer is pleased that the two Canadian health technology assessment bodies recognized the value of NUBEQA^® and the importance of having another treatment option for nmCRPC patients. As a next step, Bayer looks forward to working with the pan-Canadian pharmaceutical alliance (pCPA) and provincial cancer agencies and drug plans to make NUBEQA^® available to Canadian patients through public coverage in a timely manner. In the interim, Bayer is offering the Darolutamide Access and Reimbursement Touchpoint (DART) patient support program to assist patients prescribed darolutamide with nmCRPC information and access to this therapy.

About darolutamide

Darolutamide is an androgen receptor (AR) inhibitor with a distinct chemical structure that competitively inhibits androgen binding and therefore the growth of prostate cancer cells. Preclinical studies showed that darolutamide has a lower blood-brain barrier penetration compared to other currently available AR inhibitors.^[iii] This is supported by human studies that indicated a low likelihood that darolutamide crosses the intact blood-brain barrier to a clinically relevant extent.^[iv]

The compound is also being investigated in a Phase III study in metastatic hormone-sensitive prostate cancer (ARASENS). Information about these trials can be found at http://www.clinicaltrials.gov.

About castration resistant prostate cancer (CRPC)

In 2019, approximately 22,900 men in Canada were diagnosed with prostate cancer, representing 20% of all new cancer cases in men. Prostate cancer is the most common cancer among Canadian men (excluding non-melanoma skin cancers) and is the third leading cause of death from cancer in men in Canada, resulting in more than 4,100 men deaths annually.^[viii] Prostate cancer results from the abnormal proliferation of cells within the prostate gland, which is part of a man’s reproductive system. Over time, it can progress and spread to other parts of the body, such as lymph nodes and bones. It mainly affects men over the age of 50, and the risk increases with age.

Treatment options range from surgery to radiation treatment to therapy using ADT, substances that stop the formation of testosterone or prevent its effect at the target location. However, in nearly all cases, the cancer eventually becomes resistant to conventional hormone therapy.

CRPC is an advanced form of the disease where the cancer keeps progressing despite ADT treatment, 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. Until two years ago, there had been no treatment options approved by Health Canada for patients who have rising prostate-specific antigen (PSA) levels while on ADT and no detectable metastases, nmCRPC. In patients with progressive nmCRPC, a rapid PSA doubling time has been consistently associated with reduced time to first metastasis and death.

About Oncology at Bayer

Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer in Canada has five marketed products with several other therapies in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.

About Bayer: Science For A Better Life

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 2019, the Group employed around 104,000 people and had sales of 43.5 billion euros. Capital expenditures amounted to 2.9 billion euros, R&D expenses to 5.3 billion euros. For more information, go to www.bayer.ca.

Forward-Looking Statements

This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports, which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

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[i] Darolutamide (Nubeqa) pCODR Expert Review Committee (pERC) Final Recommendation, Available at: https://www.cadth.ca/darolutamide-nubeqa-non-metastatic-castration-resistant-prostate-cancer-details

[ii] Nubeqa, Avis à la Ministre de l'Institut national d’excellence en santé et en services sociaux, Available at: https://www.inesss.qc.ca/fileadmin/doc/INESSS/Inscription_medicaments/Avis_au_ministre/Avril_2020/20200309_AvisMinistre_Web.pdf

[iii] Moilanen A, et al. Sci Rep 2015;5:12007

[iv] NUBEQA® product monograph: https://www.bayer.ca/omr/online/nubeqa-pm-en.pdf