Bayer to Highlight Data from its Expanding Cancer Portfolio at 2020 ASCO GU Cancers Symposium

• New data to be presented on the effect of Nubeqa^® (darolutamide) on cerebral blood flow in men with non-metastatic castration-resistant prostate cancer (nmCRPC)
• Presentations feature data on Xofigo^® (radium Ra 223 dichloride), including real-world analyses and investigational combination therapies in men with certain types of prostate cancer

Abstracts: 326, TPS384, 130, 32, 50, 56, 125, 89, 59, 136, 223, 236

WHIPPANY, N.J.–(BUSINESS WIRE)–Bayer announced today data from the Company’s evolving oncology portfolio will be presented at the 2020 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, taking place February 13-15, 2020 in San Francisco, California. The presentations across the latest research for Bayer’s marketed and pipeline therapies highlight the company’s ongoing commitment to exploring the potential of its therapies across different indications and treatment settings.

New data on the effect of Nubeqa^® (darolutamide) on cerebral blood flow compared to enzalutamide in men with non-metastatic castration-resistant prostate cancer (nmCRPC) will be presented. Nubeqa, an androgen receptor inhibitor (ARi) jointly developed by Bayer and Orion Corporation, is approved in the U.S., Japan and Brazil, and recently received a positive CHMP opinion in the European Union (EU).

The research presented from Bayer’s prostate cancer portfolio will also include several presentations that feature real-world and combination studies with Xofigo^® (radium Ra 223 dichloride) in men with certain types of prostate cancer. Among these is the first presentation of investigational data from a randomized Phase II study of sipuleucel-T (SipT) with or without Xofigo in men with asymptomatic metastatic castration-resistant prostate cancer (mCRPC).

Notable presentations at ASCO GU 2020 are listed below:

Darolutamide

• Analysis of cerebral blood flow (CBF) in regions relevant to cognitive function with enzalutamide (ENZA) compared to darolutamide (DARO) and placebo (PBO) in healthy volunteers
  • Abstract: 326, Poster Session A: Prostate Cancer; Board M10
  • February 13, 11:30am – 1:00pm, 5:30 – 6:30pm (PST)
• INTREPId (INTermediate Risk Erection PreservatIon Trial): A randomized trial of radiation therapy and darolutamide for prostate cancer
  • Abstract: TPS384, Trials in Progress Poster Session A: Prostate Cancer; Board Q4
  • February 13, 11:30am – 1:00pm, 5:30 – 6:30pm (PST)

Radium Ra 223 Dichloride (radium-223)

• Randomized phase II study of sipuleucel-T (SipT) with or without radium-223 (Ra223) in men with asymptomatic bone-metastatic castrate-resistant prostate cancer (mCRPC) – Investigator initiated research (IIR)
  • Abstract: 130, Poster Session A: Prostate Cancer; Board F10
  • February 13, 11:30am – 1:00pm, 5:30 – 6:30pm (PST)
• Clinical outcomes and patient (pt) profiles in REASSURE: An observational study of radium-223 (Ra-223) in metastatic castration-resistant prostate cancer (mCRPC)
  • Abstract: 32, Poster Session A: Prostate Cancer; Board A20
  • February 13, 11:30am – 1:00pm, 5:30 – 6:30pm (PST)
• Concurrent or layered treatment (Tx) with radium-223 (Ra-223) and enzalutamide (Enza) or abiraterone plus prednisone/prednisolone (Abi/pred): a retrospective study of real-world clinical outcomes in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)
  • Abstract: 50, Poster Session A: Prostate Cancer; Board B16
  • February 13, 11:30am – 1:00pm, 5:30 – 6:30pm (PST)
• Variance in symptom assessment between patient and caregiver: a prospective study of patients staged as metastatic prostate cancer — an interim analysis – IIR
  • Abstract: 56, Poster Session A: Prostate Cancer; Board B22
  • February 13, 11:30am – 1:00pm, 5:30 – 6:30pm (PST)
• Randomized phase II trial of radium-223 (RA) plus enzalutamide (EZ) versus EZ alone in metastatic castration-refractory prostate cancer (mCRPC): Long-term follow up of secondary endpoints – IIR
  • Abstract: 125, Poster Session A: Prostate Cancer; Board F5
  • February 13, 11:30am – 1:00pm, 5:30 – 6:30pm (PST)
• PRINT: Prostate Cancer Intensive, Non-Cross Reactive Therapy for CRPC — Early Observations of Efficacy – IIR
  • Abstract: 89, Poster Session A: Prostate Cancer; Board D13
  • February 13, 11:30am – 1:00pm, 5:30 – 6:30pm (PST)
• The National Radium-223 Dichloride Audit Group: data from patients in United Kingdom oncology centers with metastatic castration-resistant prostate cancer treated with radium-223 dichloride – IIR
  • Abstract: 59, Poster Session A: Prostate Cancer; Board C3
  • February 13, 11:30am – 1:00pm, 5:30 – 6:30pm (PST)
• Results of the ADRRAD Trial of pelvic IMRT plus radium-223 in men with mHSPC metastatic to bone – IIR
  • Abstract: 136, Poster Session A: Prostate Cancer; Board F16
  • February 13, 11:30am – 1:00pm, 5:30 – 6:30pm (PST)
• Real-world utilization of radium-223 (Ra-223) for the treatment of metastatic castration resistant prostate cancer (mCRPC): a U.S. tertiary oncology center analysis
  • Abstract: 223, Poster Session B: Prostate Cancer; Urothelial Carcinoma; Penile, Urethral, Testicular, and Adrenal Cancers; Board B1
  • February 14, 12:15 – 1:45pm, 5:15 – 6:15pm (PST)
• Safety and effectiveness of radium-223 dichloride (Ra-223) in patients with mCRPC in real-world setting: A Japanese post-marketing study (PMS)
  • Abstract: 236, Poster Session B: Prostate Cancer; Urothelial Carcinoma; Penile, Urethral, Testicular, and Adrenal Cancers; Board B14
  • February 14, 12:15 – 1:45pm, 5:15 – 6:15pm (PST)

About NUBEQA^® (darolutamide)¹

NUBEQA is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription.¹ A Phase III study in metastatic hormone-sensitive prostate cancer (ARASENS) is ongoing. Information about this trial can be found at www.clinicaltrials.gov.

On July 30th, 2019, the FDA approved NUBEQA^® (darolutamide) based on the ARAMIS trial, a randomized, double-blind, placebo-controlled, multi-center Phase III study, which evaluated the safety and efficacy of oral NUBEQA in patients with nmCRPC who were receiving a concomitant gonadotropin-releasing hormone (GnRH) analog or had a bilateral orchiectomy. In the clinical study, 1,509 patients were randomized in a 2:1 ratio to receive 600 mg of NUBEQA orally twice daily or placebo plus ADT. The primary efficacy endpoint was MFS, defined as the time from randomization to the time of first evidence of blinded independent central review (BICR)-confirmed distant metastasis or death due to any cause within 33 weeks after the last evaluable scan, whichever occurred first. NUBEQA plus ADT demonstrated a statistically significant improvement in MFS, with a median MFS of 40.4 months [95% CI (34.3, NR), p<0.0001] versus 18.4 months [95% CI (15.5, 22.3), p<0.0001] with placebo plus ADT [HR=0.41, 95% CI (0.34, 0.50), p<0.0001].

Adverse reactions occurring more frequently in the NUBEQA arm (≥2 % over placebo) were fatigue (16% versus 11%), pain in extremity (6% versus 3%) and rash (3% versus 1%). NUBEQA was not studied in women and there is a warning and precaution for embryo-fetal toxicity.

Overall survival (OS) data were not mature at the time of final MFS analysis (57% of the required number of events). The planned final analysis has been conducted and mature data on OS and other secondary endpoints will be presented at an upcoming scientific meeting.

INDICATION for NUBEQA (darolutamide)

NUBEQA is approved for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC).¹

IMPORTANT SAFETY INFORMATION for NUBEQA (darolutamide)

Embryo-Fetal Toxicity: Safety and efficacy of NUBEQA have not been established in females. NUBEQA can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment with NUBEQA and for 1 week after the last dose.

Adverse Reactions

Adverse reactions occurring more frequently in the NUBEQA arm (≥2% over placebo) were fatigue (16% vs. 11%), pain in extremity (6% vs. 3%) and rash (3% vs. 1%). Serious adverse reactions occurred in 25% of patients receiving NUBEQA and in 20% of patients receiving placebo. Serious adverse reactions in ≥ 1 % of patients who received NUBEQA were urinary retention, pneumonia, and hematuria. Overall, 3.9% of patients receiving NUBEQA and 3.2% of patients receiving placebo died from adverse reactions, which included death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%) for NUBEQA. Clinically significant adverse reactions occurring in ≥ 2% of patients treated with NUBEQA included ischemic heart disease (4.0% vs. 3.4% on placebo) and heart failure (2.1% vs. 0.9% on placebo).

Drug Interactions

Effect of Other Drugs on NUBEQA –Concomitant use of NUBEQA with a combined P-gp and strong or moderate CYP3A4 inducer decreases darolutamide exposure, which may decrease NUBEQA activity. Avoid concomitant use of NUBEQA with combined P-gp and strong or moderate CYP3A4 inducers.

Concomitant use of NUBEQA with a combined P-gp and strong CYP3A4 inhibitor increases darolutamide exposure, which may increase the risk of NUBEQA adverse reactions. Monitor patients more frequently for NUBEQA adverse reactions and modify NUBEQA dosage as needed.

Effects of NUBEQA on Other Drugs –NUBEQA is an inhibitor of breast cancer resistance protein (BCRP) transporter. Concomitant use of NUBEQA increases the exposure (AUC) and maximal concentration of BCRP substrates, which may increase the risk of BCRP substrate-related toxicities. Avoid concomitant use with drugs that are BCRP substrates where possible. If used together, monitor patients more frequently for adverse reactions, and consider dose reduction of the BCRP substrate drug. Consult the approved product labeling of the BCRP substrate when used concomitantly with NUBEQA.

For important risk and use information about NUBEQA, please see the accompanying full Prescribing Information.

About Xofigo^® (radium Ra 223 dichloride) Injection²

Xofigo is indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease.

Important Safety Information for Xofigo^® (radium Ra 223 dichloride) Injection

Warnings and Precautions:

• Bone Marrow Suppression: In the phase 3 ALSYMPCA trial, 2% of patients in the Xofigo arm experienced bone marrow failure or ongoing pancytopenia, compared to no patients treated with placebo. There were two deaths due to bone marrow failure. For 7 of 13 patients treated with Xofigo bone marrow failure was ongoing at the time of death. Among the 13 patients who experienced bone marrow failure, 54% required blood transfusions. Four percent (4%) of patients in the Xofigo arm and 2% in the placebo arm permanently discontinued therapy due to bone marrow suppression. In the randomized trial, deaths related to vascular hemorrhage in association with myelosuppression were observed in 1% of Xofigo-treated patients compared to 0.3% of patients treated with placebo. The incidence of infection-related deaths (2%), serious infections (10%), and febrile neutropenia (<1%) was similar for patients treated with Xofigo and placebo. Myelosuppression–notably thrombocytopenia, neutropenia, pancytopenia, and leukopenia–has been reported in patients treated with Xofigo.

  Monitor patients with evidence of compromised bone marrow reserve closely and provide supportive care measures when clinically indicated. Discontinue Xofigo in patients who experience life-threatening complications despite supportive care for bone marrow failure

• Hematological Evaluation: Monitor blood counts at baseline and prior to every dose of Xofigo. Prior to first administering Xofigo, the absolute neutrophil count (ANC) should be ≥1.5 × 10⁹/L, the platelet count ≥100 × 10⁹/L, and hemoglobin ≥10 g/dL. Prior to subsequent administrations, the ANC should be ≥1 × 10⁹/L and the platelet count ≥50 × 10⁹/L. Discontinue Xofigo if hematologic values do not recover within 6 to 8 weeks after the last administration despite receiving supportive care

• Concomitant Use With Chemotherapy: Safety and efficacy of concomitant chemotherapy with Xofigo have not been established. Outside of a clinical trial, concomitant use of Xofigo in patients on chemotherapy is not recommended due to the potential for additive myelosuppression. If chemotherapy, other systemic radioisotopes, or hemibody external radiotherapy are administered during the treatment period, Xofigo should be discontinued

• Increased Fractures and Mortality in Combination With Abiraterone Plus Prednisone/Prednisolone: Xofigo is not recommended for use in combination with abiraterone acetate plus prednisone/prednisolone outside of clinical trials. At the primary analysis of the Phase 3 ERA-223 study that evaluated concurrent initiation of Xofigo in combination with abiraterone acetate plus prednisone/prednisolone in 806 asymptomatic or mildly symptomatic mCRPC patients, an increased incidence of fractures (28.6% vs 11.4%) and deaths (38.5% vs 35.5%) have been observed in patients who received Xofigo in combination with abiraterone acetate plus prednisone/prednisolone compared to patients who received placebo in combination with abiraterone acetate plus prednisone/prednisolone. Safety and efficacy with the combination of Xofigo and agents other than gonadotropin-releasing hormone analogues have not been established

• Embryo-Fetal Toxicity: The safety and efficacy of Xofigo have not been established in females. Xofigo can cause fetal harm when administered to a pregnant female. Advise pregnant females and females of reproductive potential of the potential risk to a fetus. Advise male patients to use condoms and their female partners of reproductive potential to use effective contraception during and for 6 months after completing treatment with Xofigo

Administration and Radiation Protection: Xofigo should be received, used, and administered only by authorized persons in designated clinical settings. The administration of Xofigo is associated with potential risks to other persons from radiation or contamination from spills of bodily fluids such as urine, feces, or vomit. Therefore, radiation protection precautions must be taken in accordance with national and local regulations

Fluid Status: Dehydration occurred in 3% of patients on Xofigo and 1% of patients on placebo. Xofigo increases adverse reactions such as diarrhea, nausea, and vomiting, which may result in dehydration. Monitor patients’ oral intake and fluid status carefully and promptly treat patients who display signs or symptoms of dehydration or hypovolemia

Injection Site Reactions: Erythema, pain, and edema at the injection site were reported in 1% of patients on Xofigo

Secondary Malignant Neoplasms: Xofigo contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure may be associated with an increased risk of cancer and hereditary defects. Due to its mechanism of action and neoplastic changes, including osteosarcomas, in rats following administration of radium-223 dichloride, Xofigo may increase the risk of osteosarcoma or other secondary malignant neoplasms. However, the overall incidence of new malignancies in the randomized trial was lower on the Xofigo arm compared to placebo (<1% vs 2%; respectively), but the expected latency period for the development of secondary malignancies exceeds the duration of follow-up for patients on the trial

Subsequent Treatment With Cytotoxic Chemotherapy: In the randomized clinical trial, 16% of patients in the Xofigo group and 18% of patients in the placebo group received cytotoxic chemotherapy after completion of study treatments. Adequate safety monitoring and laboratory testing was not performed to assess how patients treated with Xofigo will tolerate subsequent cytotoxic chemotherapy

Adverse Reactions: The most common adverse reactions (≥10%) in the Xofigo arm vs the placebo arm, respectively, were nausea (36% vs 35%), diarrhea (25% vs 15%), vomiting (19% vs 14%), and peripheral edema (13% vs 10%). Grade 3 and 4 adverse events were reported in 57% of Xofigo-treated patients and 63% of placebo-treated patients. The most common hematologic laboratory abnormalities in the Xofigo arm (≥10%) vs the placebo arm, respectively, were anemia (93% vs 88%), lymphocytopenia (72% vs 53%), leukopenia (35% vs 10%), thrombocytopenia (31% vs 22%), and neutropenia (18% vs 5%)

Please see the full Prescribing Information for Xofigo (radium Ra 223 dichloride).

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 now expands to six marketed products and several other assets 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

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

^© 2020 Bayer

BAYER, the Bayer Cross, Nubeqa and Xofigo are registered trademarks of Bayer.

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.

References

1. Nubeqa^® (darolutamide) tablets [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, July 2019.
2. XOFIGO^® (radium-223 dichloride) Injection [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, December 2019.

PP-PF-ONC-US-1081-1 02/20

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