Darolutamide

Treating patients with high-risk localized or locally advanced prostate cancer with Erleada and hormone therapy before and after surgery extended the time before patients would need subsequent therapy by six years, J&J found in its Proteus study. With a new phase 3 win for Erleada (apalutamide), Johnson & Johnson is proposing a solution to a longstanding prostate cancer treatment gap.For patients with high-risk localized or locally advanced prostate cancer, surgical removal of the prostate (radical prostatectomy) is a key standard treatment alongside radiation therapy. But nearly half of patients who move forward with curative-intent surgery ultimately see their cancer return, requiring additional treatment and potentially missing the window in which a cure is possible.  Additional therapies often intervene only after the cancer has spread, limiting the chance to improve long-term outcomes. This has been the status quo essentially since the prostatectomy was introduced 125 years ago in 1904, J&J’s U.S. president of oncology for solid tumors, Biljana Naumovic, M.D., told Fierce in an interview on the sidelines of the 2026 American Society of Clinical Oncology (ASCO) annual meeting. With its phase 3 Proteus study, J&J sought a solution—a way to meet the “one chance for curing this patient,” Mark Wildgust, Ph.D., J&J’s VP of global medical affairs for oncology, said in the joint interview. In Proteus, when Erleada was given to patients with high-risk localized or locally advanced disease alongside hormone therapy (androgen deprivation therapy or ADT) for six months before and after surgery, the drug was able to provide significant improvements in “key short- and long-term clinical outcomes,” the company said in a May 31 release. Patients who used Erleada and hormone therapy were nine times more likely to have “little to no” cancer remaining at the time of surgery compared with those on hormone therapy alone, with the treatment arm linked to a 8.9% rate of pathologic complete response/minimal residual disease compared to 1% among the hormone therapy-only group, the company said.The regimen also reduced the risk of developing metastasis or death by 20% and extended the time before patients required additional therapy to more than six years, J&J reported. That latter figure nearly doubled the three and a half years experienced by those on hormone therapy alone. This result is “most impactful,” as it “may reduce the need for subsequent therapies and related side effects, while also increasing potential cure rates,” principal trial investigator Mary-Ellen Taplin, Ph.D., of Dana-Farber Cancer Institute and Harvard Medical School, commented in the release. “This approach, which combines systemic therapy with surgery, is already standard in other aggressive cancers and now has proven benefit in patients with this disease.” The findings were unveiled at a plenary session at ASCO and simultaneously published in the New England Journal of Medicine. Inclusion in the plenary is no small feat, as it represents ASCO “heralding that we are seeing a fundamental change in how we have treated these patients,” Wildgust said. The decades-long treatment gap Erleada could potentially fill has been well-known, but until now, “nobody had the audacity” to run a phase 3, 2,000-patient study in the space, according to the exec. “We had the conviction that Erleada is different,” Wildgust said. Additional analyses from the Proteus study, such as “ongoing evaluations” stacking up the regimen against surgery alone, are in the works to “further contextualize these findings,” according to J&J. “Apalutamide has already shown an overall survival benefit in advanced disease. Now we’re seeing its impact when used earlier, alongside surgery,” Yusri Elsayed, M.D., Ph.D., J&J’s global therapeutic area head for oncology, noted in the release. “As the first therapy in its class to show benefit in this setting, these data reinforce apalutamide’s differentiated profile and the need to move beyond a surgery-only approach to treating earlier and improving long-term outcomes.”The company figures that adding Erleada to the existing treatment approach could work well because in real-world practice, patients schedule surgeries weeks ahead of time. “Instead of waiting for six to eight weeks, you actually give them treatment right away, and then after six months you schedule the surgery and the results are incredible,” Naumovic explained. About 330,000 people in the U.S. are diagnosed with prostate cancer each year, with up to 40% classified as high-risk. More than 36,000 patients are estimated to succumb to their disease this year, which “reinforces the importance of choosing the best possible therapy early,” the company emphasized.Erleada sits in the androgen receptor inhibitor drug class that many of its competitors, such as Bayer’s Nubeqa and Pfizer’s Astellas-partnered Xtandi, also occupy. But Erleada, Wildgust said, is “differentiated” and “unique,” rejecting the notion that the drugs are “all kind of interchangeable.”This has also been proven by head-to-head analyses against others in the drug class, such as February’s data set in which J&J used real-world data to pit Erleada against Nubeqa. The survival benefit ultimately favored Erleada in metastatic castration-sensitive prostate cancer. Bayer disputed J&J’s analysis in a lawsuit earlier this year. Erleada first hit the scene in 2018 with an approval for non-metastatic castration-resistant prostate cancer, nabbing its next indication in metastatic castration-sensitive prostate cancer the following year. So far, the drug has treated more than 340,000 patients worldwide, J&J said.  In 2025, Erleada generated global sales of $3.57 billion, up 19.2% from 2024. The drug is one of a few that J&J is centering its ambitious oncology efforts in as it looks to become the “number 1 company in oncology by 2030,” as CEO Joaquin Duato put it on a Friday appearance on CNBC. 

Phase II ARACOG (AFT-47) head-to-head trial met its primary endpoint, with patients treated with NUBEQA® (darolutamide) showing a decline in maximally changed cognitive domain (MCCD) by 24 weeks, with a median maximal cognitive decline of -15.8% for NUBEQA versus -36.1% with enzalutamide in maximally changed cognitive domain (MCCD) at 24 weeks (p=0.009) in men with metastatic and non-metastatic castration-resistant prostate cancer (CRPC) or metastatic castration-sensitive prostate cancer (mCSPC) in a trial conducted by Alliance Foundation Trials All patients who switched treatment had been randomized to enzalutamide and later moved to NUBEQA, driven predominantly by objective or subjective cognitive decline Primary results from the Phase II ARACOG trial were presented as an oral abstract at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and highlighted in the Press Program LinkedIn Email Facebook X WHIPPANY, N.J. May 30, 2026 – Primary results from the Phase II ARACOG (AFT-47) trial, a head-to-head randomized trial conducted by Alliance Foundation Trials LLC, showed that patients treated with NUBEQA® (darolutamide; n=55) experienced significantly less decline in objective cognitive performance compared with those treated with enzalutamide (n=56). NUBEQA is indicated in the U.S. for the treatment of adult patients with metastatic castration-sensitive prostate cancer (mCSPC) both with and without docetaxel, and for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC).1 The trial met its primary endpoint, with median cognitive change from baseline to 24 weeks in maximally changed cognitive domain (MCCD) measuring -15.8% (-38.8, -2.6) for NUBEQA compared to -36.1% (-59.3, -16.7) for enzalutamide (p=0.009) in patients with advanced prostate cancer.2 Individual cognitive domain scores increased with NUBEQA, while scores remained stable or showed mild decline with enzalutamide.2 Cognitive function was measured objectively across domains including executive function, working memory, visual memory and attention. The largest percentage change between NUBEQA and enzalutamide was observed in executive function and working memory. Executive function and working memory are primarily responsible for short term memory and management of tasks in the brain, such as following conversations, remembering directions or keeping track of information. Results were presented today as an oral abstract at the American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #5005; May 30, 2026. 4:24 – 4:36 PM CDT) in Chicago. “At Bayer, we are committed to supporting people living with prostate cancer by advancing innovative treatment options,” said Dr. Frank Verholen, Global Medical & Evidence Lead for NUBEQA at Bayer. “Data have demonstrated that darolutamide does not have the same impact on the central nervous system as enzalutamide.” Secondary endpoints of ARACOG included comparison in rates of crossover, which was permitted at 12 or 24 weeks for significant pre-specified decline in cognitive testing or patient-reported outcome measures, or for central nervous system-associated adverse events, including falls.2 By 24 weeks, 32 patients in the NUBEQA arm and 33 patients in the enzalutamide arm were eligible for crossover.2 Of the 23 patients who crossed over, all had been randomized to enzalutamide and crossed over to NUBEQA, most commonly due to decline in objective (n=14) or subjective (n=11) cognitive testing.2 Patients qualified for cross-over based on worsening seen on objective or subjective cognitive tests. Longer-term follow-up of cognitive change and patient-reported outcome measure (PROM) analyses are ongoing. Prostate cancer is the leading cancer diagnosis among men in the U.S.3 Around 313,780 men are diagnosed with prostate cancer each year in the U.S.3 By 2040, prostate cancer diagnoses are projected to increase to 2.9 million worldwide.4 For men with mCSPC, just over a third (~38%) will survive five years or more after diagnosis, and most progress to castration-resistant prostate cancer (CRPC), a condition with limited long-term survival. 5,6,7 About the ARACOG trial8ARACOG (NCT04335682) is a U.S. prospective, randomized, open-label Phase II trial conducted by the Alliance for Clinical Trials in Oncology, evaluating objective and patient-reported cognitive and quality-of-life outcomes in patients with metastatic castration sensitive prostate cancer (mCSPC), metastatic castration-resistant prostate cancer (mCRPC) or non-metastatic castration-resistant prostate cancer (nmCRPC) treated with NUBEQA or enzalutamide. Patients (N=111) were enrolled and randomized 1:1 to treatment with enzalutamide or NUBEQA. CANTAB, a validated computer-based platform evaluating five cognitive domains, was performed at baseline, 12, 24 and 48 weeks. The primary endpoint was the percent change in the maximally changed cognitive domain from baseline to 24 weeks and was compared between groups with the Wilcoxon rank sum statistic. Secondary endpoints included comparison of crossover rates. A study limitation was that crossover criteria included subjective outcomes in the context of an open-label trial. CANTAB is a research tool and not used for clinical diagnosis. About NUBEQA® (darolutamide)1NUBEQA® (darolutamide) is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription. NUBEQA was developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company. NUBEQA is an androgen receptor inhibitor indicated for the treatment of adult patients with: Non-metastatic castration-resistant prostate cancer (nmCRPC) Metastatic castration-sensitive prostate cancer (mCSPC) Metastatic castration-sensitive prostate cancer (mCSPC) in combination with docetaxel IMPORTANT SAFETY INFORMATIONWarnings & PrecautionsIschemic Heart Disease – Ischemic heart disease, including fatal cases, occurred in patients receiving NUBEQA. In a pooled analysis of ARAMIS and ARANOTE, ischemic heart disease occurred in 3.4% of patients receiving NUBEQA and 2.2% receiving placebo, including Grade 3-4 events in 1.4% and 0.3%, respectively. Ischemic events led to death in 0.4% of patients receiving NUBEQA and 0.4% receiving placebo. In ARASENS, ischemic heart disease occurred in 3.2% of patients receiving NUBEQA with docetaxel and 2% receiving placebo with docetaxel, including Grade 3-4 events in 1.3% and 1.1%, respectively. Ischemic events led to death in 0.3% of patients receiving NUBEQA with docetaxel and 0% receiving placebo with docetaxel. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue NUBEQA for Grade 3-4 ischemic heart disease. Seizure – Seizure occurred in patients receiving NUBEQA. In a pooled analysis of ARAMIS and ARANOTE, Grade 1-3 seizure occurred in 0.2% of patients receiving NUBEQA. Seizure occurred from 261 to 665 days after initiation of NUBEQA. In ARASENS, seizure occurred in 0.8% of patients receiving NUBEQA with docetaxel, including two Grade 3 events. Seizure occurred from 38 to 1754 days after initiation of NUBEQA. It is unknown whether anti-epileptic medications will prevent seizures with NUBEQA. Advise patients of the risk of developing a seizure while receiving NUBEQA and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others. Consider discontinuation of NUBEQA in patients who develop a seizure during treatment. Embryo-Fetal Toxicity – The 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 In ARAMIS, 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 included urinary retention, pneumonia, and hematuria. Fatal adverse reactions occurred in 3.9% of patients receiving NUBEQA and 3.2% of patients receiving placebo. Fatal adverse reactions that occurred in ≥2 patients who received NUBEQA included death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%). The most common (>2% with a ≥2% increase compared to placebo) adverse reactions, including laboratory test abnormalities, were increased AST (23%), decreased neutrophil count (20%), fatigue (16%), increased bilirubin (16%), pain in extremity (6%), and rash (4%). Clinically relevant adverse reactions occurring in 2% or more of patients treated with NUBEQA included ischemic heart disease (4%) and heart failure (2.1%). In ARANOTE, serious adverse reactions occurred in 24% of patients receiving NUBEQA. Serious adverse reactions in ≥1% of patients who received NUBEQA included pneumonia (2%), urinary tract infection (1.8%), musculoskeletal pain (1.6%), hemorrhage (1.6%), arrhythmias (1.3%), and spinal cord compression (1.1%). Fatal adverse reactions occurred in 4.7% of patients receiving NUBEQA and those that occurred in ≥2 patients included sepsis (1.1%), craniocerebral injury (0.4%), and myocardial infarction (0.4%). The most common (≥10% with a ≥2% increase compared to placebo) adverse reaction is urinary tract infection (12%). The most common laboratory test abnormalities (≥15% with a ≥5% increase over placebo) are increased AST (32%), increased ALT (28%), increased bilirubin (17%), and decreased neutrophil count (16%). Clinically relevant adverse reactions in <10% of patients who received NUBEQA included arrhythmia (8.8%), pneumonia (3.6%), and myocardial infarction (0.7%). In ARASENS, serious adverse reactions occurred in 45% of patients receiving NUBEQA with docetaxel. Serious adverse reactions in ≥2% of patients who received NUBEQA with docetaxel included febrile neutropenia (6%), neutrophil count decreased (2.8%), musculoskeletal pain (2.6%) and pneumonia (2.6%). Fatal adverse reactions occurred in 4% of patients receiving NUBEQA with docetaxel. Fatal adverse reactions in ≥2 patients who received NUBEQA included COVID-19/COVID-19 pneumonia (0.8%), myocardial infarction (0.3%), and sudden death (0.3%). The most common (≥10% with a ≥2% increase over placebo with docetaxel) adverse reactions are constipation (23%), rash (20%), decreased appetite (19%), hemorrhage (18%), increased weight (18%), and hypertension (14%). The most common laboratory test abnormalities (≥30%) are anemia (72%), hyperglycemia (57%), decreased lymphocyte count (52%), decreased neutrophil count (49%), increased AST (40%), increased ALT (37%), and hypocalcemia (31%). Clinically relevant adverse reactions in <10% of patients who received NUBEQA with docetaxel included fractures (8%), ischemic heart disease (3.2%), seizures (0.6%), and drug-induced liver injury (0.3%). 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 BCRP transporter. Concomitant use of NUBEQA increases the AUC and Cmax 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. NUBEQA is an inhibitor of OATP1B1 and OATP1B3 transporters. Concomitant use of NUBEQA may increase the plasma concentrations of OATP1B1 or OATP1B3 substrates. Monitor patients more frequently for adverse reactions of these drugs and consider dose reduction while patients are taking NUBEQA. Review the Prescribing Information of drugs that are BCRP, OATP1B1, and OATP1B3 substrates when used concomitantly with NUBEQA. For important risk and use information about NUBEQA, please see the accompanying full Prescribing Information. Please see the full Prescribing Information. 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 includes seven 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 BayerBayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, “Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2025, the Group employed around 88,000 people and had sales of 45.6 billion euros. R&D expenses amounted to 5.8 billion euros. About Alliance Foundation Trials, LLCAlliance Foundation Trials, LLC (AFT) is a U.S.-based research organization that develops and conducts cancer clinical trials, working closely with pharmaceutical partners, research collaborators and the Alliance for Clinical Trials in Oncology member network. AFT seeks to fulfill the vision of the Alliance for Clinical Trials in Oncology to reduce the impact of cancer on people by uniting a broad community of scientists and clinicians from many disciplines, committed to discovering, validating and disseminating effective strategies for the prevention and treatment of cancer. AFT is funded wholly by private entities and does not use any public funding. To learn more about AFT, visit AllianceFoundationTrials.org. Media Contact:Polina Miklush, Tel + 862.431.8817Email: polina.miklush@bayer.com 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) [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; June 2025.2 Morgans AK, et al. Cognitive effects of darolutamide vs enzalutamide: Results of ARACOG (AFT-47), a randomized clinical trial from the Alliance for Clinical Trials in Oncology. Abstract 5005. Presented at ASCO 2026.3 National Cancer Institute. Cancer Stat Facts: Common Cancer Sites. https://seer.cancer.gov/statfacts/html/common.html. Accessed May 2026.4 James ND et al. Lancet 2024; 403: 1683–722.5 National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program. Cancer Stat Facts Prostate Cancer. Available at: https://seer.cancer.gov/statfacts/html/prost.html. Accessed May 20266 Siegel, DA et al. MMWR Morb Mortal Wkly Rep 2020; 69:1473–14807 Hahn, A et al. Am Soc Clin Oncol Educ Book. 2018; 23;38:363–3718 ClinicalTrials.gov. NCT04335682. Androgen Receptor Directed Therapy on Cognitive Function in Patients Treated With Darolutamide or Enzalutamide (ARACOG). https://clinicaltrials.gov/study/NCT04335682. Accessed April 2026. LinkedIn Email Facebook X