Second Primary Neoplasms

PALO ALTO, Calif.--(BUSINESS WIRE)--Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, presented data today from a study showing that its methylation-based Shield™ multi-cancer detection (MCD) test demonstrated high specificity and clinically meaningful sensitivity across ten tumor types,* while also providing information to guide clinical diagnostic evaluation. The study was presented at the 2025 American Association for Cancer Research (AACR) annual meeting. Results of the study served as the basis for the selection of the blood-based Shield MCD test by the National Cancer Institute (NCI) for inclusion in its upcoming Vanguard Study evaluating emerging MCD technology. "This strong data reinforces the potential of the Shield test to detect multiple cancers earlier through a simple blood draw." Data presented in the oral session titled “Evaluation of a plasma cell-free DNA methylation-based multi-cancer detection test” showed that the Shield MCD test demonstrated 98.5% specificity and 60% overall sensitivity, with 74% sensitivity across the six most aggressive cancers (defined as those with the shortest survival rates), including esophageal-gastric, hepatocellular, lung, ovarian and pancreas. The test also demonstrated 89% accuracy for primary or secondary cancer signal of origin (CSO) prediction. “There are still many types of cancer that are difficult to detect with existing technologies until the late stages. This strong data reinforces the potential of the Shield test to detect multiple cancers earlier through a simple blood draw,” said AmirAli Talasaz, Guardant Health co-founder and co-CEO. “This study was a critical step in evaluating this innovative technology as a new screening option we can bring to patients to help reduce cancer deaths.” The blinded case-control study evaluated samples from 778 individuals with either a known diagnosis of cancer or who were cancer free (by self-report). Age range of participants was 40-78 years (median age 62); 55% were female and 79% were white. Across the ten cancer types, overall sensitivity per type ranged from 96% (esophageal-gastric (stomach)) to 21% (prostate) at 98.5% specificity (Table 1). Table 1: Overall and per cancer Sensitivity and CSO Accuracy Results at 98.5% Specificity (n=403) Sensitivity, % Primary or Secondary CSO Accuracy, % Overall, 375 60% 89% Bladder, 13 62% 75% Breast, 86 45% 92% Colorectal, 41 83% 94% Esophageal-Gastric (Stomach) 25 96% 92% Hepatocellular, 16 94% 73% Lung, 57 67% 97% Ovarian, 20 70% 93% Pancreas, 59 68% 80% Prostate, 59 21% 83% “Impressively, this initial cohort analysis of the Shield MCD test met overall performance expectations, with particularly strong sensitivity in the six most aggressive cancers for which early detection is key,” said William Greenleaf, Ph.D., study co-author, consultant for Guardant Health and professor of genetics at Stanford University School of Medicine. “These results show this blood-based MCD test holds promise for detection of multiple cancer types, and thus for detection in asymptomatic adults when treatment is more effective.” The full data abstract and a list of all abstracts being presented at the meeting can be found on the AACR website. For more information on the NCI Vanguard Study, please visit the study website. About Guardant Health Guardant Health is a leading precision oncology company focused on guarding wellness and giving every person more time free from cancer. Founded in 2012, Guardant is transforming patient care and accelerating new cancer therapies by providing critical insights into what drives disease through its advanced blood and tissue tests, real-world data and AI analytics. Guardant tests help improve outcomes across all stages of care, including screening to find cancer early, monitoring for recurrence in early-stage cancer, and treatment selection for patients with advanced cancer. For more information, visit guardanthealth.com and follow the company on LinkedIn, X (Twitter) and Facebook. Forward-Looking Statements This press release contains forward-looking statements within the meaning of federal securities laws, including statements regarding the potential utilities, values, benefits and advantages of Guardant Health’s liquid biopsy tests or assays, which involve risks and uncertainties that could cause the actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are based on current expectations, forecasts and assumptions, and actual outcomes and results could differ materially from these statements due to a number of factors. These and additional risks and uncertainties that could affect Guardant Health’s financial and operating results and cause actual results to differ materially from those indicated by the forward-looking statements made in this press release include those discussed under the captions “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operation” and elsewhere in its Annual Report on Form 10-K for the year ended December 31, 2024, and in its other reports filed with or furnished to the Securities and Exchange Commission thereafter. The forward-looking statements in this press release are based on information available to Guardant Health as of the date hereof, and Guardant Health disclaims any obligation to update any forward-looking statements provided to reflect any change in its expectations or any change in events, conditions, or circumstances on which any such statement is based, except as required by law. These forward-looking statements should not be relied upon as representing Guardant Health’s views as of any date subsequent to the date of this press release. * Esophageal and Gastric cancers are combined in Table 1.

Peter Marks' departure after a decade as the director of the FDA's Center for Biologics Evaluation and Research left some worried about the future of cell and gene therapies. The sudden resignation of Peter Marks, M.D., Ph.D., from the FDA branch that regulates biological products for humans laid bare the vaccine skepticism underpinning Robert F. Kennedy Jr.’s new leadership in the federal healthcare system.“If you’re going to be a biotech company right now, don’t be a vaccine company,” Leerink Partners analyst Mani Foroohar, M.D., said in a recent interview.But there’s another field of human medicines managed under Marks’ previous leadership that could face significant disruptions—cell and gene therapies. To many in this realm of the biopharma industry, Marks’ exit means losing a seasoned regulator and key ally.Marks played a pivotal role in ushering in the modern era of cell and gene therapies. A year after he became the director of the Center for Biologics Evaluation and Research (CBER) in 2016, his department approved the very first CAR-T cell therapy, Novartis’ Kymriah, opening up a drug class that offers the hope of a potential cure for patients with once difficult-to-treat blood cancers. That same year, the FDA cleared the U.S.’ first gene therapy, Roche’s Luxturna.In a landmark approval by Marks’ CBER at the end of 2023, Vertex and CRISPR Therapeutics’ Casgevy became the first treatment based on the Nobel Prize-winning CRISPR gene-editing system.  And last year, Marks oversaw the go-ahead of Iovance Biotherapeutics’ Amtagvi, the first cell therapy for solid tumors.Amid all of these developments, Marks wasn’t just a bystander but rather an outspoken champion of novel technologies and an advocate of regulatory flexibility to accelerate approvals.“We want to lean into accelerated approval whenever we can, particularly in the rare disease space, because if you have patients in need, getting something to them a year or two sooner can make the difference,” Marks said at the 2024 DIA Global Forum.The former CBER chief also worked to streamline the interactions between the agency and developers of cell and gene therapies. He introduced INTERACT meetings, which offer sponsors of advanced biological therapies the opportunity to gain early guidance from the FDA on a product development plan. He was also instrumental in the idea of a platform designation to significantly slash development timelines and regulatory work around follow-on therapies based on reproducible technology.Marks wasn’t the first senior FDA leader to exit under the new administration. His counterpart at the Center for Drug Evaluation and Research (CDER), Patrizia Cavazzoni, M.D., had left in January. But Marks’ departure was more poignantly felt by the industry, partly because of the duration of his leadership and “how he has really changed the character of—and approach at—CBER during his tenure,” Foroohar said.While small molecule drug regulations are well established, CBER requires more regulatory handholding because of the novelty and complexity of advanced technologies, Foroohar added.As Foroohar put it, Marks “was a driver of a lot of acceleration” for the cell and gene therapy space.Now, with Marks’ departure—plus a massive workforce reduction at the FDA—that trajectory looks to be under threat. Plus, any government-related hits would serve as a double whammy for an industry that’s already undergoing a serious crisis marked by pipeline discontinuations, layoff rounds, business closures, funding challenges, commercialization struggles and a Big Pharma retreat. Interpreting the impactFollowing news of Marks’ sudden departure, investors in vaccine and cell & gene therapy biotechs hit the exit, too.On Monday, besides the widely reported selloffs at Moderna and Novavax, CRISPR Therapeutics’ stock was down 8%, while share prices for base editing specialists Beam Therapeutics and Verve Therapeutics each dropped 12%. And allogeneic cell therapy leader Allogene Therapeutics also lost about 6% in market value.After the initial shock, industry watchers were left parsing through the implications for biopharma companies. Some within the industry are openly worried about the future of cell and gene therapies, even though Marks’ high-profile resignation was focused overwhelmingly on disagreements around vaccine regulations.“We MUST get Dr. Marks reinstated within the next 30 days,” Nicole Paulk, Ph.D., CEO of gene therapy startup Siren Biotechnology, posted on X on March 29.“We MUST protect Dr. Verdun at all costs,” she continued, referring to Nicole Verdun, M.D., director of CBER’s all-important Office of Therapeutic Products (OTP), which more directly evaluates cell and gene therapies. “What we do in the next 30 days may well dictate the future of #GeneTherapy #CellTherapy #Vaccines #GeneEditing for the next 100 years. We must act NOW!”Still, given how harshly Marks criticized RFK Jr. in his resignation letter (PDF), it seems “fairly unlikely” that Marks will be reinstated, Foroohar said. Besides Paulk, many others in the biopharma industry have expressed concern at Mark’s departure. Talking about the bigger biopharma sector, trade group Biotechnology Innovation Organization CEO John Crowley said in a Saturday statement: “We are deeply concerned that the loss of experienced leadership at the FDA will erode scientific standards and broadly impact the development of new, transformative therapies to fight diseases for the American people.”Some, however, are more optimistic.Stephen Majors, VP of global communications at the Alliance for Regenerative Medicine, is hopeful that cell and gene therapies won’t land in RFK Jr.’s crosshairs. Majors pointed to positive comments in the HHS secretary’s written testimony to Sen. Tim Scott during this confirmation hearing, as well as from Trump’s White House on the establishment of the Make America Healthy Again Commission, which brought up gene therapies for sickle cell disease as a noteworthy achievement.“I’ve spoken before on the future of gene therapies and the potential for developing technologies, like CRISPR-Cas9, to one day provide treatments for rare diseases like sickle cell,” RFK Jr. said in his response to Sen. Scott. “I am so excited that sickle cell disease patients now have two potential one-time cures, one developed with the CRISPR technology.”From Wall Street’s perspective, Citi analysts in a Monday note said they do not believe that Marks’ departure “will usher in a new period of regulatory uncertainty or questionable approvals.” Still, the analysts recognized Marks’ key role in regulatory policies toward cell and gene therapies.The analysts argued that it’s natural to have leadership turnover at federal agencies in a new administration, and that the FDA knows how to uphold continuity of approval standards.Similarly, a Jefferies team led by analyst Andrew Tsai also struck a positive note in a Saturday report to clients.Pointing to Marks’ comments in his resignation letter, Tsai concluded that “we do not see increased regulatory risk for sponsors currently working with CDER/CBER on some form an expedited pathway for rare diseases.”Marks highlighted the “unwavering commitment to public health priorities” that CBER has applied to “the development of cell and gene therapies to address both hereditary and acquired rare diseases.” CBER staffers are committed to “increased communication” with product developers and have been “exploring the dramatic transformation of our regulatory approach to expedite the delivery of directly administered genome editing products,” he wrote.However, whether those efforts will continue under Marks’ replacement—or face major disruptions—remains an open question. Two potential outcomesDepending on Marks’ potential successor, Foroohar envisioned the twin possibilities of relative stability or turmoil for cell and gene therapies. Until the agency provides comments, Foroohar is not favoring any scenario because “we don’t even have tea leaves yet.” That was on Monday.Tuesday afternoon, the FDA announced the appointment of Scott Steele, Ph.D., as acting director of CBER. Steele holds a Ph.D. in molecular biology from Princeton and has been a full-time senior adviser at CBER since late 2022. And outdated resume (PDF) of Steele’s on the FDA’s website shows he received predoctoral training in genetics at the National Institutes of Health until 1998.In Foroohar’s two scenarios, promoting an internal CBER leader would be “a strong indication that the status quo, philosophically, is going to continue for cell and gene therapy.”Despite the positive sign, Steele is at least for now only filling the role on an interim basis. Even among traditional institutionalists, Marks “had a more forceful view in favor of regulatory flexibility” and “a more high-touch regulatory approach with cell and gene therapy in particular,” Foroohar said. This suggests Marks’ stance toward these novel technologies appeared to be more favorable than many of his FDA colleagues.Marks brought to light his openness—particularly toward gene therapies—in his controversial decisions on Sarepta Therapeutics’ Duchenne muscular dystrophy treatment Elevidys. The former CBER chief stepped in to overrule objections from internal FDA reviewers twice for Elevidys’ initial accelerated approval and a traditional approval last year despite the failure of a confirmatory trial.“When we are on the leading-edge of science, we’re going to make mistakes sometimes, and we may not have the rock-solid evidence always,” Marks said during the Fierce Cell & Gene virtual event last fall. “But I think our commitment is that we will do our best to weigh the benefits, risks and uncertainty and wrap that up in terms of the other available potential therapies to make the best decision we can.”Elevidys may have been an isolated event, but it’s possible at a CBER without Marks that cell and gene therapies are forced to contend with more stringent rules, William Blair analysts said in a Monday note.The other scenario in Foroohar’s modeling could be more chaotic.“If we see someone whose background is much less technical than one would expect, more of a political appointee, doesn’t have direct regulatory experience, perhaps someone who doesn’t have a lot of direct scientific drug development experience, you would start to worry that that is a case where you’re going to see a lot more destruction,” Foroohar said.In this scenario, things could go bad for cell and gene therapies in two divergent ways, he figured.A political appointee could be more skeptical of the biopharmaceutical industry as a whole, adopting a stricter approach to accelerated approvals and making clinical development more difficult and costly.Alternatively, an FDA outsider could come with much greater regulatory flexibility than even Marks, falling closer to the “right to try” camp, Foroohar explained. There were advocates for that ideology under President Trump’s first term, he noted.That approach may come as a near-term positive for the cell and gene industry. But less scientific rigor would eventually be harmful to the health of the industry, Foroohar argued.“There’s a risk that if you have a very flexible regulatory profile, you start to have products that are approved with labeled indications and datasets that don’t clearly differentiate clinical data,” Foroohar said.As a result, payers would balk at reimbursement even for approved agents, which Foroohar views would be a “more profound long-term challenge to the industry.” A greater concernAlthough a trailblazer and a visible leader, Marks is just one person. To Foroohar, a potential bigger FDA issue threatening the growth of cell and gene field is the likely loss of talented staff at CBER.“The greater concern is that you’ll see a bleeding away either from headcount reductions or from […] voluntary departures of reviewers, CMC staff, etc., the boots on the ground […] as you see people struggle with working under a leadership […] in an agency where they feel like the mission is not respected or they don’t have support from the administration.”Lola Fashoyin-Aje, M.D., an FDA veteran who was tapped in early 2024 to lead CBER’s office of clinical evaluation focused on cell and gene therapies, left the agency a few weeks ago. Before CBER, Fashoyin-Aje worked at the FDA’s Oncology Center of Excellence, where she formed and served as the program lead of Project Equity, an initiative designed to promote racial diversity in clinical trials. Her departure came shortly after the Trump administration banned diversity programs at federal agencies.“There’s going to be a lot of departures behind Peter [Marks],” former FDA commissioner Scott Gottlieb, M.D., said Monday on CNBC’s “Squawk Box.”“If you pull bricks high up off the tower, it can be very obvious, and you can draw a lot of attention and also be unlikely to implode the entire structure,” Foroohar said, drawing an analogy between the FDA staffing situation and the game Jenga. “But if you start pulling all the blocks out from the middle and the bottom, you can pretty quickly collapse the infrastructure and make it wobbly very quickly.”As to the headcount reduction, RFK Jr.’s massive layoff round targeting 3,500 FDA employees—out of 10,000 for the entire HHS—appears to have affected industry-facing staffers even though core drug reviewers have been spared.Nearly the entire FDA team involved with negotiating industry user fees has been terminated, Politico’s AgencyIQ reported Tuesday, citing several sources close to the situation. The FDA and the biopharma industry need to agree on user fee programs, including the Prescription Drug User Fee Act (PDUFA) that governs the evaluation of drugs, to ensure that the agency has enough resources to provide predictable timelines for its review process.RFK Jr. has in the past expressed skepticism toward user fee programs—which are considered a bedrock of FDA operations—out of concerns of undue industry influence.“An FDA reviewer needs the support of others,” Leerink’s Foroohar said. “There’s all kinds of other infrastructure necessary for them to allow a reviewer to do their job.”And it’s not as if CBER is overstaffed, at least according to Marks and Foroohar. The FDA’s struggle to hire and retain talent to handle the influx of complicated cell and gene therapy programs in the past few years has been no secret among industry watchers.“I suspect we’re going to need more headcount in that area very soon,” Marks said last April during an Alliance for a Stronger FDA webinar. At that time, the agency was still hiring up and evaluating the resources necessary to “really make the transformation to a very high performing organization,” he said.“Don’t be surprised if, as we move through the next year or so, we come up with some asks,” Marks said during the webinar.   A regulatory retreat?Now, instead of bulking up, the FDA is slimming down.The current headcount reduction at the FDA is reportedly targeting communications, policy and operations functions. But some FDA operations that are critical to the industry beyond specific product reviews may be dependent on those staffers. “We’re advocating for OTP to be able to continue in its work, and part of that is maintaining the ability to have these early communications with companies,” Majors at the Alliance for Regenerative Medicine said. “Those early interactions are very, very important in terms of being able to move programs along quickly.”For example, on the policy side, the FDA in May 2024 laid out a draft guidance on a new platform designation, which aims to provide an expedited pathway for the development of novel therapies that utilize the same reproducible technology, such as a gene-editing system. The platform would save the FDA a figurative “three billion visits” by drug developers every time they try to use the same technology to edit a disease gene, Marks said at the American Society of Gene and Cell Therapy meeting last year.During the Fierce Cell & Gene event last year, Marks also said that his department was re-evaluating the class-wide boxed warnings about secondary cancers that it had previously slapped on existing commercial CAR-T therapies for blood cancers. Companies are closely following the FDA’s decision on the warning as they try to develop CAR-T products for more prevalent conditions, such as autoimmune diseases, which entail entirely different benefit-risk calculations from cancers.At the Alliance for a Stronger FDA webinar last year, Marks touted the Support for clinical Trials Advancing Rare disease Therapeutics (START) pilot program. It offers constant communication and clinical development guidance for companies developing treatments for rare disease to shorten their development timeline.“If we can show even a 10% decrease in time that translates into a sufficiently large number of dollars across different rare disease programs, that one could potentially easily justify staffing up and the number of reviewers that would need to be brought on board to make this a regular procedure,” Marks said of the pilot.Whether the personnel changes would delay the formal rollout of those initiatives remains to be seen.“Every signal that we have is that they are supportive of cell and gene therapy,” Majors said of the Trump administration. “We just want to make sure that […] even if CGT was not the target, that there isn’t collateral damage based on the actions they’re taking with vaccines, specifically, and then, more broadly, with everything they’re doing in the reorganization of FDA.”

WHIPPANY, N.J.--( BUSINESS WIRE )--Bayer will present new data from its prostate cancer portfolio at the upcoming American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, taking place in San Francisco, California, from February 13-15, 2025. These presentations reinforce Bayer´s commitment to advancing treatments across different stages of prostate cancer. Data will include a subgroup analysis from the investigational Phase III ARANOTE trial, evaluating the efficacy and safety of NUBEQA ® (darolutamide) and androgen-deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) by disease volume. Subgroup analyses from the investigational Phase III ARASENS trial will be presented, including evaluating age-related efficacy and safety of NUBEQA plus ADT and docetaxel in patients with mHSPC and an analysis of concomitant granulocyte colony-stimulating factor (G-CSF) use in maintaining an efficacious dose and safe delivery of docetaxel in combination with NUBEQA in patients with mHSPC. Lead-in phase results will be presented from the investigational Phase II ARAMON trial, investigating NUBEQA monotherapy in patients with castration-sensitive prostate cancer (CSPC) after biochemical recurrence (BCR) and other data to be presented will focus on clinical use and outcomes of androgen-receptor pathway inhibitors triplet therapy for mHSPC. A trial-in-progress update will also be presented for the ongoing investigational Phase III ARASTEP trial investigating NUBEQA plus ADT in patients with high-risk BCR of prostate cancer. NUBEQA is indicated in the U.S. for the treatment of adult patients with mHSPC in combination with docetaxel and for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC). 1 In radiopharmaceuticals, investigator-initiated research will be presented on XOFIGO ® (radium-223 dichloride) without ADT in patients with BCR and positron emission tomography (PET) findings in the bones. Investigator-initiated research will be presented evaluating the safety and efficacy of retreatment of metastatic castration-resistant prostate cancer (mCRPC) patients with XOFIGO therapy in daily practice. Data from three Real World Evidence studies, reviewing data from over 30 observational studies, will be presented. XOFIGO is indicated in the U.S. for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases and no known visceral metastatic disease. 2 Details on selected abstracts from Bayer at the 2025 ASCO GU Cancers Symposium are listed below: NUBEQA (darolutamide) Darolutamide plus ADT in patients with metastatic hormone-sensitive prostate cancer (mHSPC) by disease volume: Subgroup analysis of the phase 3 ARANOTE trial Abstract: 151; February 13. 11:25 AM – 12:45 PM PST Age-related efficacy and safety of darolutamide plus androgen-deprivation therapy (ADT) and docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC): a subgroup analysis of ARASENS Abstract: 143; February 13. 11:25 AM – 12:45 PM PST Concomitant G-CSF use in maintaining an efficacious dose and safe delivery of docetaxel in combination with darolutamide in patients with metastatic hormone sensitive prostate cancer (mHSPC): ARASENS, a phase 3 study Abstract: 152; February 13. 11:25 AM – 12:45 PM PST Darolutamide monotherapy in patients with castration-sensitive prostate cancer (CSPC) after biochemical recurrence (BCR): ARAMON lead-in phase results Abstract: 150; February 13. 11:25 AM – 12:45 PM PST Clinical use and outcomes of Androgen-Receptor pAthwAy inhibitors Triplet therapy for metastatic hormone-sensitive prostate cancer (ARAAT) – Real World Evidence (RWE) Abstract: 66; February 13. 11:25 AM – 12:45 PM PST Darolutamide plus androgen-deprivation therapy (ADT) in patients with high-risk biochemical recurrence (BCR) of prostate cancer: A phase 3, randomized, double-blind, placebo-controlled study (ARASTEP) - Trial in Progress (TiP) Abstract: TPS432; February 13. 11:25 AM – 12:45 PM PST XOFIGO (radium-223 dichloride) Re-treatment of metastatic castration-resistant prostate cancer patients with radium-223 therapy in daily practice - Investigator-Initiated Research (IIR) Abstract: 183; February 13. 11:25 AM – 12:45 PM PST Radium 223 without Androgen Deprivation Therapy (ADT) in Patients (Pts) with Biochemically Recurrent Prostate Cancer (BCR) and PET Findings in the Bones - Investigator-Initiated Research (IIR) Abstract: 180; February 13. 11:25 AM -12:45 PM PST Effectiveness and safety of radium-223 in men with metastatic castration-resistant prostate cancer (mCRPC): A systematic literature review of 48 real-world studies – Real World Evidence (RWE) Abstract: 81; February 13. 11:25 AM – 12:45 PM PST Real-world treatment patterns and survival in men with metastatic castration-resistant prostate cancer (mCRPC) who previously progressed from metastatic hormone-sensitive prostate cancer (mHSPC) between 2020 to 2023 in the United States – Real World Evidence (RWE) Abstract: 99; February 13. 11:25 AM -12:45 PM PST Treatment patterns and survival in men with metastatic castration-resistant prostate cancer (mCRPC): A systematic literature review of 35 real-world observational studies – Real World Evidence (RWE) Abstract: 101; February 13. 11:25 AM -12:45 PM PST About NUBEQA ® (darolutamide) 1 NUBEQA ® (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 is 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 hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel IMPORTANT SAFETY INFORMATION Warnings & Precautions Ischemic Heart Disease – In a study of patients with nmCRPC (ARAMIS), ischemic heart disease occurred in 3.2% of patients receiving NUBEQA versus 2.5% receiving placebo, including Grade 3-4 events in 1.7% vs. 0.4%, respectively. Ischemic events led to death in 0.3% of patients receiving NUBEQA vs. 0.2% receiving placebo. In a study of patients with mHSPC (ARASENS), ischemic heart disease occurred in 3.2% of patients receiving NUBEQA with docetaxel vs. 2% receiving placebo with docetaxel, including Grade 3-4 events in 1.3% vs. 1.1%, respectively. Ischemic events led to death in 0.3% of patients receiving NUBEQA with docetaxel vs. 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 – In ARAMIS, Grade 1-2 seizure occurred in 0.2% of patients receiving NUBEQA vs. 0.2% receiving placebo. Seizure occurred 261 and 456 days after initiation of NUBEQA. In ARASENS, seizure occurred in 0.6% of patients receiving NUBEQA with docetaxel, including one Grade 3 event, vs. 0.2% receiving placebo with docetaxel. Seizure occurred 38 to 340 days after initiation of NUBEQA. It is unknown whether antiepileptic 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 – 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 vs. 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 vs. 3.2% of patients receiving placebo. Fatal adverse reactions in 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 adverse reactions (>2% with a ≥2% increase over placebo), including laboratory test abnormalities, were increased AST, decreased neutrophil count, fatigue, increased bilirubin, pain in extremity and rash. Clinically relevant adverse reactions occurring in ≥2% of patients treated with NUBEQA included ischemic heart disease and heart failure. In ARASENS, serious adverse reactions occurred in 45% of patients receiving NUBEQA with docetaxel vs. 42% of patients receiving placebo with docetaxel. Serious adverse reactions in ≥2% of patients who received NUBEQA with docetaxel included febrile neutropenia (6%), decreased neutrophil count (2.8%), musculoskeletal pain (2.6%), and pneumonia (2.6%). Fatal adverse reactions occurred in 4% of patients receiving NUBEQA with docetaxel vs. 4% of patients receiving placebo with docetaxel. Fatal adverse reactions in patients who received NUBEQA included COVID-19/COVID-19 pneumonia (0.8%), myocardial infarction (0.3%), and sudden death (0.3%). The most common adverse reactions (≥10% with a ≥2% increase over placebo with docetaxel) were constipation, rash, decreased appetite, hemorrhage, increased weight, and hypertension. The most common laboratory test abnormalities (≥30%) were anemia, hyperglycemia, decreased lymphocyte count, decreased neutrophil count, increased AST, increased ALT, and hypocalcemia. Clinically relevant adverse reactions in <10% of patients who received NUBEQA with docetaxel included fractures, ischemic heart disease, seizures, and drug-induced liver injury. Drug Interactions Effect of Other Drugs on NUBEQA – Combined P-gp and strong or moderate CYP3A4 inducers decrease NUBEQA exposure, which may decrease NUBEQA activity. Avoid concomitant use. Combined P-gp and strong CYP3A4 inhibitors increase NUBEQA exposure, which may increase the risk of NUBEQA adverse reactions. Monitor more frequently and modify NUBEQA dose as needed. Effects of NUBEQA on Other Drugs – NUBEQA inhibits breast cancer resistance protein (BCRP) transporter. Concomitant use increases exposure (AUC) and maximal concentration of BCRP substrates, which may increase the risk of BCRP substrate-related toxicities. Avoid concomitant use where possible. If used together, monitor more frequently for adverse reactions, and consider dose reduction of the BCRP substrate. NUBEQA inhibits OATP1B1 and OATP1B3 transporters. Concomitant use may increase plasma concentrations of OATP1B1 or OATP1B3 substrates. Monitor more frequently for adverse reactions and consider dose reduction of these substrates. 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 . About Metastatic Hormone-Sensitive Prostate Cancer Prostate cancer is the second most common cancer in men and the fifth most common cause of cancer death in men worldwide. 3 In 2020, an estimated 1.4 million men were diagnosed with prostate cancer, including almost 300,000 cases in the U.S., and about 375,000 died from the disease worldwide. 4,5 At the time of diagnosis, most men have localized prostate cancer, meaning their cancer is confined to the prostate gland and can be treated with curative surgery or radiotherapy. Upon relapse when the disease will metastasize or spread, androgen deprivation therapy (ADT) is the cornerstone of treatment for this hormone-sensitive disease. Approximately 10% of men will already present with mHSPC when first diagnosed. 6,7,8 Men with metastatic hormone-sensitive prostate cancer (mHSPC) will start their treatment with hormone therapy, such as ADT, androgen receptor inhibitor (ARi) plus ADT or a combination of the chemotherapy docetaxel and ADT. Despite this treatment, most men with mHSPC will eventually progress to castration-resistant prostate cancer (CRPC), a condition with limited survival. About XOFIGO (radium Ra 223 dichloride) Injection 2 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 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 includes 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. 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 2023, the Group employed around 100,000 people and had sales of 47.6 billion euros. R&D expenses before special items amounted to 5.8 billion euros. For more information, go to www.bayer.com . © 2025 Bayer BAYER, the Bayer Cross, NUBEQA and XOFIGO are registered trademarks of Bayer. Find more information at www.pharma.bayer.com Our online press service is just a click away: www.bayer.us/en/newsroom Follow us on Facebook: http://www.facebook.com/pharma.bayer Follow us on X: https://X.com/BayerUS 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 NUBEQA ® (darolutamide) [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; October 2023. XOFIGO ® (radium Ra 223 dichloride) Injection [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; October 2024. Hyuna S et al. Ca Cancer J Clin 2021 ; 71:209–249. Prostate Cancer: Statistic. Cancer.Net. https://www.cancer.net/cancer-types/prostate-cancer/statistics . September 2024. American Cancer Society. Cancer Facts & Figures 2024. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/2024-cancer-facts-figures.html . September 2024. Piombino C et al. Cancers (Basel). 2023 Oct 11;15(20):4945. Helgstrand JT et al. Cancer. 2018;124(14):2931-2938. Buzzoni C et al. Eur. Urol. 2015;68:885–890.