Vinflunine

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced topline results from the confirmatory Phase 3 TROPiCS-04 study in locally advanced or metastatic urothelial cancer (mUC). The TROPiCS-04 study evaluated Trodelvy® (sacituzumab govitecan-hziy; SG) vs. single-agent chemotherapy (treatment of physicians’ choice, TPC) in patients with mUC who have previously received platinum-containing chemotherapy and anti-PD-(L)1 therapy. The study did not meet the primary endpoint of overall survival (OS) in the intention-to-treat (ITT) population. A numerical improvement in OS favoring Trodelvy was observed, and trends in improvement for select pre-specified subgroups and secondary endpoints of progression-free survival (PFS) and overall response rate (ORR) were also shown. The pre-specified subgroup analyses were not alpha-controlled for formal statistical testing. These data will be presented at an upcoming medical meeting. In the overall study population, there was a higher number of deaths due to adverse events with Trodelvy compared to TPC, which were primarily observed early in treatment and related to neutropenic complications, including infection. Gilead will further investigate these data, and is working to reiterate to treating physicians the importance of granulocyte-colony stimulating factor (G-CSF) use for the prevention of neutropenic complications. Trodelvy has a Boxed Warning for severe or life-threatening neutropenia; please see below for Important Safety Information. There are no changes to the known safety pro Trodelvy for the approved breast cancer indications or other investigational uses. To date, the Trodelvy safety pro generally well-tolerated and consistent with use in over 40,000 patients across Trodelvy’s approved indications and in clinical trials. Gilead is continuing to analyze the data and will discuss the results and next steps with the FDA. In the U.S., Trodelvy has an accelerated approval indication for patients with locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and anti-PD-(L)1 therapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials, including the TROPiCS-04 study. Metastatic UC is an aggressive disease which most commonly affects older patients with concurrent medical morbidities and additional changes related to the aging process. Despite recent advances, survival rates remain poor with only 8% of patients living beyond five years after diagnosis. These results may in part reflect the difficulty of treating patients with mUC who have previously received platinum-containing chemotherapy and checkpoint inhibitor therapy. There is an urgent need for new treatment options to help improve long-term outcomes. Gilead would like to thank the patients, families, investigators, and advocates who contributed to this important research. We remain committed to advancing care to address the unmet needs for the bladder cancer community. Trodelvy is the first approved Trop-2-directed antibody-drug conjugate (ADC), which has demonstrated meaningful survival advantages in two different types of metastatic breast cancers. There are more than 20 ongoing clinical trials for Trodelvy. Please see below for the approved U.S. Indication and additional Important Safety Information. About Metastatic Urothelial Cancer Bladder cancer is one of the most common cancers worldwide, with more than 1.6 million people living with the disease and urothelial cancer (UC) accounting for 90% of these cases. Metastatic bladder cancer is an aggressive disease and survival rates remain poor, with only 8% of patients living beyond five years after diagnosis. Despite recent advances, less than 20% of patients with metastatic bladder cancer go on to receive second-line therapy. There is an urgent need for new treatment options for patients with mUC who have progressed on available therapies to help improve long-term outcomes. About the TROPiCS-04 Study The TROPiCS-04 study is an open-label, global, multi-center, randomized Phase 3 study that evaluated Trodelvy vs. single-agent chemotherapy (treatment of physicians’ choice, TPC) in patients with locally advanced or mUC who received platinum-containing chemotherapy and checkpoint inhibitor therapy. The study enrolled 711 patients randomized 1:1 to receive either Trodelvy or one of three TPC chemotherapeutic standard of care (SOC) options: paclitaxel, docetaxel, or vinflunine. The primary endpoint was OS. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR) and duration of objective tumor response (DoR) as assessed by investigator per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and blinded independent central review (BICR). Further study details are available on clinicaltrials.gov (NCT04527991). About Trodelvy Trodelvy® (sacituzumab govitecan-hziy) is a first-in-class Trop-2-directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast, bladder and lung cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the tumor microenvironment through a bystander effect. Trodelvy is approved in almost 50 countries, with multiple additional regulatory reviews underway worldwide, for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. Trodelvy also has multiple global approvals for certain patients with pre-treated HR+/HER2- metastatic breast cancer, including in Australia, Brazil, Canada, the European Union, Israel, United Arab Emirates and the United States. In the U.S., Trodelvy has an accelerated approval for treatment of certain patients with second-line or later metastatic urothelial cancer; see below for full indication statements. Trodelvy is being explored for potential investigational use in other TNBC, HR+/HER2- and metastatic UC populations, as well as a range of tumor types where Trop-2 is highly expressed, including metastatic non-small cell lung cancer (NSCLC), head and neck cancer, gynecological cancer, and gastrointestinal cancers. U.S. Indications for Trodelvy In the United States, Trodelvy is indicated for the treatment of adult patients with: Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. Unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting. Locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. U.S. Important Safety Information for Trodelvy BOXED WARNING: NEUTROPENIA AND DIARRHEA Severe or life-threatening neutropenia may occur. Withhold Trodelvy for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Consider G-CSF for secondary prophylaxis. Initiate anti-infective treatment in patients with febrile neutropenia without delay. Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. At the onset of diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold Trodelvy until resolved to ≤Grade 1 and reduce subsequent doses. CONTRAINDICATIONS Severe hypersensitivity reaction to Trodelvy. WARNINGS AND PRECAUTIONS Neutropenia: Severe, life-threatening, or fatal neutropenia can occur and may require dose modification. Neutropenia occurred in 64% of patients treated with Trodelvy. Grade 3-4 neutropenia occurred in 49% of patients. Febrile neutropenia occurred in 6%. Neutropenic colitis occurred in 1.4%. Withhold Trodelvy for absolute neutrophil count below 1500/mm3 on Day 1 of any cycle or neutrophil count below 1000/mm3 on Day 8 of any cycle. Withhold Trodelvy for neutropenic fever. Administer G-CSF as clinically indicated or indicated in Table 1 of USPI. Diarrhea: Diarrhea occurred in 64% of all patients treated with Trodelvy. Grade 3-4 diarrhea occurred in 11% of patients. One patient had intestinal perforation following diarrhea. Diarrhea that led to dehydration and subsequent acute kidney injury occurred in 0.7% of all patients. Withhold Trodelvy for Grade 3-4 diarrhea and resume when resolved to ≤Grade 1. At onset, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment can receive appropriate premedication (e.g., atropine) for subsequent treatments. Hypersensitivity and Infusion-Related Reactions: Serious hypersensitivity reactions including life-threatening anaphylactic reactions have occurred with Trodelvy. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 35% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of Trodelvy was 0.2%. The incidence of anaphylactic reactions was 0.2%. Pre-infusion medication is recommended. Have medications and emergency equipment to treat such reactions available for immediate use. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Permanently discontinue Trodelvy for Grade 4 infusion-related reactions. Nausea and Vomiting: Nausea occurred in 64% of all patients treated with Trodelvy and Grade 3-4 nausea occurred in 3% of these patients. Vomiting occurred in 35% of patients and Grade 3-4 vomiting occurred in 2% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold Trodelvy doses for Grade 3 nausea or Grade 3-4 vomiting and resume with additional supportive measures when resolved to Grade ≤1. Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting. Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with Trodelvy. The incidence of Grade 3-4 neutropenia was 58% in patients homozygous for the UGT1A1*28, 49% in patients heterozygous for the UGT1A1*28 allele, and 43% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia was 21% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 9% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue Trodelvy based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function. Embryo-Fetal Toxicity: Based on its mechanism of action, Trodelvy can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. Trodelvy contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Trodelvy and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Trodelvy and for 3 months after the last dose. ADVERSE REACTIONS In the pooled safety population, the most common (≥ 25%) adverse reactions including laboratory abnormalities were decreased leukocyte count (84%), decreased neutrophil count (75%), decreased hemoglobin (69%), diarrhea (64%), nausea (64%), decreased lymphocyte count (63%), fatigue (51%), alopecia (45%), constipation (37%), increased glucose (37%), decreased albumin (35%), vomiting (35%), decreased appetite (30%), decreased creatinine clearance (28%), increased alkaline phosphatase (28%), decreased magnesium (27%), decreased potassium (26%), and decreased sodium (26%). In the ASCENT study (locally advanced or metastatic triple-negative breast cancer), the most common adverse reactions (incidence ≥25%) were fatigue, diarrhea, nausea, alopecia, constipation, vomiting, abdominal pain, and decreased appetite. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced neutrophils, leukocytes, and lymphocytes. In the TROPiCS-02 study (locally advanced or metastatic HR-positive, HER2-negative breast cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, alopecia, and constipation. The most frequent serious adverse reactions (SAR) (>1%) were diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), abdominal pain, colitis, neutropenic colitis, pneumonia, and vomiting (each 2%). SAR were reported in 28% of patients, and 6% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPiCS-02 study were reduced neutrophils and leukocytes. In the TROPHY study (locally advanced or metastatic urothelial cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, any infection, alopecia, decreased appetite, constipation, vomiting, rash, and abdominal pain. The most frequent serious adverse reactions (SAR) (≥5%) were infection (18%), neutropenia (12%, including febrile neutropenia in 10%), acute kidney injury (6%), urinary tract infection (6%), and sepsis or bacteremia (5%). SAR were reported in 44% of patients, and 10% discontinued due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPHY study were reduced neutrophils, leukocytes, and lymphocytes. DRUG INTERACTIONS UGT1A1 Inhibitors: Concomitant administration of Trodelvy with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with Trodelvy. UGT1A1 Inducers: Exposure to SN-38 may be reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with Trodelvy. Please see full Prescribing Information, including BOXED WARNING. About Gilead Sciences Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. Forward-Looking Statements This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including Gilead’s ability to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical trials, including those involving Trodelvy; uncertainties relating to regulatory applications and related filing and approval timelines, including pending or potential applications for Trodelvy for the treatment of metastatic and other TNBC, HR+/HER2- metastatic breast cancer, mUC, metastatic NSCLC, head and neck cancer, gynecological cancer and gastrointestinal cancer; Gilead’s ability to receive regulatory approvals for programs and/or indications that are currently under evaluation in a timely manner or at all, including the risk that the FDA may not grant full approval or may withdraw its accelerated approval for Trodelvy for the treatment of locally advanced or metastatic urothelial cancer (mUC), and the risk that any such approvals may be subject to significant limitations on use and is subject to, withdrawal or other adverse actions by the applicable regulatory authority; the possibility that Gilead may make a strategic decision to discontinue development of programs for indications that are currently under evaluation, including Trodelvy for treatment of mUC, and as a result, these programs may never be or cease to be commercialized for such indications; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and other factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation and disclaims any intent to update any such forward-looking statements. U.S. Prescribing Information for Trodelvy including BOXED WARNING, is available at . Trodelvy, Gilead and the Gilead logo are trademarks of Gilead Sciences, Inc., or its related companies. For more information about Gilead, please visit the company’s website at or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

BALVERSA® is the First and Only Targeted Therapy for Patients with Locally Advanced or Metastatic Urothelial Carcinoma and Susceptible Fibroblast Growth Factor Receptor Alterations Phase 3 THOR Study Showed a 36 Percent Reduction in the Risk of Death with BALVERSA® Versus Chemotherapy in Patients Data were featured at the European Society for Medical Oncology (ESMO) 2023 Congress and in The New England Journal of Medicine RARITAN, N.J., Jan. 19, 2024 /PRNewswire/ -- Johnson & Johnson announced today that the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) for BALVERSA® (erdafitinib) for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC) with susceptible fibroblast growth factor receptor 3 (FGFR3) genetic alterations whose disease has progressed on or after at least one line of prior systemic therapy. BALVERSA® is not recommended for the treatment of patients who are eligible for and have not received prior PD-1 or PD-L1 inhibitor therapy. This FDA action converts the April 2019 accelerated approval of BALVERSA® to a full approval based on the clinical and overall survival benefit observed in the Phase 3 THOR study. BALVERSA® is the first oral FGFR kinase inhibitor to be approved, and the first and only targeted treatment for patients with mUC and FGFR alterations. Approximately 20 percent of patients with mUC have FGFR3 genetic alterations. After one or more lines of systemic therapy, including a checkpoint inhibitor, these patients generally have a poor prognosis with few available treatment options. This approval is based on results from Cohort 1 of the randomized, controlled, open-label, multicenter Phase 3 THOR study (NCT03390504) confirming the clinical benefit of BALVERSA® in extending overall survival (OS) compared to chemotherapy in the second-line setting. Results from the study showed a 36 percent reduction in the risk of death with BALVERSA® versus chemotherapy in patients previously treated with a PD-1 or PD-(L)1 inhibitor, with those in the BALVERSA® arm living a median of over four months longer (Hazard Ratio (HR) 0.64; [95 percent Confidence Interval (CI), 0.47-0.88]; p=0.0050).1 "Based on results from randomized Phase 3 data, BALVERSA continues to demonstrate the promise of targeted therapy in the treatment of patients with advanced bladder cancer," said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Johnson & Johnson Innovative Medicine. "This important milestone reinforces our commitment to advance innovative, precision therapies in oncology and confirm the role of targeted therapy in the treatment of bladder cancer." Warnings and Precautions in the U.S. Prescribing Information include ocular disorders, hyperphosphatemia and embryo-fetal toxicity. The most common (>20%) adverse reactions, including laboratory abnormalities, were increased phosphate, nail disorders, stomatitis, diarrhea, increased creatinine, increased alkaline phosphate, increased alanine aminotransferase, decreased hemoglobin, decreased sodium, increased aspartate aminotransferase, fatigue, dry mouth, dry skin, decreased phosphate, decreased appetite, dysgeusia, constipation, increased calcium, dry eye, palmar-plantar erythrodysesthesia syndrome, increased potassium, alopecia, and central serous retinopathy. 2 Johnson & Johnson is offering BALVERSA® and associated patient services through a single-source specialty pharmacy provider, US Bioservices. This model is part of the Company's ongoing commitment to provide high-quality products, services, access, and support to healthcare professionals and patients. The current full Prescribing Information is available at . About THOR THOR (NCT03390504) is a Phase 3 randomized, open-label, multicenter study evaluating the efficacy and safety of BALVERSA®. All patients included in the study had metastatic or unresectable UC, with selected FGFR genetic alterations, and showed disease progression during or after one or two prior lines of treatment. The study compared BALVERSA® in two cohorts; BALVERSA® versus standard of care chemotherapy (investigator's choice of docetaxel or vinflunine) after at least one line of treatment including an anti-programmed death (ligand) 1 (PD-[L]1) agent (Cohort 1); and BALVERSA® compared to pembrolizumab after one prior treatment not containing an anti-PD-(L)1 agent (Cohort 2). The trial consists of screening, a treatment phase (from randomization until disease progression, intolerable toxicity, withdrawal of consent or decision by investigator to discontinue treatment) and a post-treatment follow-up (from end-of-treatment to participant's death, withdraws consent, or lost to follow-up study completion for the respective cohort, whichever comes first). A long-term extension period is planned for after the clinical cutoff date is achieved for the final analysis of each cohort for patients who continue to benefit from the study intervention. The primary endpoint of the study is OS; progression free survival (PFS), objective response rate (ORR), duration of response (DOR), patient-reported outcomes, safety, and pharmacokinetics (PK) are secondary endpoints. Results from Cohort 1 were presented in a Late-Breaking Presentation Session (Abstract #LBA4619) at the 2023 American Society of Clinical Oncology Annual Meeting.1 In June 2023, based on the recommendation of the independent data safety monitoring committee, the THOR study was stopped at the interim analysis for efficacy and all patients randomized to chemotherapy were offered the opportunity to cross over to BALVERSA®. Results from Cohort 1 and Cohort 2 of the confirmatory, Phase 3, randomized study were presented at ESMO 2023 (Abstract #2359O), and results of Cohort 1 were published in the New England Journal of Medicine in November 2023. About BALVERSA® BALVERSA® (erdafitinib) is a once-daily, oral FGFR kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC) with susceptible fibroblast growth factor receptor 3 (FGFR3) genetic alterations whose disease progressed on or after at least one line of prior systemic therapy. BALVERSA ® is not recommended for the treatment of patients who are eligible for and have not received prior PD-1 or PD-(L)1 inhibitor therapy.2 Patients are selected for therapy based on an FDA-approved companion diagnostic for BALVERSA®. Information on FDA-approved tests for the detection of FGFR genetic alterations in urothelial cancer is available at: . BALVERSA® received Breakthrough Therapy Designation from the U.S. FDA in 2018 and received accelerated approval in 2019 for the treatment of adults with locally advanced or mUC which has susceptible FGFR3 or FGFR2 genetic alterations and who have progressed during or following at least one line of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.3 The Company submitted a marketing authorization application to the European Medicines Agency in September 2023 for BALVERSA ® as a treatment for adult patients with FGFR3-altered, locally advanced unresectable or metastatic urothelial carcinoma that has progressed following therapy with a PD-(L)1 inhibitor. In 2008, Janssen Pharmaceuticals entered into an exclusive worldwide license and collaboration agreement with Astex Pharmaceuticals to develop and commercialize BALVERSA®. For more information, visit . About Urothelial Carcinoma Urothelial carcinoma, also known as transitional cell carcinoma, starts in the innermost lining of the bladder.4 It is the most common form of bladder cancer, representing more than 90 percent of all bladder cancers.5 Metastatic or unresectable disease is identified in approximately 20 percent of patients presenting with urothelial cancer, and an estimated five to eight percent of all bladder cancers. Approximately one in five patients (20 percent) diagnosed with mUC have an FGFR genetic alteration.6,7 Fibroblast growth factor receptors are a family of receptor tyrosine kinases that can be activated by genetic alterations in a variety of tumor types, and these alterations may lead to increased tumor cell growth and survival. 6,8,9,10,11 Select FGFR genetic alterations can be detected through an FDA-approved companion diagnostic. The five-year survival rate for patients with Stage IV metastatic bladder cancer that has spread to distant parts of the body is currently eight percent.12 BALVERSA® IMPORTANT SAFETY INFORMATION WARNING AND PRECAUTIONS Ocular Disorders – BALVERSA® can cause ocular disorders, including central serous retinopathy/retinal pigment epithelial detachment (CSR/RPED) resulting in visual field defect. CSR/RPED occurred in 22% of patients treated with BALVERSA, with a median time to first onset of 46 days. In 104 patients with CSR, 40% required dose interruptions and 56% required dose reductions; 2.9% of BALVERSA-treated patients required permanent discontinuation for CSR. Of the 24 patients who restarted BALVERSA after dose interruption with or without dose reduction, 67% had recurrence and/or worsening of CSR after restarting. CSR was ongoing in 41% of the 104 patients at the time of last evaluation. Dry eye symptoms occurred in 26% of BALVERSA®-treated patients. All patients should receive dry eye prophylaxis with ocular demulcents as needed. Perform monthly ophthalmological examinations during the first 4 months of treatment and every 3 months afterwards, and urgently at any time for visual symptoms. Ophthalmological examination should include assessment of visual acuity, slit lamp examination, fundoscopy, and optical coherence tomography. Withhold or permanently discontinue BALVERSA® based on severity and/or ophthalmology exam findings [see Dosage and Administration (2.3)]. Hyperphosphatemia and Soft Tissue Mineralization – BALVERSA® can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcinosis, non-uremic calciphylaxis and vascular calcification. Increases in phosphate levels are a pharmacodynamic effect of BALVERSA® [see Pharmacodynamics (12.2)]. Increased phosphate occurred in 73% of BALVERSA®-treated patients. The median onset time of increased phosphate was 16 days (range: 8–421) after initiating BALVERSA®. Twenty-four percent of patients received phosphate binders during treatment with BALVERSA®. Vascular calcification was observed in 0.2% of patients treated with BALVERSA®. Monitor for hyperphosphatemia throughout treatment. In all patients, restrict phosphate intake to 600‑800 mg daily and avoid concomitant use of agents that may increase serum phosphate levels. If serum phosphate is above 7.0 mg/dL, consider adding an oral phosphate binder until serum phosphate level returns to <7.0 mg/dL. Withhold, dose reduce, or permanently discontinue BALVERSA® based on duration and severity of hyperphosphatemia [see Dosage and Administration (2.3), Table 2: Dose Modifications for Adverse Reactions]. Embryo-Fetal Toxicity – Based on the mechanism of action and findings in animal reproduction studies, BALVERSA® can cause fetal harm when administered to a pregnant female. In a rat embryo-fetal toxicity study, erdafitinib caused malformations and embryo-fetal death at maternal exposures that were less than the human exposures at the maximum human recommended dose. Advise pregnant patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment with BALVERSA® and for one month after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with BALVERSA® and for one month after the last dose [see Use in Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.1)]. Adverse Reactions In this pooled safety population of 479 patients who received BALVERSA®, the median duration of treatment was 4.8 months (range: 0.1 to 43 months). The most common (>20%) adverse reactions were: increased phosphate, nail disorders, stomatitis, diarrhea, increased creatinine, increased alkaline phosphatase, increased alanine aminotransferase, decreased hemoglobin, decreased sodium, increased aspartate aminotransferase, fatigue, dry mouth, dry skin, decreased phosphate, decreased appetite, dysgeusia, constipation, increased calcium, dry eye, palmar-plantar erythrodysesthesia syndrome, increased potassium, alopecia, and central serous retinopathy. In Cohort 1 of the BLC3001 study: Serious adverse reactions occurred in 41% of patients who received BALVERSA®. Serious reactions in >2% of patients included urinary tract infection (4.4%), hematuria (3.7%), hyponatremia (2.2%), and acute kidney injury (2.2%). Fatal adverse reactions occurred in 4.4% of patients who received BALVERSA®, including sudden death (1.5%), pneumonia (1.5%), renal failure (0.7%), and cardiorespiratory arrest (0.7%). Permanent discontinuation of BALVERSA® due to an adverse reaction occurred in 14% of patients. Adverse reactions which resulted in permanent discontinuation of BALVERSA® in >2% of patients included nail disorders (3%) and eye disorders (2.2%). Dosage interruptions of BALVERSA® due to an adverse reaction occurred in 72% of patients. Adverse reactions which required dosage interruption in >4% of patients included nail disorders (22%), stomatitis (19%), eye disorders (16%), palmar-plantar erythrodysesthesia syndrome (15%), diarrhea (10%), hyperphosphatemia (7%), increased aspartate aminotransferase (6%), and increased alanine aminotransferase (5%). Dose reductions of BALVERSA® due to an adverse reaction occurred in 69% of patients. Adverse reactions which required dose reductions in >4% of patients included nail disorders (27%), stomatitis (19%), eye disorders (17%), palmar-plantar erythrodysesthesia syndrome (12%), diarrhea (7%), dry mouth (4.4%), and hyperphosphatemia (4.4%). Clinically relevant adverse reactions in <15% of patients who received BALVERSA® included nausea (15%), pyrexia (15%), epistaxis (13%), vomiting (10%), and arthralgia (10%). Drug Interactions Moderate CYP2C9 or Strong CYP3A4 Inhibitors: Consider alternative agents; however, if co-administration is unavoidable monitor closely for adverse reactions. (7.1) Strong CYP3A4 inducers: Avoid co-administration use with BALVERSA®. (7.1) Moderate CYP3A4 inducers: If co-administration is required at the start of BALVERSA® treatment, administer BALVERSA® at a dose of 9 mg daily. (7.1) Serum phosphate level-altering agents: Avoid co-administration use with agents that can alter serum phosphate levels before the initial dose modification period based on serum phosphate levels. (2.3, 7.1) P-gp substrates: If co-administration is unavoidable separate BALVERSA® administration by at least 6 hours before or after administration of P-gp substrates with narrow therapeutic indices. (7.2) Use in Specific Populations Lactation – Because of the potential for serious adverse reactions from erdafitinib in a breastfed child, advise lactating patients not to breastfeed during treatment with BALVERSA® and for one month following the last dose. Please click here to see full BALVERSA® Prescribing Information. About Johnson & Johnson At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at or at . Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc. are both Johnson & Johnson companies. Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of BALVERSA®. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC; Janssen Biotech, Inc., and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 1, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at , or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Biotech, Inc., nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. 1 ASCO Publications. Phase 3 THOR study: Results of erdafitinib (erda) versus chemotherapy (chemo) in patients (pts) with advanced or metastatic urothelial cancer (mUC) with select fibroblast growth factor receptor alterations (FGFRalt). Available at: 2 BALVERSA® Prescribing Information. 3 Clinicaltrials.gov. A Study of Erdafitinib in Participants With Advanced Solid Tumors and Fibroblast Growth Factor Receptor (FGFR) Gene Alterations. . Accessed May 2023. 4 American Cancer Society. "What is Bladder Cancer." Available at . Accessed May 2023. 5 National Cancer Institute. "Bladder Cancer Treatment (PDQ®)–Health Professional Version". Available at . Accessed May 2023. 6 Tomlinson DC et al. FGFR3 protein expression and its relationship to mutation status and prognostic variables in bladder cancer. J Pathol. 2007;213(1):91-98. 7 De Santis M et al. Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol. 2011;30:191-199. 8 Helsten T et al. The FGFR landscape in cancer: analysis of 4,853 tumors by next-generation sequencing. Clin Cancer Res. 2015;22(1):259-267. 9 Eisenhauer EA et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009. 45: 228-247. 10 Janssen Pharmaceuticals, Inc. Data on file. 11 U.S. and World Population Clock. Available at . Accessed May 2023. 12 Bladder Cancer: Statistics. Available at . Accessed May 2023. SOURCE Johnson & Johnson