Johnson & Johnson Highlights Ambition to Transform the Treatment of Prostate Cancer and Bladder Cancer through Data Presentations at ASCO GU Johnson & Johnson announced today new clinical and real-world evidence data will be featured in 18 abstracts at this year's ASCO GU Symposium (San...

Clinical and real-world evidence data support treatment with ERLEADA ® (apalutamide) and niraparib plus abiraterone acetate given with prednisone in patients with prostate cancer

Additional updates will be presented on innovative targeted releasing systems TAR-200 and TAR-210 in bladder cancer

RARITAN, N.J. , Jan. 24, 2024 /PRNewswire/ -- Johnson & Johnson announced today new clinical and real-world evidence data will be featured in 18 abstracts at this year's ASCO GU Symposium ( San Francisco , January 25-27 ), highlighting the Company's commitment to transform the science of genitourinary (GU) cancers. Key presentations will include new real-world evidence data adding to the strong and differentiated clinical profile of ERLEADA ® (apalutamide) in the treatment of various stages of prostate cancer, patient-reported outcomes data from the Phase 3 MAGNITUDE study of niraparib plus abiraterone acetate given with prednisone, and updates on targeted releasing systems TAR-200 and TAR-210.

"We are applying our GU expertise to advance the science of prostate cancer and bladder cancer," said Kiran Patel , M.D., Vice President, Clinical Development, Solid Tumors, Johnson & Johnson Innovative Medicine. "A recent FDA approval of new labelling for ERLEADA reinforces the impact of this standard-of-care treatment on reducing PSA to undetectable levels when added to androgen deprivation therapy. With the addition of new analyses presented at ASCO GU, we are progressing in our ambition to address unmet patient needs through earlier treatment intervention with the goal of improving and extending patients' lives."

"Our data across six different mechanisms of action underscore the breadth and depth of J&J's GU portfolio and our commitment to redefine treatment paradigms and pioneer new therapeutic advances for people with prostate and bladder cancers," said Luca Dezzani , M.D., U.S. Vice President, Medical Affairs, Solid Tumors, Johnson & Johnson Innovative Medicine. "In addition to traditional endpoints like overall survival, we are committed to assessing patients' well-being and investing in studies and real-world analyses based on patient populations that reflect everyday clinical practice."

Delivering patient-centric innovation in prostate cancer

With a deep legacy in the treatment of prostate cancer, J&J is committed to improve outcomes in metastatic disease, while defining new standards of care for patients at all stages of disease. New data at ASCO GU build on the strong clinical profile of ERLEADA ® with real-world evidence supporting its impact on survival and PSA responses. Additional presentations highlight the company's commitment to advance equity in clinical trials.

Key presentations include:

Highlights include:

The complete list of Company-sponsored abstracts follows:

About ERLEADA ®

ERLEADA ® (apalutamide) is an androgen receptor signaling inhibitor indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC). ERLEADA ® received U.S. FDA approval for nmCRPC in February 2018, and received U.S. FDA approval for mCSPC in September 2019. To date, more than 150,000 patients worldwide have been treated with ERLEADA ® . Additional ongoing Phase 3 studies include ATLAS, evaluating ERLEADA ® for patients with localized prostate cancer with radiation therapy, and PROTEUS, evaluating ERLEADA ® for patients with localized prostate cancer treatment after radical prostatectomy.

For more information, visit www.ERLEADA.com .

AKEEGA ® is a combination, in the form of a dual-action tablet (DAT), of niraparib, a highly selective poly (ADP-ribose) polymerase (PARP) inhibitor, and abiraterone acetate, a CYP17 inhibitor. AKEEGA ® together with prednisone or prednisolone was approved in April 2023 by the European Medicines Agency, and in August 2023 by the U.S. FDA, for the treatment of patients with BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC). Additional marketing authorization applications are under review across a number of countries globally.

Additional ongoing studies include the Phase 3 AMPLITUDE study, evaluating AKEEGA ® with prednisone or prednisolone in a biomarker-selected patient population with metastatic castration-sensitive prostate cancer (mCSPC).

For more information, visit www.AKEEGA.com .

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. 1 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: http://www.fda.gov/CompanionDiagnostics .

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. 2

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 www.BALVERSA.com .

TAR-200 is an investigational targeted releasing system designed to provide controlled release of gemcitabine into the bladder, sustaining local drug exposure for weeks at a time. The safety and efficacy of TAR-200 are being evaluated in Phase 2 and Phase 3 studies in patients with muscle-invasive bladder cancer (MIBC) in SunRISe-2 and SunRISe-4 and non-muscle-invasive bladder cancer (NMIBC) in SunRISe-1 and SunRISe-3 .

TAR-210 is an investigational targeted releasing system designed to provide controlled release of erdafitinib into the bladder. The safety and efficacy of TAR-210 is being evaluated in a Phase 1 study in patients with MIBC and NMIBC ( NCT05316155 ).

About Cetrelimab

Cetrelimab is an investigational anti-programmed cell death receptor-1 (PD-1) monoclonal antibody being studied to treat bladder cancer, prostate cancer, melanoma, and multiple myeloma as part of a combination treatment. Cetrelimab is also being evaluated in multiple other combination regimens across the Johnson & Johnson portfolio.

AKEEGA ® IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS

The safety population described in the WARNINGS and PRECAUTIONS reflect exposure to AKEEGA ® in combination with prednisone in BRCA m patients in Cohort 1 (N=113) of MAGNITUDE.

Myelodysplastic Syndrome/Acute Myeloid Leukemia

AKEEGA ® may cause myelodysplastic syndrome/acute myeloid leukemia (MDS/AML).

MDS/AML, including cases with fatal outcome, has been observed in patients treated with niraparib, a component of AKEEGA ® .

All patients treated with niraparib who developed secondary MDS/cancer-therapy-related AML had received previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy.

For suspected MDS/AML or prolonged hematological toxicities, refer the patient to a hematologist for further evaluation. Discontinue AKEEGA ® if MDS/AML is confirmed.

Myelosuppression

AKEEGA ® may cause myelosuppression (anemia, thrombocytopenia, or neutropenia).

In MAGNITUDE Cohort 1, Grade 3-4 anemia, thrombocytopenia, and neutropenia were reported, respectively in 28%, 8%, and 7% of patients receiving AKEEGA ® . Overall, 27% of patients required a red blood cell transfusion, including 11% who required multiple transfusions. Discontinuation due to anemia occurred in 3% of patients.

Monitor complete blood counts weekly during the first month of AKEEGA ® treatment, every two weeks for the next two months, monthly for the remainder of the first year and then every other month, and as clinically indicated. Do not start AKEEGA ® until patients have adequately recovered from hematologic toxicity caused by previous therapy. If hematologic toxicities do not resolve within 28 days following interruption, discontinue AKEEGA ® and refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics.

Hypokalemia, Fluid Retention, and Cardiovascular Adverse Reactions

AKEEGA ® may cause hypokalemia and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition. In post-marketing experience, QT prolongation and Torsades de Pointes have been observed in patients who develop hypokalemia while taking abiraterone acetate, a component of AKEEGA ® . Hypertension and hypertensive crisis have also been reported in patients treated with niraparib, a component of AKEEGA ® .

In MAGNITUDE Cohort 1, which used prednisone 10 mg daily in combination with AKEEGA ® , Grades 3-4 hypokalemia was detected in 2.7% of patients on the AKEEGA ® arm and Grades 3-4 hypertension were observed in 14% of patients on the AKEEGA ® arm.

The safety of AKEEGA ® in patients with New York Heart Association (NYHA) Class II to IV heart failure has not been established because these patients were excluded from MAGNITUDE.

Monitor patients for hypertension, hypokalemia, and fluid retention at least weekly for the first two months, then once a month. Closely monitor patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalemia, or fluid retention, such as those with heart failure, recent myocardial infarction, cardiovascular disease, or ventricular arrhythmia. Control hypertension and correct hypokalemia before and during treatment with AKEEGA ® .

Discontinue AKEEGA ® in patients who develop hypertensive crisis or other severe cardiovascular adverse reactions.

AKEEGA ® may cause hepatotoxicity.

Hepatotoxicity in patients receiving abiraterone acetate, a component of AKEEGA ® , has been reported in clinical trials. In post-marketing experience, there have been abiraterone acetate-associated severe hepatic toxicity, including fulminant hepatitis, acute liver failure, and deaths.

In MAGNITUDE Cohort 1, Grade 3-4 ALT or AST increases (at least 5 x ULN) were reported in 1.8% of patients. The safety of AKEEGA ® in patients with moderate or severe hepatic impairment has not been established as these patients were excluded from MAGNITUDE.

Measure serum transaminases (ALT and AST) and bilirubin levels prior to starting treatment with AKEEGA ® , every two weeks for the first three months of treatment and monthly thereafter. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop. Elevations of AST, ALT, or bilirubin from the patient's baseline should prompt more frequent monitoring and may require dosage modifications.

Permanently discontinue AKEEGA ® for patients who develop a concurrent elevation of ALT greater than 3 x ULN and total bilirubin greater than 2 x ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation, or in patients who develop ALT or AST ≥20 x ULN at any time after receiving AKEEGA ® .

Adrenocortical Insufficiency

AKEEGA ® may cause adrenal insufficiency.

Adrenocortical insufficiency has been reported in clinical trials in patients receiving abiraterone acetate, a component of AKEEGA ® , in combination with prednisone, following interruption of daily steroids and/or with concurrent infection or stress. Monitor patients for symptoms and signs of adrenocortical insufficiency, particularly if patients are withdrawn from prednisone, have prednisone dose reductions, or experience unusual stress. Symptoms and signs of adrenocortical insufficiency may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with abiraterone acetate. If clinically indicated, perform appropriate tests to confirm the diagnosis of adrenocortical insufficiency. Increased doses of corticosteroids may be indicated before, during, and after stressful situations.

AKEEGA ® may cause hypoglycemia in patients being treated with other medications for diabetes.

Severe hypoglycemia has been reported when abiraterone acetate, a component of AKEEGA ® , was administered to patients receiving medications containing thiazolidinediones (including pioglitazone) or repaglinide.

Monitor blood glucose in patients with diabetes during and after discontinuation of treatment with AKEEGA ® . Assess if antidiabetic drug dosage needs to be adjusted to minimize the risk of hypoglycemia.

Increased Fractures and Mortality in Combination with Radium 223 Dichloride

AKEEGA ® with prednisone is not recommended for use in combination with Ra-223 dichloride outside of clinical trials.

The clinical efficacy and safety of concurrent initiation of abiraterone acetate plus prednisone/prednisolone and radium Ra 223 dichloride was assessed in a randomized, placebo-controlled multicenter study (ERA-223 trial) in 806 patients with asymptomatic or mildly symptomatic castration-resistant prostate cancer with bone metastases. The study was unblinded early based on an Independent Data Monitoring Committee recommendation.

At the primary analysis, increased incidences of fractures (29% vs 11%) and deaths (39% vs 36%) have been observed in patients who received abiraterone acetate plus prednisone/prednisolone in combination with radium Ra 223 dichloride compared to patients who received placebo in combination with abiraterone acetate plus prednisone.

It is recommended that subsequent treatment with Ra-223 not be initiated for at least five days after the last administration of AKEEGA ® , in combination with prednisone.

Posterior Reversible Encephalopathy Syndrome

AKEEGA ® may cause Posterior Reversible Encephalopathy Syndrome (PRES).

PRES has been observed in patients treated with niraparib as a single agent at higher than the recommended dose of niraparib included in AKEEGA ® .

Monitor all patients treated with AKEEGA ® for signs and symptoms of PRES. If PRES is suspected, promptly discontinue AKEEGA ® and administer appropriate treatment. The safety of reinitiating AKEEGA ® in patients previously experiencing PRES is not known.

Embryo-Fetal Toxicity

The safety and efficacy of AKEEGA ® have not been established in females. Based on animal reproductive studies and mechanism of action, AKEEGA ® can cause fetal harm and loss of pregnancy when administered to a pregnant female.

Niraparib has the potential to cause teratogenicity and/or embryo-fetal death since niraparib is genotoxic and targets actively dividing cells in animals and patients (e.g., bone marrow).

In animal reproduction studies, oral administration of abiraterone acetate to pregnant rats during organogenesis caused adverse developmental effects at maternal exposures approximately ≥0.03 times the human exposure (AUC) at the recommended dose.

Advise males with female partners of reproductive potential to use effective contraception during treatment and for 4 months after the last dose of AKEEGA ® . Females who are or may become pregnant should handle AKEEGA ® with protection, e.g., gloves.

Based on animal studies, AKEEGA ® may impair fertility in males of reproductive potential.

ADVERSE REACTIONS

The safety of AKEEGA ® in patients with BRCA m mCRPC was evaluated in Cohort 1 of MAGNITUDE.

The most common adverse reactions (≥10%), including laboratory abnormalities, are decreased hemoglobin, decreased lymphocytes, decreased white blood cells, musculoskeletal pain, fatigue, decreased platelets, increased alkaline phosphatase, constipation, hypertension, nausea, decreased neutrophils, increased creatinine, increased potassium, decreased potassium, increased AST, increased ALT, edema, dyspnea, decreased appetite, vomiting, dizziness, COVID-19, headache, abdominal pain, hemorrhage, urinary tract infection, cough, insomnia, increased bilirubin, weight decreased, arrhythmia, fall, and pyrexia.

Serious adverse reactions reported in >2% of patients included COVID-19 (7%), anemia (4.4%), pneumonia (3.5%), and hemorrhage (3.5%). Fatal adverse reactions occurred in 9% of patients who received AKEEGA ® , including COVID-19 (5%), cardiopulmonary arrest (1%), dyspnea (1%), pneumonia (1%), and septic shock (1%).

DRUG INTERACTIONS

Effect of Other Drugs on AKEEGA ®

Avoid coadministration with strong CYP3A4 inducers.

Abiraterone is a substrate of CYP3A4. Strong CYP3A4 inducers may decrease abiraterone concentrations, which may reduce the effectiveness of abiraterone.

Effects of AKEEGA ® on Other Drugs

Avoid coadministration unless otherwise recommended in the Prescribing Information for CYP2D6 substrates for which minimal changes in concentration may lead to serious toxicities. If alternative treatments cannot be used, consider a dose reduction of the concomitant CYP2D6 substrate drug.