Janssen to Highlight Depth of Solid Tumor Portfolio at ASCO GU

RARITAN, N.J., February 3, 2020 – The Janssen Pharmaceutical Companies of Johnson & Johnson announced today multiple data presentations from a robust solid tumor portfolio that will be featured at the American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, taking place February 13-15 in San Francisco. Company-sponsored data presentations will include clinical results for ERLEADA^® (apalutamide) and niraparib in prostate cancer; and BALVERSA™ (erdafitinib) in bladder cancer.

“We are committed to improving outcomes in patients with prostate and bladder cancer where high unmet needs continue to persist despite advancements in treatment,” said Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Janssen Research & Development, LLC. “At this year’s meeting, we look forward to highlighting results from our GU portfolio and pipeline, including a new analysis of time to second progression or death after initial treatment with ERLEADA from the Phase 3 TITAN study in patients with metastatic castration-sensitive prostate cancer; and new data for BALVERSA in combination with an anti-PD-1 monoclonal antibody.”

Highlights from the Janssen oncology portfolio and pipeline will include:

New Analyses from the Phase 3 TITAN Study of ERLEADA^® in Metastatic Castration-Sensitive Prostate Cancer (mCSPC)

An oral presentation will feature a post-hoc analysis of data from the Phase 3 TITAN study on the time to second progression (PFS2) or death at any time for patients receiving hormone versus taxane therapy after initial treatment with ERLEADA^® (Abstract #82).

A poster presentation will highlight ERLEADA^® efficacy and safety results in high- versus low-risk patients with mCSPC (Abstract #87).

Niraparib Results in the Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC) and Biallelic DNA-Repair Gene Defects

A poster presentation will include an updated analysis from the Phase 2 GALAHAD study evaluating correlative measures of tumor response in patients with mCRPC and biallelic DNA-repair gene defects, including patients with BRCA1/2 gene mutations (Abstract #118).

BALVERSA^TM and Cetrelimab Combination Results in Metastatic Urothelial Carcinoma (mUC) in Patients with Genetic Alterations

A poster presentation (Abstract #511) will report results from the Phase 1b/2 NORSE study evaluating BALVERSA^TM in combination with cetrelimab, an anti-PD-1 monoclonal antibody, in patients with locally advanced or mUC with select fibroblast growth factor receptor (FGFR) genetic alterations.

Company-sponsored abstracts to be presented at the meeting include:

About ERLEADA^® (apalutamide)
ERLEADA^® is an androgen receptor (AR) inhibitor indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and for the treatment of patients with mCSPC. ERLEADA^® received U.S. Food and Drug Administration (FDA) approval for nmCRPC on February 14, 2018 and was approved for mCSPC on September 17, 2019.[1] ERLEADA^® is taken orally, once daily, with or without food.¹ The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Prostate Cancer include apalutamide (ERLEADA^®) as a treatment option for patients with non-metastatic (M0) CRPC with a Category 1 recommendation for those with a PSA doubling time ≤10 months.*^[2] The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) include apalutamide (ERLEADA^®) with androgen deprivation** as a Category 1 treatment option for patients with metastatic (M1) castration-naive prostate cancer.^†5 The American Urological Association (AUA) Guidelines for Castration-Resistant Prostate Cancer (CRPC) recommend clinicians offer apalutamide (ERLEADA^®) with continued androgen deprivation therapy (ADT) as one of the treatment options for patients with nmCRPC at high risk for developing metastatic disease. (Standard; Evidence Level Grade A)***.^[3] ERLEADA^® is being studied in five Phase 3 clinical trials.

For more information about ERLEADA^®, visit www.ERLEADA.com.

* Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Prostate Cancer V.4.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed January 2020. To view the most recent and complete version of the NCCN Guidelines^®, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use, or application, and disclaims any responsibility for their application or use in any way.

** Orchiectomy, LHRH agonist, or LHRH antagonist

^† The term “castration-naive” is used to define patients who are not on ADT at the time of progression. The NCCN Prostate Cancer Panel uses the term “castration-naive” even when patients have had neoadjuvant, concurrent, or adjuvant ADT as part of radiation therapy provided they have recovered testicular function.
***Standard: Directive statement that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be taken based on Grade A or B evidence.
***Evidence Level: A designation indicating the certainty of the results as high, moderate, or low (A, B, or C, respectively) based on AUA nomenclature and methodology.

About Niraparib
Niraparib is an orally-administered selective poly ADP ribose polymerase (PARP) inhibitor that is currently being studied by Janssen for the treatment of patients with prostate cancer. Ongoing studies include the Phase 3 MAGNITUDE study evaluating niraparib in combination with ZYTIGA^® (abiraterone acetate) and prednisone in adults with metastatic prostate cancer; and QUEST, a Phase 1b/2 study of niraparib combination therapies for the treatment of mCRPC. On October 3, 2019 niraparib received Breakthrough Therapy Designation from the U.S. FDA based on the Phase 2 GALAHAD study in patients with mCRPC.
In April 2016, Janssen entered a worldwide (except Japan) collaboration and license agreement with TESARO, Inc. (now GSK), for exclusive rights to niraparib in prostate cancer. In the U.S., niraparib is indicated for the treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy; and for the treatment of adult patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency positive status.^[4] Niraparib is currently marketed by GSK as ZEJULA^®. GSK is focused on maximizing patient survival through transformational medicines for patients living with cancer. Please refer to the full Prescribing Information available at https://www.zejula.com/prescribing-information.

About BALVERSA^TM (erdafitinib)
BALVERSA™ is a once-daily, oral FGFR kinase inhibitor indicated for the treatment of adults with locally advanced or mUC that 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.^[5]

This indication was approved by the U.S. FDA on April 12, 2019 under an accelerated approval based on tumor response rate. BALVERSA™ is the first FGFR kinase inhibitor to receive U.S. FDA approval for the treatment of mUC. Patients may be eligible for BALVERSA™ based on an FDA-approved companion diagnostic. Continued approval for this indication is contingent upon verification and description of clinical benefit in confirmatory trials.5 In 2008, Janssen entered into an exclusive worldwide license and collaboration agreement with Astex Pharmaceuticals to develop and commercialize BALVERSA™.

Ongoing studies for BALVERSA™ in patients with locally advanced or mUC whose tumors have certain FGFR alterations include the Phase 2 BLC2001 study evaluating efficacy and safety, and the Phase 3 BLC3001 study evaluating BALVERSA™ compared with vinflunine, docetaxel or pembrolizumab. The development plan for BALVERSA™ also includes a Phase 2 study (NCT04083976) in patients with advanced solid tumors and FGFR alterations.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Bladder Cancer include erdafitinib (BALVERSA™) as an alternative preferred regimen for locally advanced or metastatic disease (Stage IV) (post-platinum) for patients with susceptible FGFR3 or FGFR2 genetic alterations.*[6] The NCCN Guidelines recommend molecular/genomic testing for FGFR3 and FGFR2 genetic alterations as part of a work-up of locally advanced or metastatic urothelial carcinoma.⁶

For more information about BALVERSA™, visit www.BALVERSA.com.

*Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Bladder Cancer V.2.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed January 2020. To view the most recent and complete version of the NCCN Guidelines^®, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use, or application, and disclaims any responsibility for their application or use in any way.

ERLEADA^® IMPORTANT SAFETY INFORMATION1

WARNINGS AND PRECAUTIONS
Ischemic Cardiovascular Events — In a randomized study (SPARTAN) of patients with nmCRPC, ischemic cardiovascular events occurred in 4% of patients treated with ERLEADA^® and 3% of patients treated with placebo. In a randomized study (TITAN) in patients with mCSPC, ischemic cardiovascular events occurred in 4% of patients treated with ERLEADA^® and 2% of patients treated with placebo. Across the SPARTAN and TITAN studies, 6 patients (0.5%) treated with ERLEADA^® and 2 patients (0.2%) treated with placebo died from an ischemic cardiovascular event. Patients with current evidence of unstable angina, myocardial infarction, or congestive heart failure within 6 months of randomization were excluded from the SPARTAN and TITAN studies.

Ischemic cardiovascular events, including events leading to death, occurred in patients receiving ERLEADA^®. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Consider discontinuation of ERLEADA^® for Grade 3 and 4 events.

Fractures — In a randomized study (SPARTAN) of patients with nmCRPC, fractures occurred in 12% of patients treated with ERLEADA^® and in 7% of patients treated with placebo. In a randomized study (TITAN) of patients with mCSPC, fractures occurred in 9% of patients treated with ERLEADA^® and in 6% of patients treated with placebo. Evaluate patients for fracture risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents.

Falls — In a randomized study (SPARTAN), falls occurred in 16% of patients treated with ERLEADA^® compared with 9% of patients treated with placebo. Falls were not associated with loss of consciousness or seizure. Falls occurred in patients receiving ERLEADA^® with increased frequency in the elderly. Evaluate patients for fall risk.

Seizure — In 2 randomized studies (SPARTAN and TITAN), 5 patients (0.4%) treated with ERLEADA^® and 1 patient treated with placebo (0.1%) experienced a seizure. Permanently discontinue ERLEADA^® in patients who develop a seizure during treatment. It is unknown whether anti-epileptic medications will prevent seizures with ERLEADA^®. Advise patients of the risk of developing a seizure while receiving ERLEADA^® and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others.

Embryo-Fetal Toxicity — The safety and efficacy of ERLEADA^® have not been established in females. Based on its mechanism of action, ERLEADA^® can cause fetal harm and loss of pregnancy when administered to a pregnant female. Advise males with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of ERLEADA^® [see Use in Specific Populations (8.1, 8.3)].

ADVERSE REACTIONS
Adverse Reactions — The most common adverse reactions (≥10%) that occurred more frequently in the ERLEADA^®-treated patients (≥ 2% over placebo) from the randomized placebo-controlled clinical trials (TITAN and SPARTAN) were fatigue, arthralgia, rash, decreased appetite, fall, weight decreased, hypertension, hot flush, diarrhea and fracture.

Laboratory Abnormalities — All Grades (Grade 3-4)

• Hematology — In the TITAN study: white blood cell decreased ERLEADA^® 27% (0.4%), placebo 19% (0.6%). In the SPARTAN study: anemia ERLEADA^® 70% (0.4%), placebo 64% (0.5%); leukopenia ERLEADA^® 47% (0.3%), placebo 29% (0%); lymphopenia ERLEADA^® 41% (2%), placebo 21% (2%)
• Chemistry — In the TITAN study: hypertriglyceridemia ERLEADA^® 17% (3%), placebo 12% (2%). In the SPARTAN study: hypercholesterolemia ERLEADA^® 76% (0.1%), placebo 46% (0%); hyperglycemia ERLEADA^® 70% (2%), placebo 59% (1%); hypertriglyceridemia ERLEADA^® 67% (2%), placebo 49% (0.8%); hyperkalemia ERLEADA^® 32% (2%), placebo 22% (0.5%)

Rash — In 2 randomized studies, rash was most commonly described as macular or maculopapular. Adverse reactions of rash were 26% with ERLEADA^® vs 8% with placebo. Grade 3 rashes (defined as covering >30% body surface area [BSA]) were reported with ERLEADA^® treatment (6%) vs placebo (0.5%).

The onset of rash occurred at a median of 83 days. Rash resolved in 78% of patients within a median of 78 days from onset of rash. Rash was commonly managed with oral antihistamines, topical corticosteroids, and 19% of patients received systemic corticosteroids. Dose reduction or dose interruption occurred in 14% and 28% of patients, respectively. Of the patients who had dose interruption, 59% experienced recurrence of rash upon reintroduction of ERLEADA^®.

Hypothyroidism — In 2 randomized studies, hypothyroidism was reported for 8% of patients treated with ERLEADA^® and 2% of patients treated with placebo based on assessments of thyroid-stimulating hormone (TSH) every 4 months. Elevated TSH occurred in 25% of patients treated with ERLEADA^® and 7% of patients treated with placebo. The median onset was at the first scheduled assessment. There were no Grade 3 or 4 adverse reactions. Thyroid replacement therapy, when clinically indicated, should be initiated or dose-adjusted.

DRUG INTERACTIONS
Effect of Other Drugs on ERLEADA^® — Co-administration of a strong CYP2C8 or CYP3A4 inhibitor is predicted to increase the steady-state exposure of the active moieties. No initial dose adjustment is necessary; however, reduce the ERLEADA^® dose based on tolerability [see Dosage and Administration (2.2)].

Effect of ERLEADA^® on Other Drugs — ERLEADA^® is a strong inducer of CYP3A4 and CYP2C19, and a weak inducer of CYP2C9 in humans. Concomitant use of ERLEADA^® with medications that are primarily metabolized by CYP3A4, CYP2C19, or CYP2C9 can result in lower exposure to these medications. Substitution for these medications is recommended when possible or evaluate for loss of activity if medication is continued. Concomitant administration of ERLEADA^® with medications that are substrates of UDP-glucuronosyl transferase (UGT) can result in decreased exposure. Use caution if substrates of UGT must be co-administered with ERLEADA^® and evaluate for loss of activity.

P-gp, BCRP or OATP1B1 Substrates — Apalutamide is a weak inducer of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transporting polypeptide 1B1 (OATP1B1) clinically. Concomitant use of ERLEADA^® with medications that are substrates of P-gp, BCRP, or OATP1B1 can result in lower exposure of these medications. Use caution if substrates of P-gp, BCRP or OATP1B1 must be co-administered with ERLEADA^® and evaluate for loss of activity if medication is continued.

Please see the full Prescribing Information for ERLEADA^®.

BALVERSA^TM IMPORTANT SAFETY INFORMATION5

WARNINGS AND PRECAUTIONS
Ocular Disorders – BALVERSA^TM can cause ocular disorders, including central serous retinopathy/retinal pigment epithelial detachment (CSR/RPED) resulting in visual field defect. CSR/RPED was reported in 25% of patients treated with BALVERSA^TM, with a median time to first onset of 50 days. Grade 3 CSR/RPED, involving central field of vision, was reported in 3% of patients. CSR/RPED resolved in 13% of patients and was ongoing in 13% of patients at the study cutoff. CSR/RPED led to dose interruptions and reductions in 9% and 14% of patients, respectively, and 3% of patients discontinued BALVERSA^TM. Dry eye symptoms occurred in 28% of patients during treatment with BALVERSA^TM and were Grade 3 in 6% of 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 BALVERSA^TM when CSR occurs and permanently discontinue if it does not resolve within 4 weeks or if Grade 4 in severity. For ocular adverse reactions, follow the dose modification guidelines [see Dosage and Administration (2.3)].

Hyperphosphatemia – Increases in phosphate levels are a pharmacodynamic effect of BALVERSA^TM [see Pharmacodynamics (12.2)]. Hyperphosphatemia was reported as adverse reaction in 76% of patients treated with BALVERSA^TM. The median onset time for any grade event of hyperphosphatemia was 20 days (range: 8–116) after initiating BALVERSA^TM. Thirty-two percent of patients received phosphate binders during treatment with BALVERSA^TM. Monitor for hyperphosphatemia and follow the dose modification guidelines when required [see Dosage and Administration (2.2, 2.3)].

Embryo-fetal Toxicity – Based on the mechanism of action and findings in animal reproduction studies, BALVERSA^TM can cause fetal harm when administered to a pregnant woman. In a rat embryo-fetal toxicity study, erdafitinib was embryotoxic and teratogenic at exposures less than the human exposures at all doses studied. Advise pregnant women of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment with BALVERSA^TM 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^TM and for one month after the last dose [see Use in Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.1)].

Most common adverse reactions including laboratory abnormalities ≥20% were: Phosphate increased (76%), stomatitis (56%), fatigue (54%), creatinine increased (52%), diarrhea (47%), dry mouth (45%), onycholysis (41%), alanine aminotransferase increased (41%), alkaline phosphatase increased (41%), sodium decreased (40%), decreased appetite (38%), albumin decreased (37%), dysgeusia (37%), hemoglobin decreased (35%), dry skin (34%), aspartate aminotransferase increased (30%), magnesium decreased (30%), dry eye (28%), alopecia (26%), palmar-plantar erythrodysesthesia syndrome (26%), constipation (28%), phosphate decreased (24%), abdominal pain (23%), calcium increased (22%), nausea (21%), and musculoskeletal pain (20%). The most common Grade 3 or greater adverse reactions (>1%) were stomatitis (9%), nail dystrophy*, palmar-plantar erythrodysesthesia syndrome (6%), paronychia (3%), nail disorder*, keratitis^†, onycholysis* (10%), and hyperphosphatemia.

*Included within onycholysis. †Included within dry eye.

An adverse reaction with a fatal outcome in 1% of patients was acute myocardial infarction.

Serious adverse reactions occurred in 41% of patients, including eye disorders (10%).

Permanent discontinuation due to an adverse reaction occurred in 13% of patients. The most frequent reasons for permanent discontinuation included eye disorders (6%).

Dosage interruptions occurred in 68% of patients. The most frequent adverse reactions requiring dosage interruption included hyperphosphatemia (24%), stomatitis (17%), eye disorders (17%), and palmar-plantar erythrodysesthesia syndrome (8%).

Dose reductions occurred in 53% of patients. The most frequent adverse reactions for dose reductions included eye disorders (23%), stomatitis (15%), hyperphosphatemia (7%), palmar-plantar erythrodysesthesia syndrome (7%), paronychia (7%), and nail dystrophy (6%).

Drug Interactions· Strong CYP2C9 or CYP3A4 Inhibitors: Consider alternative agents or monitor closely for adverse reactions. (7.1)

• Strong CYP2C9 or CYP3A4 inducers: Avoid concomitant use with BALVERSA^TM. (7.1)
• Moderate CYP2C9 or CYP3A4 inducers: Increase BALVERSA^TM dose up to 9 mg. (7.1)
• Serum phosphate level-altering agents: Avoid concomitant use with agents that can alter serum phosphate levels before the initial dose modification period. (2.3, 7.1)
• CYP3A4 substrates: Avoid concomitant use with sensitive CYP3A4 substrates with narrow therapeutic indices. (7.2)
• OCT2 substrates: Consider alternative agents or consider reducing the dose of OCT2 substrates based on tolerability. (7.2)
• P-gp substrates: Separate BALVERSA^TM 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 women not to breastfeed during treatment with BALVERSA^TM and for one month following the last dose.

Please click here to see full BALVERSA^TM Prescribing Information.

About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.

Learn more at www.janssen.com. Follow us at www.twitter.com/JanssenGlobal. Janssen Research & Development, LLC and Janssen Biotech, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

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Cautions Concerning Forward-Looking Statements
This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding potential benefits and further benefits of ERLEADA^®, niraparib and BALVERSA^TM. 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, any of the other Janssen Pharmaceutical Companies 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; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; 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 December 30, 2018, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in the company’s most recently filed Quarterly Report on Form 10-Q, and the company’s subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

[1] ERLEADA^® Prescribing Information, September 17, 2019.
[2] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Prostate Cancer V.4.2019. National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Updated August 2019.
[3] American Urological Association. Castration-Resistant Prostate Cancer Guidelines. http://www.auanet.org/guidelines/castration-resistant-prostate-cancer-(2013-amended-2018). Accessed February 2020.
[4] Niraparib U.S. Prescribing Information, October 2019.
[5] BALVERSA US Prescribing Information, April 2019.
[6] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Bladder Cancer V.2.2020. National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Updated January 2020.