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Modra Pharmaceuticals (“Modra”) today announced positive data from its Phase IIb trial evaluating its boosted oral taxane therapeutic, ModraDoc006/r, in patients with metastatic Castration-Resistant Prostate Cancer (mCRPC) compared to the standard-of-care, the IV chemotherapy docetaxel. ModraDoc006/r is an oral tablet formulation of docetaxel co-administered with ritonavir, a boosting agent which enhances bioavailability. In a total of 101 patients enrolled, ModraDoc006/r demonstrated a similar efficacy and an improved tolerability pro to IV docetaxel, with reduced neutropenia, neuropathy and alopecia. The trial data will be presented at the 2022 Annual American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) held from February 17-19, 2022, one year after Modra shared its initial study data at the same conference. “Completing this study is an exciting step for Modra, as we continue to demonstrate the potential of ModraDoc006/r to be a valuable alternative to IV chemotherapeutics for mCRPC,” said Colin Freund, CEO of Modra Pharmaceuticals. “Our goal with ModraDoc006/r is to offer a better tolerated, effective and more convenient oral taxane therapeutic to patients with prostate cancer, including those who cannot tolerate or otherwise access IV therapy. Based on the currently reported compelling data, we are planning out the next development steps for ModraDoc006/r, including a pivotal study. We would like to extend our sincere thanks to the patients and clinicians who participated in this study.” Out of the total study population, 49 patients received IV docetaxel and 52 ModraDoc006/r (21 on 30-20/200-100 mg (“30-20”) and 31 on 20-20/200-100 mg (“20-20”) bi-daily weekly dosing (BIDW) doses). ModraDoc006/r vs IV docetaxel demonstrated an overall response rate (ORR) of 44% vs. 39%, respectively. Prostate-Specific Antigen (PSA) responses were comparable at 50% vs. 57%, respectively. Neutropenia (low levels of neutrophils, a type of white blood cell) was eliminated with ModraDoc006/r at the 20-20 mg dose, reduced to 14% at the 30-20 mg dose vs 25% on IV docetaxel. Neuropathy (nerve damage or dysfunction) and alopecia were also reduced with ModraDoc006/r at the 20-20 mg dose compared to the 30-20 mg dose and IV docetaxel. Gastrointestinal toxicities were slightly more frequent, but still predominantly mild, in the ModraDoc006/r arm at both dose levels. “ModraDoc006/r has shown a favorable toxicity pro comparable efficacy to IV docetaxel in metastatic CRPC. Advanced prostate cancer patients frequently do not receive the benefits of IV docetaxel chemotherapy due to advanced age, comorbidities and, during the pandemic, fear of exposure to Covid-19 at infusion centers. An oral chemo that is easier to tolerate - with less risk of cytopenias, hair loss and neuropathy - would make the benefits of chemo accessible to the majority of patients with metastatic prostate cancer. Thus, there is a compelling rationale to evaluate ModraDoc006/r further,” said Ulka Vaishampayan, MD, Principal Investigator of the study and Professor of Internal Medicine, Division of Hematology/Oncology at the University of Michigan. The open label 1:1 randomized study evaluated a ModraDoc006/r BIDW regimen versus IV docetaxel 75 mg/m2 in 21-day cycles. Initially a BIDW 30-20/200-100 mg dose (representing 30 mg ModraDoc006 and 200 mg ritonavir in the morning, 20 mg ModraDoc006 and 100 mg ritonavir in the evening) was administered on days 1, 8 and 15 of a 21-day cycle. After 21 patients, the morning dose of ModraDoc006 was reduced to 20 mg to improve tolerability. All patients received 5 mg oral prednisone twice daily. The primary endpoint of the study was radiographic progression free survival (rPFS) per PCWG-3 criteria. Secondary objectives were ORR, PSA-PFS, time to skeletal related events, disease control rate, duration of response, and safety assessments. Patient reported outcomes and health-related Quality of Life (QoL) was assessed with treatment satisfaction and Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaires at baseline and after cycles 3, 6 and 10. About metastatic Castration-Resistant Prostate Cancer (mCRPC) mCRPC is an advanced form of prostate cancer and the fourth most common cause of cancer death overall. mCRPC is not amenable to surgical treatment and resistant to androgen deprivation therapy, a hormone therapy used as initial disease management to reduce growth of prostate cancer cells. About ModraDoc006/r ModraDoc006/r is a proprietary boosted taxane therapy based on docetaxel, an intravenously administered therapy, that is very broadly used in a variety of tumor types. ModraDoc006 – an oral docetaxel tablet - is given in combination with ritonavir (r), which acts as a booster to increase the systemic bioavailability of ModraDoc006. ModraDoc006/r is designed to combine the convenience and practicality of taking chemotherapy treatment at home with the potential for an improved safety profile, as compared to standard IV docetaxel. About Modra Pharmaceuticals Modra Pharmaceuticals aims to transform taxane therapy by developing therapies that are less toxic, more effective and can be taken at home in tablet form. The Company’s goal is to dramatically improve the therapeutic outcomes and everyday lives of the hundreds of thousands of cancer patients undergoing taxane therapy worldwide. Modra’s lead program completed a Phase 2b clinical study in prostate cancer, resulting in positive date further supporting the delivery, bioavailability and tolerability of its novel approach.

Blue Earth Diagnostics a Bracco company and recognized leader in the development and commercialization of innovative PET radiopharmaceuticals, today announced publication of key results from its Phase 3 SPOTLIGHT trial of 18F-rhPSMA-7.3 in recurrent prostate cancer in an abstract being presented at the ASCO 2022 Genitourinary Cancers Symposium (ASCO GU). 18F-rhPSMA-7.3 is an investigational Prostate-Specific Membrane Antigen-targeted radiohybrid (rh) PET imaging agent. The SPOTLIGHT study (NCT04186845) is a Phase 3, multi-center, single-arm imaging study, conducted in the United States and Europe to evaluate the safety and diagnostic performance of 18F-rhPSMA-7.3 PET imaging in men with suspected prostate cancer recurrence based on elevated PSA following prior therapy. This press release features multimedia. View the full release here: 18F-rhPSMA-7.3 PET Photo courtesy of Blue Earth Diagnostics. General use: This 18F-rhPSMA-7.3 PET image shows prostate cancer spread beyond the prostate region. Technical use: This 18F-rhPSMA-7.3 PET image shows detection of recurrent prostate cancer in several retroperitoneal lymph nodes, as indicated by the green arrows. Based on the majority read results from the three blinded, independent PET readers, the overall detection rate (DR) of 18F-rhPSMA-7.3 PET in the SPOTLIGHT study was 83% (322/389). When stratified by PSA level, the DRs in the 305 patients with prior prostatectomy were: PSA <0.5 ng/mL: 64% (77/120); PSA ≥0.5 and <1 ng/mL: 76% (51/67); PSA ≥1 and <2 ng/mL: 93% (41/44); PSA ≥ 2 and <5 ng/mL: 96% (43/45); PSA ≥ 5 and <10 ng/mL: 88% (14/16); and PSA ≥10 ng/mL: 100% (13/13). The study was designed to confirm positive 18F-rhPSMA-7.3 PET imaging findings using a composite Standard of Truth (SoT) consisting of either: histopathology (considered the gold standard); or conventional imaging (primarily with CT, bone scan or MRI, with fewer procedures using 18F-fluciclovine PET). In 366 men with a composite SoT (histopathology and/or conventional imaging), the patient-level Correct Detection Rate (CDR) was 57% (95% CI, 52-62). The region-level Positive Predictive Value (PPV) was 60% (55-65). However, in the subset of patients using the preferred gold standard of histopathology as the SoT (n=69), the patient-level CDR and region-level PPVs were much higher, at 81% (70-90) and 72% (63-81), respectively, providing important evidence regarding 18F-rhPSMA-7.3’s performance. Additional endpoints, including patient-level PPV and the percentage of patients upstaged by 18F-rhPSMA-7.3 PET, will be reported at future scientific meetings. No serious adverse reactions were attributed to 18F-rhPSMA-7.3 PET in the SPOTLIGHT study. Overall, 16 (4.1%) patients had at least one treatment-emergent adverse event that was considered possibly related/related to 18F-rhPSMA-7.3. The most frequently reported events were: hypertension: 1.8% (n=7); diarrhea: 1.0% (n=4); injection site reaction: 0.5% (n=2), and headache: 0.5% (n=2). The study will be discussed in an oral presentation at ASCO GU, “Detection rate of 18F-rhPSMA-7.3 PET in patients with suspected prostate cancer recurrence: Results from a phase 3, prospective, multicenter study (SPOTLIGHT)”, by Dr. David M. Schuster, MD, FACR, Winship Cancer Institute of Emory University, in person and online at the conference on Thursday, February 17, 2022, at 7:00 PM ET. The ASCO GU program guide is available here. “Up to 40% of patients who undergo radical prostatectomy, and up to 50% of patients who undergo radiation therapy will develop local or distant recurrences within 10 years, and the ability to determine the extent and location of recurrent prostate cancer to inform appropriate clinical management for these men is key for physicians and their patients,” said David M. Schuster, MD, FACR, Emory University School of Medicine, and Coordinating Investigator for the SPOTLIGHT study. “Conventional imaging techniques have many limitations in prostate cancer identification and localization, and greater imaging accuracy is needed throughout the care continuum, to optimize therapeutic decision-making. The Phase 3 SPOTLIGHT study investigated the diagnostic performance of 18F-rhPSMA-7.3 PET imaging as a potential decision-making aid in assessing suspected biochemical recurrence of the disease. Taken together, we believe these strong results support the clinical utility of 18F-rhPSMA-7.3 PET in men with recurrent prostate cancer across a wide PSA range.” “We are pleased to share these key Phase 3 SPOTLIGHT study results with the clinical community at the prestigious ASCO GU 2022 conference,” said David Gauden, D.Phil., President R&D and Chief Scientific Officer of Blue Earth Diagnostics. “SPOTLIGHT is the first of Blue Earth’s diagnostic imaging rhPSMA trials to report results, based on novel radiohybrid PSMA technology which offers potential theranostic utility in both diagnostic PET imaging and therapy. We look forward to sharing these convincing results with the U.S. Food and Drug Administration (FDA) as part of a New Drug Application for 18F-rhPSMA-7.3 PET imaging.” Dr. Gauden continued, “Blue Earth is committed to helping men with prostate cancer across the care continuum, and we particularly wish to thank the patients and clinical teams who participated in the SPOTLIGHT study, despite the many challenges COVID-19 presented. In working to fulfill our commitment to patients, we are working on a uniquely comprehensive prostate cancer portfolio, which includes 18F-fluciclovine as well as investigational rhPSMA compounds for potential use in diagnostic PET imaging and targeted radiopharmaceutical therapy. Early studies of 18F-rhPSMA-7.3 demonstrated high binding affinity for PSMA, together with biodistribution data suggesting the potential for low bladder activity. Our focus on 18F as the isotope of choice for PET imaging with rhPSMA was made in consideration of its spatial resolution and resulting high quality of PET images, and its physical half-life which greatly facilitates ease of large-scale manufacturing and distribution for broad-based patient access.” About Radiohybrid Prostate-Specific Membrane Antigen (rhPSMA) rhPSMA compounds consist of a radiohybrid (“rh”) Prostate-Specific Membrane Antigen-targeted receptor ligand which attaches to and is internalized by prostate cancer cells and they may be radiolabeled with 18F for PET imaging, or with isotopes such as 177Lu or 225Ac for therapeutic use – creating a true theranostic technology. The radiohybrid technology and rhPSMA originated from the Technical University of Munich, Germany. Blue Earth Diagnostics acquired exclusive, worldwide rights to rhPSMA imaging technology from Scintomics GmbH in 2018, followed by acquisition of exclusive rights to therapeutic applications in 2020. Blue Earth Diagnostics has two Phase 3 clinical studies evaluating the safety and diagnostic performance of 18F-rhPSMA-7.3 PET imaging in prostate cancer: (“SPOTLIGHT,” NCT04186845), in men with recurrent disease and (“LIGHTHOUSE,” NCT04186819), in men with newly diagnosed prostate cancer. Currently, rhPSMA compounds have not received regulatory approval. About Blue Earth Diagnostics Blue Earth Diagnostics, an indirect subsidiary of Bracco Imaging S.p.A., is a growing international molecular imaging company focused on delivering innovative, well-differentiated diagnostic solutions that inform patient care. Formed in 2014, the Company’s success is driven by its management expertise and supported by a demonstrated track record of rapid development and commercialization of positron emission tomography (PET) radiopharmaceuticals. Blue Earth Diagnostics’ expanding oncology portfolio encompasses a variety of disease states, including prostate cancer and neuro-oncology. Blue Earth Diagnostics is committed to the timely development and commercialization of precision radiopharmaceuticals for potential use in imaging and therapy. About Bracco Imaging S.p.A. Bracco Imaging S.p.A., part of the Bracco Group, is a world-leading diagnostic imaging provider. Headquartered in Milan, Italy, Bracco Imaging develops, manufactures and markets diagnostic imaging agents and solutions. It offers a product and solution portfolio for all key diagnostic imaging modalities: X-ray imaging (including Computed Tomography-CT, Interventional Radiology, and Cardiac Catheterization), Magnetic Resonance Imaging (MRI), Contrast Enhanced Ultrasound (CEUS), and Nuclear Medicine through radioactive tracers and novel PET imaging agents to inform clinical management and guide care for cancer patients in areas of unmet medical need. Our continually evolving portfolio is completed by a range of medical devices, advanced administration systems and dose-management software. In 2019 Bracco Imaging also enriched its product portfolio by expanding the range of oncology nuclear imaging solutions in the urology segment and other specialties with the acquisition of Blue Earth Diagnostics.

The Janssen Pharmaceutical Companies of Johnson & Johnson today announced new real-world evidence data showing the initiation of ERLEADA® (apalutamide) results in high rates of rapid and deep prostate-specific antigen (PSA) response among patients with metastatic castration-sensitive prostate cancer (mCSPC). In a separate post-hoc analysis of the registrational Phase 3 SPARTAN and TITAN studies, rapid and deep PSA responses with ERLEADA® were associated with improvement in patient-reported outcomes (PROs) related to quality of life, physical wellbeing, pain, and fatigue intensity. These findings will be presented during the American Society of Clinical Oncology's Genitourinary (ASCO GU) Cancers Symposium, taking place in San Francisco and virtually from February 17-19, 2022. The real-world evidence study evaluating PSA response (Abstract 43, Poster B9) included data from 186 patients treated with ERLEADA® and 165 treated with enzalutamide from 69 community urology practices in the United States. By six months, 69.3 percent of patients with mCSPC initiated on ERLEADA® attained PSA90 response and 55.6 percent for enzalutamide (HR=1.56; p=0.014). PSA90 response is defined as the patient's earliest attainment of ≥90 percent decline in PSA relative to their baseline PSA at treatment initiation. At nine months and by the end of follow-up, 70.4 percent of patients treated with ERLEADA® achieved PSA90 and 62.5 percent for enzalutamide (HR=1.49; p=0.024). The median time to PSA90 response was 3.1 months for patients treated with ERLEADA® and to 5.2 months for enzalutamide.1* "Deep PSA response is an important early prognostic factor for achieving longer radiographic progression-free survival and overall survival in patients with metastatic castration-sensitive prostate cancer," said Benjamin Lowentritt, M.D., Director Prostate Cancer Care Program, Chesapeake Urology, and Past President, AUA, Mid-Atlantic Region, and lead study investigator.** "These real-world data are consistent with and reinforce the benefit of ERLEADA as reported in the clinical trial setting, providing prescribers with important insights regarding time to and durability of PSA90 responses for commonly prescribed mCSPC medications." Patients included in the analysis had at least 12 months of clinical activity to assess baseline characteristics and were classified into treatment cohorts based on their first filled prescription for ERLEADA® or enzalutamide after Dec. 16, 2019. Patients were followed from their first filled prescription date until the earliest of one of the following events: regimen discontinuation, treatment switch, end of clinical activity or end of data availability (March 5, 2021). A separate ERLEADA® poster presentation evaluating PROs data (Abstract 73, Poster D1) demonstrated an association between rapid and deep PSA decline and improved health-related quality of life PROs as reported from the Phase 3 SPARTAN and TITAN studies. Patient-reported outcomes were assessed using tools including the Functional Assessment of Cancer Therapy-Prostate (FACT-P; TITAN and SPARTAN), Brief Pain Inventory-Short Form (BPI-SF; TITAN only), and Brief Fatigue Inventory (BFI; TITAN only): A landmark analysis at three months after treatment initiation evaluated the association between deep PSA decline (≤ 0.2 ng/mL) and delay in deterioration in PROs (defined as decrease ≥ 10 points FACT-P total, ≥ 3 points Physical Wellbeing, ≥ 30 percent baseline for BPI-SF worst pain, or ≥ 2 points for BFI worst fatigue).2 Patients in both studies who achieved a deep PSA decline maintained FACT-P total (SPARTAN: HR=0.83; TITAN: HR=0.54) or FACT-P Physical Wellbeing (SPARTAN: HR=0.70; TITAN: HR=0.63) levels longer.2 Patients in TITAN who achieved a deep PSA decline had a lower risk of increasing pain or worsening fatigue; as assessed by the BPI-SF worst pain intensity progression (HR=0.70) or BFI worst fatigue intensity progression (HR=0.76), respectively.2 "This analysis demonstrates that the rapid and deep PSA responses shown in the SPARTAN and TITAN pivotal studies translate into improved quality of life for patients," said Tracy McGowan, M.D., Therapeutic Area Head, U.S. Medical Affairs, Janssen Scientific Affairs, LLC. "We are dedicated to continually expanding the body of research for ERLEADA by providing important information that may help patients and their physicians make treatment decisions that work best for them." To date, published results on ERLEADA® include data from more than 2,000 patients across three Phase 3 clinical studies. ERLEADA® has shown a statistically significant improvement in overall survival with a consistent safety profile, while maintaining patients' health-related quality of life in both approved indications of mCSPC and non-metastatic castration resistant prostate cancer (nmCRPC).3 ERLEADA® is currently approved in more than 74 countries. About ERLEADA® ERLEADA® is an androgen receptor inhibitor indicated for the treatment of patients with nmCRPC and for the treatment of patients with mCSPC.4 ERLEADA® received U.S. Food and Drug Administration (FDA) approval for nmCRPC on February 14, 2018 and was approved for mCSPC on September 17, 2019.4 To date, more than 50,000 patients worldwide have been treated with ERLEADA®. ERLEADA® is taken orally, once daily, with or without food.4 The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer include apalutamide (ERLEADA®) with continued androgen deprivation therapy**† as a Category 1 Preferred treatment option for patients with non-metastatic (M0) castration-resistant prostate cancer and a PSADT ≤10 months.4 The NCCN Clinical Practice Guidelines® also include apalutamide (ERLEADA®) with androgen deprivation**† as a Category 1 Preferred 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).***5 ERLEADA® is being further studied in two ongoing Phase 3 clinical trials. *© National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed December 11, 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 †Use of an LHRH agonist plus a first-generation antiandrogen is an option for patients receiving ADT alone, but is not an option for patients receiving apalutamide. ‡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. ERLEADA® IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Cerebrovascular and Ischemic Cardiovascular Events — In a randomized study (SPARTAN) of patients with nmCRPC, ischemic cardiovascular events occurred in 3.7% of patients treated with ERLEADA® and 2% of patients treated with placebo. In a randomized study (TITAN) in patients with mCSPC, ischemic cardiovascular events occurred in 4.4% of patients treated with ERLEADA® and 1.5% of patients treated with placebo. Across the SPARTAN and TITAN studies, 4 patients (0.3%) treated with ERLEADA® and 2 patients (0.2%) treated with placebo died from an ischemic cardiovascular event. Patients with history of unstable angina, myocardial infarction, congestive heart failure, stroke, or transient ischemic attack within 6 months of randomization were excluded from the SPARTAN and TITAN studies. In the SPARTAN study, cerebrovascular events occurred in 2.5% of patients treated with ERLEADA® and 1% of patients treated with placebo. In the TITAN study, cerebrovascular events occurred in 1.9% of patients treated with ERLEADA® and 2.1% of patients treated with placebo. Across the SPARTAN and TITAN studies, 3 patients (0.2%) treated with ERLEADA®, and 2 patients (0.2%) treated with placebo died from a cerebrovascular event. Cerebrovascular and ischemic cardiovascular events, including events leading to death, occurred in patients receiving ERLEADA®. Monitor for signs and symptoms of ischemic heart disease and cerebrovascular disorders. 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 two 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 findings from animals and 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 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% (1.8%), placebo 21% (1.6%) Chemistry — In the TITAN study: hypertriglyceridemia ERLEADA® 17% (2.5%), placebo 12% (2.3%). In the SPARTAN study: hypercholesterolemia ERLEADA® 76% (0.1%), placebo 46% (0%); hyperglycemia ERLEADA® 70% (2%), placebo 59% (1.0%); hypertriglyceridemia ERLEADA® 67% (1.6%), placebo 49% (0.8%); hyperkalemia ERLEADA® 32% (1.9%), placebo 22% (0.5%) Rash — In 2 randomized studies (SPARTAN and TITAN), 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 (SPARTAN and TITAN), hypothyroidism was reported for 8% of patients treated with ERLEADA® and 1.5% 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 CYP3A4, CYP2C9, CYP2C19, and UGT Substrates — 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®. 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.