INTERFERON ALFA-2B(Merck Sharp & Dohme )

BURLINGTON, Mass.--( BUSINESS WIRE )-- PharmaEssentia USA Corporation , a subsidiary of PharmaEssentia Corporation (TWSE: 6446), a global biopharmaceutical innovator based in Taiwan leveraging deep expertise and proven scientific principles to deliver new biologics in hematology and oncology, today announced that the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines ® ) have recently been updated to include ropeginterferon alfa-2b-njft, marketed as BESREMi ® , as a preferred first-line cytoreductive therapy option for the treatment of adults with symptomatic, low-risk polycythemia vera (PV). Ropeginterferon alfa-2b-njft is the only preferred therapeutic option for both high-risk and low-risk (symptomatic) PV regardless of treatment history. 1 “ The recent update to the NCCN Guidelines ® reflects the ongoing shift in PV care towards earlier intervention, focusing on long-term patient health,” said Rami Komrokji, M.D., Vice Chair of the Malignant Hematology Department and Head of the Leukemia and MDS Section at Moffitt Cancer Center. National Comprehensive Cancer Network ® (NCCN ® ) is a well-recognized, not-for-profit alliance of leading cancer centers in the United States. Its treatment practice guidelines, which are reviewed and updated on a continual basis to reflect the most current evidence, are widely respected and followed by the U.S. physician community and serve to inform and facilitate coverage decisions with payers for oncology therapies. Based on its growing body of supporting clinical evidence and broad label, ropeginterferon alfa-2b-njft is now categorized by the latest NCCN Guidelines ® update as a preferred first-line cytoreductive therapy based on NCCN ® ’s determination of superior efficacy, safety and evidence 1 , as well as a category 2A therapy, which means that there is uniform NCCN ® consensus that the intervention is appropriate 1 . The updated NCCN Guidelines ® were released on December 21, 2023. “ This is another important milestone for BESREMi as a preferred, FDA-approved option for both symptomatic low- and high-risk PV patients,” said Albert Qin, M.D., Ph.D., Chief Medical Officer at PharmaEssentia Corporation. “ We are encouraged by the increasing dialogue across academic and community healthcare practitioners rethinking treatment approaches given the potential of BESREMi for this myeloproliferative neoplasm.” About Polycythemia Vera (PV) Polycythemia vera (PV) is a myeloproliferative neoplasm originating from a disease-initiating stem cell in the bone marrow resulting in a chronic increase of red blood cells, white blood cells, and platelets. PV may result in cardiovascular complications such as thrombosis and embolism, and often transforms to secondary myelofibrosis or leukemia. While the molecular mechanism underlying PV is still subject of intense research, current results point to a set of acquired mutations, the most important being a mutant form of JAK2. 2 About BESREMi ® (ropeginterferon alfa-2b-njft) BESREMi is an innovative monopegylated, long-acting interferon. With its unique pegylation technology, BESREMi has a long duration of activity in the body and is aimed to be administered once every two weeks (or every four weeks with hematological stability for at least one year), allowing flexible dosing that helps meet the individual needs of patients. BESREMi has orphan drug designation for the treatment of polycythemia vera (PV) in adults in the United States. The product was approved by the European Medicines Agency (EMA) in 2019, by the US Food and Drug Administration (FDA) in 2021 and has recently received approval in Taiwan and South Korea. The drug candidate was invented by PharmaEssentia and is manufactured in the company’s Taichung plant, which was cGMP certified by TFDA in 2017 and by EMA in January 2018. PharmaEssentia retains full global intellectual property rights for the product in all indications. BESREMi was approved with a boxed warning for risk of serious disorders including aggravation of neuropsychiatric, autoimmune, ischemic and infectious disorders. Please see full Prescribing Information , including Boxed Warning. Indication BESREMi is indicated for the treatment of adults with polycythemia vera. Important Safety Information WARNING: RISK OF SERIOUS DISORDERS Interferon alfa products may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping therapy. CONTRAINDICATIONS Existence of, or history of severe psychiatric disorders, particularly severe depression, suicidal ideation, or suicide attempt Hypersensitivity to interferons including interferon alfa-2b or any of the inactive ingredients of BESREMi. Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment History or presence of active serious or untreated autoimmune disease Immunosuppressed transplant recipients WARNINGS AND PRECAUTIONS Depression and Suicide: Life-threatening or fatal neuropsychiatric reactions have occurred in patients receiving interferon alfa-2b products, including BESREMi. These reactions may occur in patients with and without previous psychiatric illness. Other central nervous system effects, including suicidal ideation, attempted suicide, aggression, bipolar disorder, mania and confusion have been observed with other interferon alfa products. Closely monitor patients for any symptoms of psychiatric disorders and consider psychiatric consultation and treatment if such symptoms emerge. If psychiatric symptoms worsen, it is recommended to discontinue BESREMi therapy. Endocrine Toxicity: These toxicities may include worsening hypothyroidism and hyperthyroidism. Do not use BESREMi in patients with active serious or untreated endocrine disorders associated with autoimmune disease. Evaluate thyroid function in patients who develop symptoms suggestive of thyroid disease during BESREMi therapy. Discontinue BESREMi in patients who develop endocrine disorders that cannot be adequately managed during treatment with BESREMi. Cardiovascular Toxicity: Toxicities may include cardiomyopathy, myocardial infarction, atrial fibrillation and coronary artery ischemia. Patients with a history of cardiovascular disorders should be closely monitored for cardiovascular toxicity during BESREMi therapy. Avoid use of BESREMi in patients with severe or unstable cardiovascular disease, (e.g., uncontrolled hypertension, congestive heart failure (≥ NYHA class 2), serious cardiac arrhythmia, significant coronary artery stenosis, unstable angina) or recent stroke or myocardial infarction. Decreased Peripheral Blood Counts: These toxicities may include thrombocytopenia (increasing the risk of bleeding), anemia, and leukopenia (increasing the risk of infection). Monitor complete blood counts at baseline, during titration and every 3-6 months during the maintenance phase. Monitor patients for signs and symptoms of infection or bleeding. Hypersensitivity Reactions: Toxicities may include serious, acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis). If such reactions occur, discontinue BESREMi and institute appropriate medical therapy immediately. Transient rashes may not necessitate interruption of treatment. Pancreatitis: Pancreatitis has occurred in 2.2% of patients receiving BESREMi. Symptoms may include nausea, vomiting, upper abdominal pain, bloating, and fever. Patients may experience elevated lipase, amylase, white blood cell count, or altered renal/hepatic function. Interrupt BESREMi treatment in patients with possible pancreatitis and evaluate promptly. Consider discontinuation of BESREMi in patients with confirmed pancreatitis. Colitis: Fatal and serious ulcerative or hemorrhagic/ischemic colitis have occurred in patients receiving interferon alfa products, some cases starting as early as 12 weeks after start of treatment. Symptoms may include abdominal pain, bloody diarrhea, and fever. Discontinue BESREMi in patients who develop these signs or symptoms. Colitis may resolve within 1 to 3 weeks of stopping treatment. Pulmonary Toxicity: Pulmonary toxicity may manifest as dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension, and sarcoidosis. Some events have resulted in respiratory failure or death. Discontinue BESREMi in patients who develop pulmonary infiltrates or pulmonary function impairment. Ophthalmologic Toxicity: These toxicities may include severe eye disorders such as retinopathy, retinal hemorrhage, retinal exudates, retinal detachment and retinal artery or vein occlusion which may result in blindness. During BESREMi therapy, 23% of patients were identified with an eye disorder. Eyes disorders ≥5% included cataract (6%) and dry eye (5%). Advise patients to have eye examinations before and during BESREMi therapy, specifically in those patients with a retinopathy-associated disease such as diabetes mellitus or hypertension. Evaluate eye symptoms promptly. Discontinue BESREMi in patients who develop new or worsening eye disorders. Hyperlipidemia: Elevated triglycerides may result in pancreatitis. Monitor serum triglycerides before BESREMi treatment and intermittently during therapy and manage when elevated. Consider discontinuation of BESREMi in patients with persistently, markedly elevated triglycerides. Hepatotoxicity: These toxicities may include increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) and bilirubin. Liver enzyme elevations have also been reported in patients after long-term BESREMi therapy. Monitor liver enzymes and hepatic function at baseline and during BESREMi treatment. Discontinue BESREMi in patients who develop evidence of hepatic decompensation (characterized by jaundice, ascites, hepatic encephalopathy, hepatorenal syndrome or variceal hemorrhage) during treatment. Renal Toxicity: Monitor serum creatinine at baseline and during therapy. Avoid use of BESREMi in patients with eGFR <30 mL/min. Discontinue BESREMi if severe renal impairment develops during treatment. Dental and Periodontal Toxicity: These toxicities may include dental and periodontal disorders, which may lead to loss of teeth. In addition, dry mouth could have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with BESREMi. Patients should have good oral hygiene and regular dental examinations. Dermatologic Toxicity: These toxicities have included skin rash, pruritus, alopecia, erythema, psoriasis, xeroderma, dermatitis acneiform, hyperkeratosis, and hyperhidrosis. Consider discontinuation of BESREMi if clinically significant dermatologic toxicity occurs. Driving and Operating Machinery: BESREMi may impact the ability to drive and use machinery. Patients should not drive or use heavy machinery until they know how BESREMi affects their abilities. Patients who experience dizziness, somnolence or hallucination during BESREMi therapy should avoid driving or using machinery. Embryo-Fetal Toxicity: Based on the mechanism of action, BESREMi can cause fetal harm when administered to a pregnant woman. Pregnancy testing is recommended in females of reproductive potential prior to treatment with BESREMi. Advise females of reproductive potential to use an effective method of contraception during treatment with BESREMi and for at least 8 weeks after the final dose. ADVERSE REACTIONS The most common adverse reactions reported in > 40% of patients in the PEGINVERA study (n=51) were influenza-like illness, arthralgia, fatigue, pruritis, nasopharyngitis, and musculoskeletal pain. In the pooled safety population (n=178), the most common adverse reactions greater than 10%, were liver enzyme elevations (20%), leukopenia (20%), thrombocytopenia (19%), arthralgia (13%), fatigue (12%), myalgia (11%), and influenza-like illness (11%). DRUG INTERACTIONS Patients on BESREMi who are receiving concomitant drugs which are CYP450 substrates with a narrow therapeutic index should be monitored to inform the need for dosage modification for these concomitant drugs. Avoid use with myelosuppressive agents and monitor patients receiving the combination for effects of excessive myelosuppression. Avoid use with narcotics, hypnotics or sedatives and monitor patients receiving the combination for effects of excessive CNS toxicity. USE IN SPECIFIC POPULATIONS Pregnancy: Based on mechanism of action and the role of interferon alfa in pregnancy and fetal development, BESREMi may cause fetal harm and should be assumed to have abortifacient potential when administered to a pregnant woman. There are adverse effects on maternal and fetal outcomes associated with polycythemia vera in pregnancy. Advise pregnant women of the potential risk to a fetus. Lactation: There are no data on the presence of BESREMi in human or animal milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children from BESREMi, advise women not to breastfeed during treatment and for 8 weeks after the final dose. Females of Reproductive Potential: BESREMi may cause embryo-fetal harm when administered to a pregnant woman. Pregnancy testing prior to BESREMi treatment is recommended for females of reproductive potential. Advise female patients of reproductive potential to use effective contraception during treatment with BESREMi and for at least 8 weeks after the final dose. Pediatric Use: Safety and effectiveness in pediatric patients have not been established. Geriatric Use: In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other therapy. About PharmaEssentia PharmaEssentia (TWSE: 6446), headquartered in Taipei, Taiwan, is a global and rapidly growing biopharmaceutical innovator. Leveraging deep expertise and proven scientific principles, PharmaEssentia aims to deliver effective new biologics for challenging diseases in the areas of hematology, oncology, and immunology with one approved product and a diversifying pipeline. Founded in 2003 by a team of Taiwanese-American executives and renowned scientists from U.S. biotechnology and pharmaceutical companies, today PharmaEssentia is expanding its global presence with operations in the U.S., Japan, China, and Korea, along with a world-class biologics production facility in Taichung, Taiwan. For more information about PharmaEssentia USA, visit the website , LinkedIn or Twitter . Forward Looking Statement This press release contains forward looking statements, including statements regarding our pipeline, research and development efforts, and market opportunity for our products. For those statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995 and similar legislation and regulations under Taiwanese law. These forward-looking statements are based on management expectations and assumptions as of the date of this press release, and actual results may differ materially from those in these forward-looking statements as a result of various factors. These factors include risks and uncertainties related to the initiation, timing, progress and results of our research and development programs, preclinical studies, clinical trials, regulatory submissions, commercialization plans, customer and prescriber patterns or practices, and reimbursement activities and outcomes. Any forward-looking statements set forth in this press release speak only as of the date of this press release. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. © 2024 PharmaEssentia Corporation. All rights reserved. PharmaEssentia, the PharmaEssentia logo, and BESREMi are trademarks or registered trademarks of PharmaEssentia Corporation. 1 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Myeloproliferative Neoplasms V.1.2024. © National Comprehensive Cancer network, Inc. 2023. All rights reserved. Accessed Jan 22, 2024. To view the most recent and complete version of the guideline, 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. 2 Cerquozzi S, Tefferi A. Blast transformation and fibrotic progression in polycythemia vera and essential thrombocythemia: a literature review of incidence and risk factors. Blood Cancer J . 2015;5, e366; DOI:10.1038/bcj.2015.95

PARSIPPANY, N.J.--( BUSINESS WIRE )--Ferring Pharmaceuticals today announced that ADSTILADRIN ® (nadofaragene firadenovec-vncg) is now fully available across the U.S. for healthcare providers to prescribe for their adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. Approved by the U.S. Food & Drug Administration (FDA) in December 2022, ADSTILADRIN is the first and only FDA-approved intravesical gene therapy for adults with NMIBC who no longer respond to standard therapy. “From the day we received FDA approval, Ferring has been committed to making ADSTILADRIN available to every appropriate high-risk NMIBC patient quickly and responsibly, working collaboratively with the bladder cancer community to inform our approach,” said Bipin Dalmia, Senior Vice President, Global Head, Uro-Oncology Franchise at Ferring Pharmaceuticals. “With our significant manufacturing investments, we have achieved full product supply ahead of schedule. We are therefore ending our ADSTILADRIN Early Experience Program and look forward to bringing this novel therapy to every patient who needs it.” In September 2023, Ferring initiated the ADSTILADRIN Early Experience Program to a mix of clinical trial sites that participated in the ADSTILADRIN Phase 3 study and community clinics with the highest number of appropriate patients with NMIBC. This temporary program represented Ferring’s commitment to treat as many patients as possible in the short term while ensuring every patient who started on ADSTILADRIN had the ability to continue therapy for the duration of their treatment. Now that full product supply is available ahead of schedule, Ferring can end the temporary ADSTILADRIN Early Experience Program and dramatically increase patient access. “ADSTILADRIN represents an effective alternative therapy for patients with NMIBC who, historically, had very few options once they no longer responded to standard BCG therapy,” said Andrea Maddox-Smith, CEO of the Bladder Cancer Advocacy Network, BCAN. “Increasing access to this innovative therapy offers the potential of what patients need most – safe, effective treatment options that bring hope.” Ferring also initiated a non-interventional study, known as the “ADSTILADRIN in BLadder CancEr” (ABLE-41) U.S. Real World Evidence (RWE) Study (NCT06026332). This ongoing study is exploring early utilization, experiences, and outcomes of ADSTILADRIN in the routine care setting. About ADSTILADRIN ADSTILADRIN® (nadofaragene firadenovec-vncg) is the first and only FDA-approved intravesical gene-therapy for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. It is a non-replicating adenovirus vector-based therapy containing the gene interferon alfa-2b, administered by catheter directly into the bladder once every three months. The vector enters the cells of the bladder wall, releasing the active gene and causing the bladder’s cell walls to secrete high quantities of interferon alfa-2b protein, a naturally-occurring protein the body uses to fight cancer. This approach essentially turns the bladder wall cells into interferon microfactories, enhancing the body’s own natural defenses against the cancer. ADSTILADRIN has been studied in a clinical trial program that includes 157 patients with high-grade, BCG-unresponsive NMIBC who had been treated with adequate BCG previously and did not see benefit from additional BCG treatment (full inclusion criteria published on clinicaltrials.gov: NCT02773849). 1 About Non-Muscle Invasive Bladder Cancer (NMIBC) NMIBC is a form of bladder cancer which is present in the superficial layer of the bladder and has not invaded deeper into the bladder or spread to other parts of the body. 2 Bladder cancer is the sixth most common cancer in the U.S., and it is estimated that there were approximately 81,180 new cases of bladder cancer in the U.S. in 2022, 3 75% of which present as NMIBC. 4 In patients with high-risk NMIBC, intravesical BCG remains the first-line standard of care. However, more than 50% of patients who receive initial treatment with BCG will experience disease recurrence and progression within one year, with many developing BCG-unresponsive disease. 3 Current treatment options for BCG-unresponsive patients are very limited, and National Comprehensive Cancer Network (NCCN) guidelines recommend cystectomy (partial or complete removal of the bladder). 5 INDICATION ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy indicated for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS: ADSTILADRIN is contraindicated in patients with prior hypersensitivity reactions to interferon alfa or to any component of the product. WARNINGS AND PRECAUTIONS: Risk with delayed cystectomy: Delaying cystectomy in patients with BCG-unresponsive CIS could lead to development of muscle invasive or metastatic bladder cancer, which can be lethal. If patients with CIS do not have a complete response to treatment after 3 months or if CIS recurs, consider cystectomy. Risk of disseminated adenovirus infection: Persons who are immunocompromised or immunodeficient may be at risk for disseminated infection from ADSTILADRIN due to low levels of replication-competent adenovirus. Avoid ADSTILADRIN exposure to immunocompromised or immunodeficient individuals. DOSAGE AND ADMINISTRATION: Administer ADSTILADRIN by intravesical instillation only. ADSTILADRIN is not for intravenous use, topical use, or oral administration. USE IN SPECIFIC POPULATIONS: Advise females of reproductive potential to use effective contraception during ADSTILADRIN treatment and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during ADSTILADRIN treatment and for 3 months after the last dose. ADVERSE REACTIONS: The most common (>10%) adverse reactions, including laboratory abnormalities (>15%), were glucose increased, instillation site discharge, triglycerides increased, fatigue, bladder spasm, micturition (urination urgency), creatinine increased, hematuria (blood in urine), phosphate decreased, chills, pyrexia (fever), and dysuria (painful urination). You are encouraged to report negative side effects of prescription drugs to FDA. Visit www.FDA.gov/medwatch or call 1-800-332-1088. You may also contact Ferring Pharmaceuticals at 1-888-FERRING. Please click to see the full Prescribing Information . About Ferring Pharmaceuticals Ferring Pharmaceuticals is a research-driven, specialty biopharmaceutical group committed to helping people around the world build families and live better lives. In the United States, Ferring is a leader in reproductive medicine and maternal health, uro-oncology and in specialty areas within gastroenterology, including microbiome therapeutics, and orthopaedics. For more information, call 1-888-FERRING (1-888-337-7464) or visit http://www.ferringusa.com/ . References: ADSTILADRIN in Patients With High Grade, Bacillus Calmette-Guerin (BCG) Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC). Gov Identifier: NCT02773849. https://clinicaltrials.gov/ct2/show/NCT02773849 . Boorjian SA, Alemozaffar M, Konety BR, et al. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Lancet Oncol 2021; 22: 107–17. American Cancer Society. Key Statistics for Bladder Cancer. https://www.cancer.org/cancer/bladder-cancer/about/key-statistics.html . Updated January 13,2023. Accessed October 15, 2023. Burger M, Catto JW, Dalbagni G, et al. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013;63(2):234-41. NCCN Guideline Insights. Bladder Cancer, Version 3.2023. www.nccn.org/patients/guidelines/content/PDF/bladder-patient.pdf . Accessed November 7, 2023. More information is available at the following: Health Care Providers: If you are interested in ordering ADSTILADRIN, please sign up for information and updates at ADSTILADRINHCP.com . Patients and Consumers: For more information about ADSTILADRIN, please call 1-888-FERRING (888-337-7464), and select option number one.