Pulmonary Veno-Occlusive Disease

FDA-approved generic provides cost-effective option for treating cancer LAKE ZURICH, Ill.--(BUSINESS WIRE)-- Fresenius Kabi announced today it has introduced Cyclophosphamide for Injection, USP, a generic substitute for Cytoxan, for use in treating several forms of cancer. Now available in the U.S., Cyclophosphamide for Injection, USP is the newest addition to Fresenius Kabi’s broad portfolio of generic oncology injectables that help make cancer therapies more affordable and accessible. This press release features multimedia. View the full release here: Cyclophosphamide is now available from Fresenius Kabi. (Photo: Business Wire) “The introduction of Cyclophosphamide for Injection adds another critical treatment to our broad and leading oncology portfolio that offers lower-cost options for treating cancer,” said John Ducker, president and CEO of Fresenius Kabi USA. Supplied as a 500mg, 1g, and 2g single-dose vials of lyophilized powder, the drug can be administered intravenously or orally. Fresenius Kabi offers all lyophilized presentations of cyclophosphamide currently in the market. Cyclophosphamide for Injection, USP is available through distributors or direct from Fresenius Kabi. About Cyclophosphamide for Injection, USP Cyclophosphamide for Injection is an alkylating drug indicated for the treatment of: Malignant Diseases: malignant lymphomas: Hodgkin's disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt's lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma Minimal Change Nephrotic Syndrome in Pediatric Patients: biopsy proven minimal change nephrotic syndrome patients who failed to adequately respond to or are unable to tolerate adrenocorticosteroid therapy Limitations of Use: The safety and effectiveness for the treatment of nephrotic syndrome in adults or other renal disease has not been established. IMPORTANT SAFETY INFORMATION Cyclophosphamide for Injection is contraindicated in patients with hypersensitivity to cyclophosphamide and with urinary outflow obstruction. Myelosuppression, Immunosuppression, Bone Marrow Failure and Infections - Severe immunosuppression may lead to serious and sometimes fatal infections. Close hematological monitoring is required. Urinary Tract and Renal Toxicity - Hemorrhagic cystitis, pyelitis, ureteritis, and hematuria can occur. Exclude or correct any urinary tract obstructions prior to treatment. Cardiotoxicity - Myocarditis, myopericarditis, pericardial effusion, arrhythmias and congestive heart failure, which may be fatal, have been reported. Monitor patients, especially those with risk factors for cardiotoxicity or pre-existing cardiac disease. Pulmonary Toxicity - Pneumonitis, pulmonary fibrosis and pulmonary veno-occlusive disease leading to respiratory failure may occur. Monitor patients for signs and symptoms of pulmonary toxicity. Secondary malignancies have been reported in patients treated with cyclophosphamide-containing regimens. Veno-occlusive Liver Disease - Fatal outcome can occur. Embryo-Fetal Toxicity - Can cause fetal harm. Advise female patients of reproductive potential to avoid pregnancy. Adverse reactions reported most often include neutropenia, febrile neutropenia, fever, alopecia, nausea, vomiting, and diarrhea. To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176, option 5, or FDA at 1-800-FDA-1088 or . Nursing Mothers: Discontinue drug or nursing. Females and males of reproductive potential: Counsel patients on pregnancy prevention and planning. Renal Patients: Monitor for toxicity in patients with moderate and severe renal impairment. This Important Safety Information does not include all the information needed to use Cyclophosphamide for Injection, USP safely and effectively. Please see the full prescribing information for Cyclophosphamide for Injection, USP at . About Fresenius Kabi Fresenius Kabi ( ) is a global health care company that specializes in injectable medicines, biosimilars, clinical nutrition and technologies for infusion and transfusion. The company’s products and services are used to help care for patients with critical and chronic conditions. The company’s U.S. headquarters is in Lake Zurich, Illinois. The company’s global headquarters is in Bad Homburg, Germany. To learn about U.S. career opportunities at Fresenius Kabi, visit us at and follow us on LinkedIn and Facebook.

Study findings presented during the American College of Cardiology's 72nd Annual Scientific Session & Expo Together With World Heart Federation's World Congress of Cardiology European Society of Cardiology/European Respiratory Society (ESC/ERS) PH guidelines recommend initial dual combination therapy with macitentan and tadalafil for PAH patients without cardiopulmonary comorbidities RARITAN, N.J., March 6, 2023 /PRNewswire/ -- The Janssen Pharmaceutical Companies of Johnson & Johnson today announced results from the Phase 3 A DUE study (NCT03904693), which showed an investigational once-daily, single tablet combination therapy, also known as fixed dose combination, of macitentan 10 mg and tadalafil 40 mg (M/T STCT), significantly improved pulmonary hemodynamics (blood flow through pulmonary blood vessels) versus macitentan and tadalafil monotherapies in pulmonary arterial hypertension (PAH) patients with World Health Organization (WHO) functional class (FC) II or III.1 The data were presented today as a Late-Breaking Clinical Trial presentation during the American College of Cardiology's 72nd Annual Scientific Session & Expo Together With World Heart Federation's World Congress of Cardiology. PAH is a rare, progressive and life-threatening blood vessel disorder characterized by the constriction of small pulmonary arteries and elevated blood pressure in the pulmonary circulation that eventually leads to right heart failure.2 Recently updated European Society of Cardiology/European Respiratory Society (ESC/ERS) PH guidelinesi have recommended initial dual combination therapy with macitentan and tadalafil for PAH patients without cardiopulmonary comorbidities. Currently, this requires patients to take multiple pills as no single tablet that combines two or more PAH-specific pathways is available for these patients.3 "Targeting different pathways in the treatment of PAH has demonstrated clear clinical benefits, yet current treatment regimens are cumbersome and create a significant pill burden for patients, many of whom take a large number of pills each day to treat their PAH and various co-morbidities,ii,iii" said Kelly Chin, M.D., Professor of Internal Medicine and Director of the Pulmonary Hypertension Program at UT Southwestern Medical Center, and an investigator in the A DUE study.4 "The results from this study demonstrate that a single tablet combination has the potential to support initial dual combination therapy and rapid escalation from monotherapy, which may improve functional outcomes and help close the gap from guideline recommendations to clinical practice." The A DUE study is a double-blind, randomized, active-controlled, multi-center, adaptive parallel-group study designed to compare the efficacy and safety of investigational M/T STCT versus macitentan and tadalafil monotherapies in patients with PAH. A total of 187 adult PAH patients from across 148 sites in 19 countries worldwide in WHO FC II or III who were treatment naïve or on a stable dose of an endothelin receptor antagonist (ERA) or a phosphodiesterase type 5 inhibitor (PDE5i) for at least three months, were enrolled in the study. The primary endpoint is pulmonary vascular resistance (PVR) measured 16 weeks following initiation of treatment expressed as the ratio of geometric means to baseline. Secondary efficacy outcome measures included change from baseline in exercise capacity as measured by change in 6-minute walk distance (6MWD) at the end of double-blind treatment at week 16 compared to baseline. Following the double-blind treatment period, patients transitioned to the open-label treatment period for 24 months. Baseline characteristics were balanced across treatment arms except for a higher proportion of WHO FC II patients in the M/T STCT arm and a greater time from diagnosis of PAH in the macitentan arm. "The guiding light of our PH research is the goal of transforming PAH into a manageable condition, so we're constantly looking for ways to improve both clinical outcomes and the treatment experience," said James List, M.D., Ph.D., Global Therapeutic Area Head, Cardiovascular, Metabolism, Retina & Pulmonary Hypertension, Janssen Research & Development, LLC. "A single tablet combination has the potential to be an important new option for helping physicians optimize disease management with the potential to enhance convenience and help improve adherence and outcomes." Key A DUE Study Findings The A DUE study met its co-primary endpoint, demonstrating marked pulmonary hemodynamic improvement as shown by the highly statistically significant, consistent and robust PVR reduction in participants treated with M/T STCT compared to both monotherapies. PVR change with M/T STCT was significantly greater versus macitentan (treatment effect: 29%; 95% confidence limit [CL]: -18%, -39%, p<0.0001). PVR change with M/T STCT was also significantly greater versus tadalafil (treatment effect: 28%; 95% CL: -20%, -36%, p<0.0001). Although the A DUE study was not powered to demonstrate a benefit on exercise capacity, there was a clinically relevant improvement in 6MWD. At week 16, treatment effect was not statistically significant; however, a clinically relevant improvement in 6MWD in favor of M/T STCT versus monotherapies was observed. Adjusted treatment effect in 6MWD, change from baseline, in the M/T STCT versus macitentan group was 16.04m (CL: -17.0, 49.08, p=0.380) and 25.37m in the M/T STCT versus tadalafil group (CL: -0.93, 51.59, p =0.059). The safety profile of M/T STCT was consistent with the known safety profiles of macitentan and tadalafil monotherapies and no new safety observations were made. About macitentan/tadalafil STCT Macitentan 10 mg and tadalafil 40 mg STCT is an investigational therapy that combines the ERA, macitentan, and the PDE5i, tadalafil. About OPSUMIT ® (macitentan) OPSUMIT® is indicated for the treatment of PAH (WHO Group I) to reduce the risks of disease progression and hospitalization for PAH. The use of OPSUMIT® in patients with PAH (WHO Group I), a type of PH, was demonstrated in the pivotal SERAPHIN trial, the largest (n=742) long-term (average treatment duration=2 years) outcomes-based trial of an ERA in PAH. About tadalafil Tadalafil is indicated for the treatment of PAH (WHO Group 1) to improve exercise ability. Studies establishing effectiveness included predominately patients with NYHA Functional Class II – III symptoms and etiologies of idiopathic or heritable PAH (61%) or PAH associated with connective tissue diseases (23%). OPSUMIT® INDICATION AND IMPORTANT SAFETY INFORMATION INDICATION OPSUMIT® (macitentan) is an endothelin receptor antagonist (ERA) indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to reduce the risks of disease progression and hospitalization for PAH. Effectiveness was established in a long-term study in PAH patients with predominantly WHO Functional Class II-III symptoms treated for an average of 2 years. Patients had idiopathic and heritable PAH (57%), PAH caused by connective tissue disorders (31%), and PAH caused by congenital heart disease with repaired shunts (8%). IMPORTANT SAFETY INFORMATION BOXED WARNING: EMBRYO-FETAL TOXICITY Do not administer OPSUMIT® to a pregnant female because it may cause fetal harm. Females of reproductive potential: Exclude pregnancy before the start of treatment, monthly during treatment, and 1 month after stopping treatment. Prevent pregnancy during treatment and for one month after stopping treatment by using acceptable methods of contraception. For all female patients, OPSUMIT® is available only through a restricted program called the OPSUMIT® Risk Evaluation and Mitigation Strategy (REMS). CONTRAINDICATIONS Pregnancy: OPSUMIT® may cause fetal harm when administered to a pregnant woman. OPSUMIT® is contraindicated in females who are pregnant. If OPSUMIT® is used during pregnancy, advise the patient of the potential risk to a fetus. Hypersensitivity: OPSUMIT® is contraindicated in patients with a history of a hypersensitivity reaction to macitentan or any component of the product. WARNINGS AND PRECAUTIONS Embryo-fetal Toxicity and OPSUMIT® REMS Program Due to the risk of embryo-fetal toxicity, OPSUMIT® is available for females only through a restricted program called the OPSUMIT® REMS Program. For females of reproductive potential, exclude pregnancy prior to initiation of therapy, ensure use of acceptable contraceptive methods, and obtain monthly pregnancy tests. Notable requirements of the OPSUMIT® REMS Program include: Prescribers must be certified with the program by enrolling and completing training. All females, regardless of reproductive potential, must enroll in the OPSUMIT® REMS Program prior to initiating OPSUMIT®. Male patients are not enrolled in the REMS. Females of reproductive potential must comply with the pregnancy testing and contraception requirements. Pharmacies must be certified with the program and must only dispense to patients who are authorized to receive OPSUMIT®. Hepatotoxicity ERAs have caused elevations of aminotransferases, hepatotoxicity, and liver failure. The incidence of elevated aminotransferases in the SERAPHIN study >3 x ULN was 3.4% for OPSUMIT® vs 4.5% for placebo, and >8 x ULN was 2.1% vs 0.4%, respectively. Discontinuations for hepatic adverse events were 3.3% for OPSUMIT® vs 1.6% for placebo. Obtain liver enzyme tests prior to initiation of OPSUMIT® and repeat during treatment as clinically indicated. Advise patients to report symptoms suggesting hepatic injury (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching). If clinically relevant aminotransferase elevations occur, or if elevations are accompanied by an increase in bilirubin >2 x ULN, or by clinical symptoms of hepatotoxicity, discontinue OPSUMIT®. Consider re-initiation of OPSUMIT® when hepatic enzyme levels normalize in patients who have not experienced clinical symptoms of hepatotoxicity. Fluid Retention Peripheral edema and fluid retention are known consequences of PAH and ERAs. In the pivotal PAH study SERAPHIN, edema was reported in 21.9% of the OPSUMIT® group vs 20.5% for placebo. Patients with underlying left ventricular dysfunction may be at particular risk for developing significant fluid retention after initiation of ERA treatment. In a small study of pulmonary hypertension due to left ventricular dysfunction, more patients in the OPSUMIT® group developed significant fluid retention and had more hospitalizations due to worsening heart failure compared to placebo. Postmarketing cases of edema and fluid retention occurring within weeks of starting OPSUMIT®, some requiring intervention with a diuretic or hospitalization for decompensated heart failure, have been reported. Monitor for signs of fluid retention after OPSUMIT® initiation. If clinically significant fluid retention develops, evaluate the patient to determine the cause and the possible need to discontinue OPSUMIT®. Hemoglobin Decrease Decreases in hemoglobin concentration and hematocrit have occurred following administration of other ERAs and in clinical studies with OPSUMIT®. These decreases occurred early and stabilized thereafter. In the SERAPHIN study, OPSUMIT® caused a mean decrease in hemoglobin (from baseline to 18 months) of about 1.0 g/dL vs no change in the placebo group. A decrease in hemoglobin to below 10.0 g/dL was reported in 8.7% of the OPSUMIT® group vs 3.4% for placebo. Decreases in hemoglobin seldom require transfusion. Initiation of OPSUMIT® is not recommended in patients with severe anemia. Measure hemoglobin prior to initiation of treatment and repeat during treatment as clinically indicated. Pulmonary Edema with Pulmonary Veno-occlusive Disease (PVOD) Should signs of pulmonary edema occur, consider the possibility of associated PVOD. If confirmed, discontinue OPSUMIT®. Decreased Sperm Counts OPSUMIT®, like other ERAs, may have an adverse effect on spermatogenesis. Counsel men about potential effects on fertility. ADVERSE REACTIONS Most common adverse reactions (more frequent than placebo by ≥3%) were anemia (13% vs 3%), nasopharyngitis/pharyngitis (20% vs 13%), bronchitis (12% vs 6%), headache (14% vs 9%), influenza (6% vs 2%), and urinary tract infection (9% vs 6%). DRUG INTERACTIONS Strong inducers of CYP3A4 such as rifampin significantly reduce macitentan exposure. Concomitant use of OPSUMIT® with strong CYP3A4 inducers should be avoided. Strong inhibitors of CYP3A4 like ketoconazole approximately double macitentan exposure. Many HIV drugs like ritonavir are strong inhibitors of CYP3A4. Avoid concomitant use of OPSUMIT® with strong CYP3A4 inhibitors. Use other PAH treatment options when strong CYP3A4 inhibitors are needed as part of HIV treatment. Moderate dual inhibitors of CYP3A4 and CYP2C9 such as fluconazole and amiodarone are predicted to increase macitentan exposure. Avoid concomitant use of OPSUMIT® with moderate dual inhibitors of CYP3A4 and CYP2C9. Concomitant treatment of both a moderate CYP3A4 inhibitor and moderate CYP2C9 inhibitor with OPSUMIT® should also be avoided. Please see full Prescribing Information , including BOXED WARNING. 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 & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension. Learn more at . Follow us at @JanssenGlobal and @JanssenUS. Janssen Research & Development, LLC is part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of macitentan/tadalafil STCT. 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 and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 1, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at , or on request from Johnson & Johnson. None of 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 WHO FC II/III is defined as slight or marked limitation of physical activity with ordinary or less than ordinary activity causing undue shortness of breath or fatigue, chest pain, or near fainting. 2 Right heart failure occurs when the heart's right ventricle is too weak to pump enough blood to the lungs. 3 OPSYNVI® (macitentan 10 mg and tadalafil 40 mg) was approved in Canada in October 2021 and in Argentina in October 2022 but only for substitution indication (for PAH patients who are already treated with combination of macitentan 10 mg and tadalafil 40 mg as separate tablets). 4 Dr. Chin was compensated for her participation on the steering committee for the A DUE study. i 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. European Heart Journal (2022) 43, 3618–3731. . ii Grady D, et al. Pulm Circ 2018; 8:1–9; 6. iii Lauffenburger JC, et al. J Gen Intern Med 2017. Me d i a Contact: Jennifer Silvent Phone: +1 973-479-9845 [email protected] Shelly Orlacchio Phone: +1 717-471-3888 [email protected] Investor C on t ac t : Raychel Kruper Phone: +1 732-524-6164 [email protected] SOURCE Janssen Pharmaceutical Companies of Johnson & Johnson

FARMVILLE, N.C., Oct. 24, 2022 /PRNewswire/ -- CMP Pharma announced today that Tadliq ® (Tadalafil) Oral Suspension, 20 mg/5 mL, the first and only FDA-approved oral liquid suspension of tadalafil, is now available. Tadliq is the first and only FDA-approved liquid oral suspension of tadalafil for adult patients with difficulty swallowing. Tadliq is indicated for the treatment of pulmonary arterial hypertension and ensures consistent dosing. FDA-approved Tadliq addresses the inconsistencies that come from unapproved crushed or compounded tablets and removes the need for complex preparation of powder formulations. Tadliq has a mild peppermint flavor and is available in 150 mL bottles with a 24-month shelf life. "Tadliq is for patients who need treatment but have difficulty swallowing tablets. This product is a nice addition to our portfolio of cardiovascular liquids for this specific patient population which is often ignored", said Gerald Sakowski, CEO of CMP Pharma, Inc. Tadliq is available through three preferred specialty pharmacies and selected wholesalers. CMP Pharma also supports physicians and patients through the CMP Support Services program. Support service representatives are available Monday through Friday from 8 AM to 5 PM EST by contacting the program at 1-844-267-0001. Tadliq (Tadalafil) Oral Suspension is now available. For more information, contact CMP Pharma at 252-753-7111 or visit tadliq.com. About Tadliq Tadliq is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability. Studies establishing effectiveness included predominately patients with NYHA Functional Class II – III symptoms and etiologies of idiopathic or heritable PAH (61%) or PAH associated with connective tissue diseases (23%). Tadliq is contraindicated in patients who are using any form of organic nitrate, either regularly or intermittently. About CMP Pharma, Inc. CMP Pharma is a specialty pharmaceutical company that addresses critical needs for niche markets by developing and manufacturing a portfolio of high value pharmaceutical products, including oral liquids and semi-solids. CMP Pharma combines decades of experience in pharmaceutical development and manufacturing to provide medicines to fill the unmet medical needs of many patients. Important Safety Information Indications and Usage TADLIQ® is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability. Studies establishing effectiveness included predominately patients with NYHA Functional Class II – III symptoms and etiologies of idiopathic or heritable PAH (61%) or PAH associated with connective tissue diseases (23%). Contraindications Concomitant organic nitrates Concomitant Guanylate Cyclase (GC) Stimulators History of known serious hypersensitivity reaction to TADLIQ, ADCIRCA® or CIALIS® Warnings and Precautions Hypotension: Carefully consider whether patients with certain underlying cardiovascular disease could be adversely affected by vasodilatory effects of TADLIQ. Not recommended in patients with pulmonary veno-occlusive disease. Effects on the eye: Sudden loss of vision could be a sign of non-arteritic ischemic optic neuropathy (NAION) and may be permanent. Hearing impairment: Cases of sudden decrease or loss of hearing have been reported with tadalafil. Concomitant PDE5 inhibitors: Avoid use with CIALIS, ADCIRCA or other PDE5 inhibitors. Prolonged erection: Advise patients to seek emergency treatment if an erection lasts >4 hours. To report SUSPECTED ADVERSE REACTIONS, contact CMP Pharma, Inc. at 1-844-321-1443 or FDA at 1-800-FDA-1088 or . Drug Interactions Nitrates: Administration of nitrates within 48 hours after the last dose of TADLIQ is contraindicated Alpha-Blockers: PDE5 inhibitors, including TADLIQ, and alpha-adrenergic blocking agents are both vasodilators with blood- pressure-lowering effects. Antihypertensives: PDE5 inhibitors, including TADLIQ, are mild systemic vasodilators. Alcohol: Both alcohol and tadalafil, a PDE5 inhibitor, act as mild vasodilators. CYP3A Inhibitors/Inducers: Ritonavir, Potent Inhibitors of CYP3A, Potent Inducers of CYP3A Dosage and Administration The recommended dose of TADLIQ is 40 mg (10 mL) taken once daily with or without food. Please click link for full Prescribing Information: TAD-00030 SOURCE CMP Pharma