Teva and Celltrion Announce the Availability of TRUXIMA (rituximab-abbs) Injection, the First Biosimilar to Rituxan (rituximab) in the United States -…

Posted: November 8, 2019 at 12:46 pm

JERUSALEM & PARSIPPANY, N.J. & INCHEON, South Korea--(BUSINESS WIRE)--Teva Pharmaceuticals USA, Inc., a U.S. affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA), Celltrion, Inc., (KRX KRX:068270) and Celltrion Healthcare, Co., Ltd. (KRX KOSDAQ:091990), today announced that TRUXIMA (rituximab-abbs) injection is the first biosimilar to the reference product Rituxan1 (rituximab) now available in the United States with a full oncology label. TRUXIMA is currently indicated for the treatment of adult patients with non-Hodgkins Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL):

We are excited about the first FDA-approved biosimilar to rituximab in the U.S., stated Brendan OGrady, Executive Vice President and Head of North America Commercial at Teva. Tevas commitment to biosimilars is focused on the potential to create lower healthcare costs and increased price competition. This focus is consistent with Tevas mission of making accessible medications to help improve the lives of patients.

TRUXIMA was approved by the U.S. Food and Drug Administration (FDA) as the first rituximab biosimilar. The approval was based on a review of a comprehensive data package inclusive of foundational and extensive analytical characterization, nonclinical data, clinical pharmacology, immunogenicity, clinical efficacy, and safety data. In May 2019, the FDA approved TRUXIMA to match all of the reference products oncology indications for NHL and CLL. In light of a patent settlement with Genentech, Celltrion and Teva have a pending FDA submission for rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA), and a license from Genentech to expand the TRUXIMA label to include these indications in Q2 2020.

We are pleased to announce the launch of the first rituximab biosimilar, TRUXIMA, with our marketing partner Teva in the U.S. said Mr. Hyoung-Ki Kim, Vice Chairman at Celltrion Healthcare. We believe that the introduction of TRUXIMA into the U.S. market will contribute to addressing unmet needs of U.S. patients as well.

The Wholesale Acquisition Cost (WAC or list price) for TRUXIMA will be 10 percent lower than the reference product. TRUXIMA is being made available through primary wholesalers at a WAC of $845.55 for 100mg vial and $4227.75 for 500mg vial. Actual costs to individual patients and providers for TRUXIMA are anticipated to be lower than WAC because WAC does not account for additional rebates and discounts that may apply. Savings on out-of-pocket costs may vary depending on the patients insurance payer and eligibility for participation in the assistance program.

Dedicated patient support services are also available from Teva through the Comprehensive Oncology Reimbursement Expertise (CORE) program. CORE is available to help eligible patients, caregivers and healthcare professionals navigate the reimbursement process. CORE offers a range of services, including benefits verification and coverage determination, support for precertification and prior authorization, assistance with coverage guidelines and claims investigation, and support through the claims and appeals process. A savings program is also available for eligible commercially insured patients. To learn more, please visit TevaCORE.com. For healthcare professionals seeking additional information, there is also a dedicated site at TRUXIMAhcp.com.

Celltrion and Teva Pharmaceutical Industries Ltd. entered into an exclusive partnership in October 2016 to commercialize TRUXIMA in the U.S. and Canada.

Please see the Important Safety Information below including the Boxed Warning regarding fatal infusion-related reactions, severe mucocutaneous reactions, hepatitis B virus reactivation and progressive multifocal leukoencephalopathy. For more information, please visit the full prescribing information.

Important Safety Information

WARNING: FATAL INFUSION-RELATED REACTIONS, SEVERE MUCOCUTANEOUS REACTIONS, HEPATITIS B VIRUS REACTIVATION and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY

Infusion-Related Reactions - Administration of rituximab products, including TRUXIMA, can result in serious, including fatal, infusion-related reactions. Deaths within 24 hours of rituximab infusion have occurred. Approximately 80% of fatal infusion-related reactions occurred in association with the first infusion. Monitor patients closely. Discontinue TRUXIMA infusion for severe reactions and provide medical treatment for Grade 3 or 4 infusion-related reactions

Severe Mucocutaneous Reactions - Severe, including fatal, mucocutaneous reactions can occur in patients receiving rituximab products

Hepatitis B Virus (HBV) Reactivation - HBV reactivation can occur in patients treated with rituximab products, in some cases resulting in fulminant hepatitis, hepatic failure, and death. Screen all patients for HBV infection before treatment initiation, and monitor patients during and after treatment with TRUXIMA. Discontinue TRUXIMA and concomitant medications in the event of HBV reactivation

Progressive Multifocal Leukoencephalopathy (PML), including fatal PML, can occur in patients receiving rituximab products

Warnings and Precautions

Infusion-Related Reactions - Rituximab products can cause severe, including fatal, infusion-related reactions. Severe reactions typically occurred during the first infusion with time to onset of 30-120 minutes. Rituximab product-induced infusion-related reactions and sequelae include urticaria, hypotension, angioedema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, anaphylactoid events, or death.

Premedicate patients with an antihistamine and acetaminophen prior to dosing. Institute medical management (e.g. glucocorticoids, epinephrine, bronchodilators, or oxygen) for infusion-related reactions as needed. Depending on the severity of the infusion-related reaction and the required interventions, temporarily or permanently discontinue TRUXIMA. Resume infusion at a minimum 50% reduction in rate after symptoms have resolved. Closely monitor the following patients: those with pre-existing cardiac or pulmonary conditions, those who experienced prior cardiopulmonary adverse reactions, and those with high numbers of circulating malignant cells (>25,000/mm3)

Severe Mucocutaneous Reactions - Mucocutaneous reactions, some with fatal outcome, can occur in patients treated with rituximab products. These reactions include paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis. The onset of these reactions has been variable and includes reports with onset on the first day of rituximab exposure. Discontinue TRUXIMA in patients who experience a severe mucocutaneous reaction. The safety of re-administration of rituximab products to patients with severe mucocutaneous reactions has not been determined.

Hepatitis B Virus Reactivation - Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients treated with drugs classified as CD20-directed cytolytic antibodies, including rituximab products. Cases have been reported in patients who are hepatitis B surface antigen (HBsAg) positive and also in patients who are HBsAg negative but are hepatitis B core antibody (anti-HBc) positive. Reactivation also has occurred in patients who appear to have resolved hepatitis B infection (i.e., HBsAg negative, anti-HBc positive and hepatitis B surface antibody [anti-HBs] positive).

HBV reactivation is defined as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA levels or detection of HBsAg in a person who was previously HBsAg negative and anti-HBc positive. Reactivation of HBV replication is often followed by hepatitis, i.e., increase in transaminase levels. In severe cases increase in bilirubin levels, liver failure, and death can occur.

Screen all patients for HBV infection by measuring HBsAg and anti-HBc before initiating treatment with TRUXIMA. For patients who show evidence of prior hepatitis B infection (HBsAg positive [regardless of antibody status] or HBsAg negative but anti-HBc positive), consult with physicians with expertise in managing hepatitis B regarding monitoring and consideration for HBV antiviral therapy before and/or during TRUXIMA treatment.

Monitor patients with evidence of current or prior HBV infection for clinical and laboratory signs of hepatitis or HBV reactivation during and for several months following TRUXIMA therapy. HBV reactivation has been reported up to 24 months following completion of rituximab therapy.

In patients who develop reactivation of HBV while on TRUXIMA, immediately discontinue TRUXIMA and any concomitant chemotherapy, and institute appropriate treatment. Insufficient data exist regarding the safety of resuming TRUXIMA treatment in patients who develop HBV reactivation. Resumption of TRUXIMA treatment in patients whose HBV reactivation resolves should be discussed with physicians with expertise in managing HBV.

Progressive Multifocal Leukoencephalopathy (PML) - JC virus infection resulting in PML and death can occur in rituximab product-treated patients with hematologic malignancies. The majority of patients with hematologic malignancies diagnosed with PML received rituximab in combination with chemotherapy or as part of a hematopoietic stem cell transplant. Most cases of PML were diagnosed within 12 months of their last infusion of rituximab.

Consider the diagnosis of PML in any patient presenting with new-onset neurologic manifestations. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture.

Discontinue TRUXIMA and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML.

Tumor Lysis Syndrome (TLS) - Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia from tumor lysis, sometimes fatal, can occur within 12-24 hours after the first infusion of rituximab products in patients with NHL. A high number of circulating malignant cells (>25,000/mm3) or high tumor burden, confers a greater risk of TLS.

Administer aggressive intravenous hydration and anti-hyperuricemic therapy in patients at high risk for TLS. Correct electrolyte abnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis as indicated.

Infections - Serious, including fatal, bacterial, fungal, and new or reactivated viral infections can occur during and following the completion of rituximab product-based therapy. Infections have been reported in some patients with prolonged hypogammaglobulinemia (defined as hypogammaglobulinemia >11 months after rituximab exposure). New or reactivated viral infections included cytomegalovirus, herpes simplex virus, parvovirus B19, varicella zoster virus, West Nile virus, and hepatitis B and C. Discontinue TRUXIMA for serious infections and institute appropriate anti-infective therapy. TRUXIMA is not recommended for use in patients with severe, active infections.

Cardiovascular Adverse Reactions - Cardiac adverse reactions, including ventricular fibrillation, myocardial infarction, and cardiogenic shock may occur in patients receiving rituximab products. Discontinue infusions for serious or life-threatening cardiac arrhythmias. Perform cardiac monitoring during and after all infusions of TRUXIMA for patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina.

Renal Toxicity - Severe, including fatal, renal toxicity can occur after rituximab product administration in patients with NHL. Renal toxicity has occurred in patients who experience tumor lysis syndrome and in patients with NHL administered concomitant cisplatin therapy during clinical trials. The combination of cisplatin and TRUXIMA is not an approved treatment regimen. Monitor closely for signs of renal failure and discontinue TRUXIMA in patients with a rising serum creatinine or oliguria.

Bowel Obstruction and Perforation - Abdominal pain, bowel obstruction and perforation, in some cases leading to death, can occur in patients receiving rituximab in combination with chemotherapy. In postmarketing reports, the mean time to documented gastrointestinal perforation was 6 (range 1-77) days in patients with NHL. Evaluate if symptoms of obstruction such as abdominal pain or repeated vomiting occur.

Immunization - The safety of immunization with live viral vaccines following rituximab product therapy has not been studied and vaccination with live virus vaccines is not recommended before or during treatment.

Embryo-Fetal Toxicity - Based on human data, rituximab products can cause fetal harm due to B-cell lymphocytopenia in infants exposed to rituximab in-utero. Advise pregnant women of the risk to a fetus. Females of childbearing potential should use effective contraception while receiving TRUXIMA and for 12 months following the last dose of TRUXIMA.

Most common adverse reactions in clinical trials of NHL (>25%) were: infusion-related reactions, fever, lymphopenia, chills, infection, and asthenia

Most common adverse reactions in clinical trials of CLL (>25%) were: infusion-related reactions and neutropenia

Nursing Mothers - There are no data on the presence of rituximab in human milk, the effect on the breastfed child, or the effect on milk production. Since many drugs including antibodies are present in human milk, advise a lactating woman not to breastfeed during treatment and for at least 6 months after the last dose of TRUXIMA due to the potential for serious adverse reactions in breastfed infants.

About TRUXIMA

TRUXIMA (rituximab-abbs) is a U.S. Food and Drug Administration (FDA)-approved biosimilar to RITUXAN (rituximab) for the treatment of adult patients with CD20-positive, B-cell NHL to be used as a single agent or in combination with chemotherapy or CLL in combination with fludarabine and cyclophosphamide (FC).

TRUXIMA has the same mechanism of action as Rituxan and has demonstrated biosimilarity to Rituxan through a totality of evidence.

About Celltrion Healthcare, Co. Ltd.

Celltrion Healthcare conducts the worldwide marketing, sales and distribution of biological medicines developed by Celltrion, Inc. through an extensive global network that spans more than 120 different countries. Celltrion Healthcares products are manufactured at state-of-the-art mammalian cell culture facilities, designed and built to comply with the US Food and Drug Administration (FDA) cGMP guidelines and the EU GMP guidelines.

About Celltrion, Inc.

Headquartered in Incheon, Korea, Celltrion is a leading biopharmaceutical company, specializing in research, development and manufacturing of biosimilar and innovative drugs. Celltrion strives to provide more affordable biosimilar mAbs to patients who previously had limited access to advanced therapeutics. Celltrion received FDA approval for TRUXIMA (rituximab-abbs) and HERZUMA (trastuzumab-pkrb) in 2018.

About Teva

Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) has been developing and producing medicines to improve peoples lives for more than a century. We are a global leader in generic and specialty medicines with a portfolio consisting of over 3,500 products in nearly every therapeutic area. Around 200 million people around the world take a Teva medicine every day, and are served by one of the largest and most complex supply chains in the pharmaceutical industry. Along with our established presence in generics, we have significant innovative research and operations supporting our growing portfolio of specialty and biopharmaceutical products. Learn more at http://www.tevapharm.com.

Teva's Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 regarding TRUXIMA, which are based on managements current beliefs and expectations and are subject to substantial risks and uncertainties, both known and unknown, that could cause our future results, performance or achievements to differ significantly from that expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include risks relating to:

and other factors discussed in our Quarterly Reports on Form 10-Q for the first and second quarter of 2019 and in our Annual Report on Form 10-K for the year ended December 31, 2018, including in the sections captioned "Risk Factors and Forward Looking Statements. Forward-looking statements speak only as of the date on which they are made, and we assume no obligation to update or revise any forward-looking statements or other information contained herein, whether as a result of new information, future events or otherwise. You are cautioned not to put undue reliance on these forward-looking statements.

1 RITUXAN is a registered trademark of Genentech and Biogen.

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Teva and Celltrion Announce the Availability of TRUXIMA (rituximab-abbs) Injection, the First Biosimilar to Rituxan (rituximab) in the United States -...

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