On March 16, 2020 Teva Pharmaceuticals USA, Inc., a U.S. affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA), and Celltrion Healthcare, Co., Ltd. (KRX KOSDAQ:091990), reported that HERZUMA1 (trastuzumab-pkrb) for Injection, a biosimilar to HERCEPTIN1, is now available in the United States with the same indications as the reference product including (Press release, Teva, MAR 16, 2020, View Source [SID1234555615]):

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Adjuvant Breast Cancer
HERZUMA is indicated for the adjuvant treatment of HER2-overexpressing node-positive or node-negative (ER/PR negative or with one high-risk feature) breast cancer
as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel
as part of a treatment regimen with docetaxel and carboplatin
as a single agent following multi-modality anthracycline based therapy
Metastatic Breast Cancer
HERZUMA is indicated:
In combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer
As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease
Metastatic Gastric Cancer
HERZUMA is indicated in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease.
In these indications, patients should be selected for therapy based on a U.S. Food and Drug Administration (FDA)-approved companion diagnostic for a trastuzumab product.

"We are proud to make HERZUMA available to patients in the U.S. living with HER2-positive breast and gastric cancers, and their providers," said Brendan O’Grady, Executive Vice President, North America Commercial, Teva. "The launch of HERZUMA continues our commitment to help lower healthcare costs and increase price competition through the availability of biosimilars. Teva is continuing to invest in biopharmaceuticals as part of our long-term strategy for the future, and to help patients around the world, and we look forward to additional milestones for our biosimilar products later this year."

HERZUMA has received FDA approval for the same indications of the reference product.

"We are pleased that HERZUMA is now available to patients in the U.S.," said Mr. Hyoung-Ki Kim, Vice Chairman at Celltrion Healthcare. "We look forward to continuing our partnership with Teva to bring biosimilars to as many patients as possible in the U.S., as we believe they address an unmet need in the market."

The Wholesale Acquisition Cost (WAC or "list price") for HERZUMA 150 mg is $1,402.50 and HERZUMA 420 mg is $3,927, which is a 10 percent discount to the WAC of HERCEPTIN. Actual costs to individual patients and providers for HERZUMA 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 patient’s insurance payer and eligibility for participation in the assistance program.

Dedicated patient support services are also available from Teva through the 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.

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

Trastuzumab products have a Boxed Warning, which states that treatment with trastuzumab may be associated with cardiomyopathy, infusion reactions, pulmonary toxicity and embryo-fetal toxicity. Please see the full Boxed Warning and additional Important Safety Information in this release and accompanying Prescribing Information.

Important Safety Information

WARNING: CARDIOMYOPATHY, INFUSION REACTIONS, EMBRYO‑FETAL TOXICITY, AND PULMONARY TOXICITY

Cardiomyopathy – Administration of trastuzumab products can result in sub-clinical and clinical cardiac failure. The incidence and severity was highest in patients receiving trastuzumab with anthracycline‑containing chemotherapy regimens.

Evaluate left ventricular function in all patients prior to and during treatment with HERZUMA. Discontinue HERZUMA treatment in patients receiving adjuvant therapy and withhold HERZUMA in patients with metastatic disease for clinically significant decrease in left ventricular function.

Infusion Reactions; Pulmonary Toxicity – Administration of trastuzumab products can result in serious and fatal infusion reactions and pulmonary toxicity. Symptoms usually occur during or within 24 hours of administration. Interrupt HERZUMA infusion for dyspnea or clinically significant hypotension. Monitor patients until symptoms completely resolve. Discontinue HERZUMA for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome.

Embryo-Fetal Toxicity – Exposure to trastuzumab products during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise patients of these risks and the need for effective contraception.

WARNINGS AND PRECAUTIONS

Cardiomyopathy

Administration of trastuzumab products can result in sub-clinical and clinical cardiac failure. The incidence and severity was highest in patients receiving trastuzumab with anthracycline‑containing chemotherapy regimens
Trastuzumab products can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death
Trastuzumab products can also cause asymptomatic decline in left ventricular ejection fraction (LVEF)
Discontinue HERZUMA treatment in patients receiving adjuvant therapy and withhold HERZUMA in patients with metastatic disease for clinically significant decrease in left ventricular function
The safety of continuation or resumption of HERZUMA in patients with trastuzumab product-induced LV cardiac dysfunction has not been studied
Cardiac Monitoring

Evaluate cardiac function prior to and during treatment. For adjuvant breast cancer therapy, also evaluate cardiac function after completion of HERZUMA
Conduct thorough cardiac assessment, including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan
Monitor frequently for decreased left ventricular function during and after HERZUMA treatment
Monitor more frequently if HERZUMA is withheld for significant left ventricular cardiac dysfunction
Infusion Reactions

Administration of trastuzumab products can result in serious and fatal infusion reactions
Symptoms usually occur during or within 24 hours of administration
Interrupt HERZUMA infusion for dyspnea or clinically significant hypotension
Monitor patients until symptoms completely resolve
Discontinue HERZUMA for anaphylaxis or angioedema. Strongly consider permanent discontinuation in all patients with severe infusion reactions
Infusion reactions consist of a symptom complex characterized by fever and chills, and on occasion included nausea, vomiting, pain (in some cases at tumor sites), headache, dizziness, dyspnea, hypotension, rash, and asthenia
Embryo-Fetal Toxicity

Exposure to trastuzumab products during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise patients of these risks and the need for effective contraception
Verify the pregnancy status of females of reproductive potential prior to the initiation of HERZUMA
Advise pregnant women and females of reproductive potential that exposure to HERZUMA during pregnancy or within 7 months prior to conception can result in fetal harm
Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of HERZUMA. Advise female patients to contact their healthcare provider with a known or suspected pregnancy
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for HERZUMA treatment and any potential adverse effects on the breastfed child from HERZUMA or from the underlying maternal condition
Pulmonary Toxicity

Administration of trastuzumab products can result in serious and fatal pulmonary toxicity, which includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, non‑cardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Such events can occur as sequelae of infusion reactions
Patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest, appear to have more severe toxicity
Discontinue HERZUMA in patients experiencing pulmonary toxicity
Exacerbation of Chemotherapy-Induced Neutropenia

In randomized, controlled clinical trials, the per-patient incidences of NCI-CTC Grade 3 to 4 neutropenia and of febrile neutropenia were higher in patients receiving trastuzumab in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone. The incidence of septic death was similar among patients who received trastuzumab and those who did not
Most Common Adverse Reactions

Adjuvant Breast Cancer – Most common adverse reactions (≥5%) are headache, diarrhea, nausea, and chills
Metastatic Breast Cancer- Most common adverse reactions (≥10%) are fever, chills, headache, infection, congestive heart failure, insomnia, cough, and rash
Metastatic Gastric Cancer- Most common adverse reactions (≥10%) are neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia
Please click here for full Prescribing Information for HERZUMA, including BOXED WARNINGS.

About HERZUMA

HERZUMA (trastuzumab-pkrb) for Injection is a U.S. FDA-approved biosimilar to Herceptin with no clinically meaningful differences in safety, purity and potency. HERZUMA is used in adults to treat HER2+ breast cancer and metastatic gastric cancer. HERZUMA has the same mechanism of action as Herceptin and has demonstrated biosimilarity to Herceptin 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 Healthcare’s products are manufactured at state-of-the-art mammalian cell culture facilities, designed and built to comply with the US FDA cGMP guidelines and the EU GMP guidelines.