FLASCO

FDA Approves Amgen And Allergan’s KANJINTI™ (trastuzumab-anns),

  • FLASCO
  • June 19, 2019

Amgen (NASDAQ:AMGN) and Allergan plc (NYSE:AGN) announced that the U.S. Food and Drug Administration (FDA) has approved KANJINTI™ (trastuzumab-anns) for all approved indications of the reference product, Herceptin® (trastuzumab):  for the treatment of HER2-overexpressing adjuvant and metastatic breast cancer and HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma.

“The FDA approval of KANJINTI is an important milestone for our biosimilars portfolio, providing an additional treatment option for patients across three types of cancer,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen. “KANJINTI is the third biosimilar from our portfolio to receive FDA approval, highlighting our long-term commitment to providing patients with serious illnesses access to high-quality biological therapies.”

KANJINTI was proven to be highly similar to, and to have no clinically meaningful differences from, Herceptin based on a comprehensive totality of evidence which included extensive comparative analytical, pharmacokinetic and clinical data. At the time of approval, KANJINTI is the only trastuzumab biosimilar to incorporate the evaluation of a single transition in the clinical study, demonstrating similar safety and immunogenicity in patients who were previously on Herceptin.

“KANJINTI is the second of four biosimilars from Amgen and Allergan’s collaboration to be approved by the FDA,” said David Nicholson, chief research and development officer at Allergan. “We are proud of the progress being made as we continuously strive to develop and deliver high-quality cancer therapies in collaboration with Amgen.”

Amgen has a total of 10 biosimilars in its portfolio, three of which have been approved in the U.S. and three that are approved in the European Union (EU).

About KANJINTI™ (trastuzumab-anns) in the U.S.
KANJINTI is a biosimilar to trastuzumab, a recombinant DNA-derived humanized monoclonal immunoglobulin G1 kappa antibody. The active ingredient of KANJINTI is a humanized monoclonal antibody that has the same amino acid sequence, structure and function as trastuzumab. KANJINTI has the same pharmaceutical dosage form and same strength after reconstitution as trastuzumab.

KANJINTI is currently not available commercially.  This is not an offer for sale. The following information is derived from the approved label in the U.S.

In the U.S., KANJINTI is approved for:

Adjuvant Breast Cancer
KANJINTI is indicated for 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 containing doxorubicin, cyclophosphamide and either paclitaxel or docetaxel
  • With docetaxel and carboplatin
  • As a single agent following multi-modality anthracycline-based therapy

Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product.

* High-risk is defined as ER/PR positive with one of the following features: tumor size >2 cm, age <35 years, or tumor grade 2 or 3.

Metastatic Breast Cancer
KANJINTI is indicated:

  • In combination with paclitaxel for the 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

Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product.

Metastatic Gastric Cancer
KANJINTI 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.

Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product.

KANJINTI U.S. Boxed WARNINGS and Important Safety Information

Boxed WARNINGS and Additional Important Safety Information
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 KANJINTI™. Discontinue KANJINTI™ treatment in patients receiving adjuvant therapy and withhold KANJINTI™ 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 KANJINTI™ infusion for dyspnea or clinically significant hypotension. Monitor patients until symptoms completely resolve. Discontinue KANJINTI™ 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

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. In a pivotal adjuvant breast cancer trial, one patient who developed CHF died of cardiomyopathy
  • Trastuzumab can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death
  • Trastuzumab can also cause asymptomatic decline in LVEF
  • Discontinue KANJINTI™ treatment in patients receiving adjuvant breast cancer therapy and withhold KANJINTI™ in patients with metastatic disease for clinically significant decrease in left ventricular function

Cardiac Monitoring

  • Evaluate cardiac function prior to and during treatment. For adjuvant breast cancer therapy, also evaluate cardiac function after completion of KANJINTI™
  • 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 KANJINTI™ treatment
  • Monitor more frequently if KANJINTI™ is withheld for significant left ventricular cardiac dysfunction

Infusion Reactions

  • KANJINTI™ administration can result in serious and fatal infusion reactions
  • Symptoms usually occur during or within 24 hours of KANJINTI™ administration
  • Interrupt KANJINTI™ infusion for dyspnea or clinically significant hypotension
  • Monitor patients until symptoms completely resolve
  • Discontinue KANJINTI™ for infusion reactions manifesting as anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. 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 include 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 KANJINTI™
  • Advise pregnant women and females of reproductive potential that exposure to KANJINTI™ 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 at least 7 months following the last dose of KANJINTI™. 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 KANJINTI™treatment and any potential adverse effects on the breastfed child from KANJINTI™ or from the underlying maternal condition

Pulmonary Toxicity

  • Trastuzumab products can result in serious and fatal pulmonary toxicity, which includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, noncardiogenic 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 KANJINTI™ in patients experiencing pulmonary toxicity

Exacerbation of Chemotherapy-Induced Neutropenia

  • In randomized, controlled clinical trials, the per-patient incidences of NCI-CTC Grade 3-4 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

  • The most common adverse reactions associated with trastuzumab products in breast cancer were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia
  • The most common adverse reactions associated with trastuzumab products in metastatic gastric cancer were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia

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