MVASI™ Indications

MVASI™ is a vascular endothelial growth factor inhibitor indicated for the treatment of: MVASI™, in combination with intravenous fluorouracil-based chemotherapy, is indicated for the first- or second-line treatment of patients with metastatic colorectal cancer... Read More

BEHIND MVASI™

ANSWERING THE GROWINGNEED FOR BIOSIMILARS

 

At Amgen, we're committed to the development of biosimilars because of the additional treatment options they provide to patients and the positive impact they can have on the entire health care system.

HERITAGE

WITH MVASI™, AMGEN CONTINUES TO BE DEDICATED TO ONCOLOGY TREATMENT AND CARE

Amgen Biologics – 40 years of experience

For four decades, Amgen has been at the forefront of biologic innovation with the discovery, development, and production of novel medicines and support services for patients with cancer.

Amgen Biosimilars heritage

HERITAGE
To learn more about Amgen’s heritage in biologics and biosimilars, visit AmgenBiosimilars.com.

EXPERTISE

MANUFACTURING QUALITY BIOSIMILARS, LIKE MVASI™, TAKES EXPERIENCE AND EXPERTISE

300 quality checks during manufacturing
  • Amgen Biosimilars are developed to the same high standards as our innovative biologics.
  • Our rigorous processes are designed to ensure batch-to-batch consistency, quality, safety, and compliance with FDA regulatory requirements.

A RIGOROUS APPROACH TO ESTABLISHING BIOSIMILARITY2,3

The FDA requires a totality of evidence* to establish similarity.2

  • Establishing molecular similarity is the foundation of demonstrating biosimilar totality of evidence.2
  • The goal of biosimilar trials is to confirm no clinically meaningful differences between the biosimilar and reference drug.2,3

ORIGINATOR DRUG DEVELOPMENT

Goal is to establish efficacy and safety of the medication2,3

BIOSIMILAR DRUG DEVELOPMENT

Goal is to prove similarity to the originator drug across different characteristics2,3

Biosimilar drug development Biosimilar drug development

CLINICAL STUDIES: Demonstrate no clinically meaningful differences in safety and efficacy.

CLINICAL PHARMACOLOGY: Confirm bioequivalence.

NONCLINICAL STUDIES: Demonstrate similar activity, potency, and toxicity.

ANALYTICAL COMPARISON: Establish structural and functional similarity.

For more educational information on biosimilars, visit BioEngage.

*Totality of evidence establishes structural and functional equivalence, and includes nonclinical evaluation, human pharmacokinetic (PK) and pharmacodynamic (PD) data, clinical immunogenicity data, and comparative clinical study data.2


SETTING A HIGH STANDARD FOR BIOSIMILAR MANUFACTURING

  • Manufacturing biosimilars, like MVASI™, is a complex process that requires custom cell lines, new manufacturing processes—and considerable expertise.2,3
  • Amgen is well positioned to address these complexities by setting rigorous quality standards for all of our products.
Biosimilar manufacturing to ensure similarity

BIOSIMILARS ARE COMPLEX4

Difference between generics and biosimilars Difference between generics and biosimilars

Da = Dalton, 1 atomic mass unit; mAb = monoclonal antibody.

For more educational information on biosimilars, visit BioEngage.

EXPERTISE
To learn more about Amgen’s expertise in biologics and biosimilars, visit AmgenBiosimilars.com.

BioEngage

To learn more about biosimilars, visit AmgenBiosimilars.com/BioEngage.

COMMITMENT

AMGEN HAS AN UNWAVERING COMMITMENT TO DELIVER OUR PRODUCTS, INCLUDING MVASI™, TO EVERY PATIENT, EVERY TIME

In the last decade, Amgen has achieved zero supply shortages
  • Our strong manufacturing and distribution network helps ensure patients can get the medicines they need.
  • Every manufacturing facility strictly adheres to the same processes and quality-control measures.
  • We invest heavily in risk mitigation on all levels to ensure supply and safety.
Amgen Biosimilars Commitment

COMMITMENT
To learn more about Amgen’s commitment to serve patients, visit AmgenBiosimilars.com.

SUPPORT

With both Amgen Assist 360™ and Amgen FIRST STEP™ programs available for our biosimilars, you’ll see the same support you’ve come to expect from Amgen.

MVASI™ Important Safety Information

  • Gastrointestinal (GI) perforation
    • Serious and sometimes fatal GI perforation occurred at a higher incidence in bevacizumab-treated patients compared to patients treated with chemotherapy
    • The incidence of GI perforation ranged from 0.3% to 3% across clinical studies
    • Discontinue MVASI™ in patients with GI perforation
  • Surgery and Wound Healing Complications
    • The incidence of wound healing and surgical complications, including serious and fatal complications, is increased in bevacizumab-treated patients
    • Withhold MVASI™ for at least 28 days prior to elective surgery. Do not administer MVASI™ for at least 28 days after surgery and until the wound is fully healed
    • Discontinue in patients with wound healing complications requiring medical intervention
  • Hemorrhage
    • Severe or fatal hemorrhage, including hemoptysis, GI bleeding, hematemesis, central nervous system hemorrhage, epistaxis, and vaginal bleeding, occurred up to 5-fold more frequently in patients receiving bevacizumab. In clinical studies, the incidence of grade ≥3 hemorrhagic events among patients receiving bevacizumab ranged from 0.4% to 7%
    • Do not administer MVASI™ to patients with serious hemorrhage or a recent history of hemoptysis (≥1/2 tsp of red blood)
    • Discontinue MVASI™ in patients who develop grade 3–4 hemorrhage
  • Additional serious and sometimes fatal adverse events with increased incidence in the bevacizumab-treated arm vs chemotherapy arm included:
    • Non-GI fistulae (<1% to 1.8%, highest in patients with cervical cancer)
    • Arterial thromboembolic events (grade ≥3, 5%, highest in patients with GBM)
    • Renal injury and proteinuria
      • Grade 3–4 proteinuria ranged from 0.7% to 7% in clinical studies
      • Nephrotic syndrome (<1%)
  • Additional serious adverse events with increased incidence in the bevacizumab-treated arm vs chemotherapy arm included:
    • Venous thromboembolism (grade ≥3, 11% seen in GOG-0240)
    • Hypertension (grade 3–4, 5%–18%)
    • Posterior reversible encephalopathy syndrome (PRES) (<0.5%)
    • Congestive heart failure (CHF) (1%)
  • Infusion reactions with the first dose of bevacizumab occurred in <3% of patients, and severe reactions occurred in 0.2% of patients
  • Avoid use in patients with ovarian cancer who have evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction
  • Inform females of reproductive potential of the risk of ovarian failure prior to initiating treatment with MVASI™

Pregnancy warning

  • Based on the mechanism of action and animal studies, MVASI™ may cause fetal harm when administered to pregnant women
  • Advise female patients that MVASI™ may cause fetal harm, and to inform their healthcare provider of a known or suspected pregnancy
  • Advise females of reproductive potential to use effective contraception during treatment with MVASI™ and for 6 months after the last dose
  • Advise nursing women that breastfeeding is not recommended during treatment with MVASI™ and for 6 months following their last dose of treatment
  • MVASI™ may impair fertility

Most common adverse events

  • Across studies, the most common adverse reactions observed in bevacizumab-treated patients at a rate >10% were:
    • Epistaxis
    • Headache
    • Hypertension
    • Rhinitis
    • Proteinuria
    • Taste alteration
    • Dry skin
    • Rectal hemorrhage
    • Lacrimation disorder
    • Back pain
    • Exfoliative dermatitis
  • Across all studies, bevacizumab was discontinued in 8% to 22% of patients because of adverse reactions

Indication-specific adverse events

  • In CC, grade 3 or 4 adverse reactions in Study GOG-0240, occurring at a higher incidence (≥2%) in 218 patients receiving bevacizumab plus chemotherapy compared to 222 patients receiving chemotherapy alone, were abdominal pain (12% vs 10%), diarrhea (6% vs 3%), anal fistula (4% vs 0%), proctalgia (3% vs 0%), urinary tract infection (8% vs 6%), cellulitis (3% vs 0.5%), fatigue (14% vs 10%), hypertension (11% vs 0.5%), thrombosis (8% vs 3%), hypokalemia (7% vs 4%), hyponatremia (4% vs 1%), dehydration (4% vs 0.5%), neutropenia (8% vs 4%), lymphopenia (6% vs 3%), back pain (6% vs 3%), and pelvic pain (6% vs 1%)
  • In mRCC, the most common grade 3–5 adverse events in AVOREN, occurring at a >2% higher incidence in bevacizumab-treated patients vs controls, were fatigue (13% vs 8%), asthenia (10% vs 7%), proteinuria (7% vs 0%), hypertension (6% vs 1%, including hypertension and hypertensive crisis), and hemorrhage (3% vs 0.3%;, including epistaxis, small intestinal hemorrhage, aneurysm ruptured, gastric ulcer hemorrhage, gingival bleeding, hemoptysis, hemorrhage intracranial, large intestinal hemorrhage, respiratory tract hemorrhage, and traumatic hematoma)
  • In rGBM Study EORTC 26101, 22% of patients discontinued treatment in the bevacizumab with lomustine arm due to adverse reactions compared with 10% of patients in the lomustine arm. In patients receiving bevacizumab with lomustine, the adverse reaction profile was similar to that observed in other approved indications
  • In NSCLC, grade 3–5 (nonhematologic) and grade 4–5 (hematologic) adverse events in Study E4599 occurring at a ≥2% higher incidence in bevacizumab-treated patients vs controls were neutropenia (27% vs 17%), fatigue (16% vs 13%), hypertension (8% vs 0.7%), infection without neutropenia (7% vs 3%), venous thromboembolism (5% vs 3%), febrile neutropenia (5% vs 2%), pneumonitis/pulmonary infiltrates (5% vs 3%), infection with grade 3 or 4 neutropenia (4% vs 2%), hyponatremia (4% vs 1%), headache (3% vs 1%), and proteinuria (3% vs 0%)
  • In first-line mCRC, the most common grade 3–4 events in Study 2107, which occurred at a ≥2% higher incidence in the bevacizumab plus IFL vs IFL groups, were asthenia (10% vs 7%), abdominal pain (8% vs 5%), pain (8% vs 5%), hypertension (12% vs 2%), deep vein thrombosis (9% vs 5%), intra-abdominal thrombosis (3% vs 1%), syncope (3% vs 1%), diarrhea (34% vs 25%), constipation (4% vs 2%), leukopenia (37% vs 31%), and neutropenia (21% vs 14%)
  • In second-line mCRC, the most common grade 3–5 (nonhematologic) and 4–5 (hematologic) events in Study E3200, which occurred at a higher incidence (≥2%) in the bevacizumab plus FOLFOX4 vs FOLFOX4 groups, were fatigue (19% vs 13%), diarrhea (18% vs 13%), sensory neuropathy (17% vs 9%), nausea (12% vs 5%), vomiting (11% vs 4%), dehydration (10% vs 5%), hypertension (9% vs 2%), abdominal pain (8% vs 5%), hemorrhage (5% vs 1%), other neurological (5% vs 3%), ileus (4% vs 1%), and headache (3% vs 0%). These data are likely to underestimate the true adverse event rates due to the reporting mechanisms used in this study

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Amgen at 1-800-772-6436.

Please see full Prescribing Information for additional Important Safety Information.

MVASI™ Indications

MVASI™ is a vascular endothelial growth factor inhibitor indicated for the treatment of:

MVASI™, in combination with intravenous fluorouracil-based chemotherapy, is indicated for the first- or second-line treatment of patients with metastatic colorectal cancer.

MVASI™, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy, is indicated for the second-line treatment of patients with metastatic colorectal cancer who have progressed on a first-line bevacizumab product-containing regimen.

Limitations of Use: MVASI™ is not indicated for adjuvant treatment of colon cancer.

MVASI™, in combination with carboplatin and paclitaxel, is indicated for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer.

MVASI™ is indicated for the treatment of recurrent glioblastoma in adults.

MVASI™, in combination with interferon-alfa, is indicated for the treatment of metastatic renal cell carcinoma.

MVASI™, in combination with paclitaxel and cisplatin or paclitaxel and topotecan, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer.

MVASI™ Important Safety Information

  • Gastrointestinal (GI) perforation
    • Serious and sometimes fatal GI perforation occurred at a higher incidence in bevacizumab-treated patients compared to patients treated with chemotherapy
    • The incidence of GI perforation ranged from 0.3% to 3% across clinical studies

 

References: 1. Data on file, Amgen; 2019 [Biologics Quality Checks]. 2. US Food and Drug Administration. Scientific considerations in demonstrating biosimilarity to a reference product. www.fda.gov/downloads/drugs/guidances/ucm291128.pdf. Accessed June 8, 2019. 3. US Food and Drug Administration. ODAC briefing document: ABP 215, a proposed biosimilar to US-Avastin. BLA 761028. July 13, 2017. 4. Camacho LH, Frost CP, Abella E, Morrow PK, Whittaker S. Biosimilars 101: considerations for U.S. oncologists in clinical practice. Cancer Med. 2014;3:889-899. 5. Aspirin Prescribing Information, Bayer. 6. Humalog® (insulin lispro injection) Prescribing Information [revised 2017], Eli Lilly. 7. Humatrope® [somatropin (rDNA ORIGIN)] Prescribing Information [revised 2016], Eli Lilly. 8. Taltz® (ixekizumab) Prescribing Information [revised 2017], Eli Lilly. 9. Nickish K, Bode-Greuel KM. NPV modelling for the selection of value-creating biosimilar development candidates. J Commer Biotechnol. 2013;19:24-32. 10. Data on file, Amgen; 2018. 11. Data on file, Amgen; 2019.