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 (mCRC).... Read More

BEHIND MVASI®

A ROBUST BIOSIMILARS PROGRAM

 
EXTRAPOLATION AND MVASI® MAPLE TRIAL DESIGN EFFICACY DATA SAFETY/ IMMUNOGENICITY DATA CLINICAL PK/ NONCLINICAL DATA

MVASI® DEMONSTRATED SIMILAR SAFETY AND IMMUNOGENICITY TO AVASTIN® 1

There were no new or unexpected side effects for MVASI® compared with Avastin®.1,2

INCIDENCE RATES FOR ADVERSE EVENTS OF INTEREST (EOI)2 GRADE ≥ 3
ADVERSE EVENTS OF INTEREST GRADE ≥ 3
MVASI®
(n = 324)
n (%)
AVASTIN®
(n = 309)
n (%)
Any EOI Grade ≥ 3
102 (31.5)
99 (32.0)
Neutropenia and infections
54 (16.7)
47 (15.2)
Infusion reactions
31 (9.6)
21 (6.8)
Hypertension
22 (6.8)
17 (5.5)
Thrombotic microangiopathy
13 (4.0)
20 (6.5)
Hemorrhages
11 (3.4)
6 (1.9)
Venous thromboembolic events
8 (2.5)
12 (3.9)
Peripheral sensory neuropathy
6 (1.9)
5 (1.6)
Arterial thromboembolic events
4 (1.2)
3 (1.0)
Gastrointestinal (GI) perforations
3 (0.9)
4 (1.3)
Hypersensitivity reactions
2 (0.6)
1 (0.3)
Pulmonary hemorrhage
2 (0.6)
5 (1.6)
Reversible posterior leukoen-cephalopathy syndrome-related
Reversible posterior leukoencephalopathy syndrome-related
2 (0.6)
2 (0.6)
Proteinuria
1 (0.3)
1 (0.3)
Congestive heart failure
1 (0.3)
1 (0.3)
Non-GI fistula formation
1 (0.3)
1 (0.3)
Surgery and wound healing complications
1 (0.3)
2 (0.6)

INCIDENCE OF BINDING ANTIBODIES WAS LOW AND SIMILAR TO AVASTIN® 1,2


THERE WERE NO NEUTRALIZING ANTIBODIES OBSERVED1,2

Important Safety Information

Serious adverse reactions (Warnings and Precautions)

  • Serious and sometimes fatal adverse reactions with increased incidence in the bevacizumab-treated arm vs chemotherapy arm included:
    • Gastrointestinal (GI) perforation ranged from 0.3% to 3% of patients across clinical studies
    • Non-GI fistulae (<1% to 1.8%, highest in patients with cervical cancer)
    • Arterial thromboembolic events (Grade ≥3, 5%, highest in patients with GBM)
    • The incidence of wound healing and surgical complications, including serious and fatal complications, is increased in MVASI®-treated patients
    • Hemorrhage (Grade 3–5) ranged from 0.4% to 7% of patients across clinical studies
    • Renal injury and proteinuria
      • Grade 3–4 proteinuria ranged from 0.7% to 7% in clinical studies
      • Nephrotic syndrome (<1%)
  • Additional serious adverse reactions 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): Grade ≥3 left ventricular dysfunction (1%)
    • Infusion-related reactions with the first dose of bevacizumab occurred in <3% of patients, and severe reactions occurred in 0.4% 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
  • 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 of MVASI®
  • Advise nursing women not to breastfeed during treatment with MVASI® and for 6 months following their last dose of treatment
  • MVASI® may impair fertility

Most common adverse reactions

  • Across studies, the most common adverse reactions observed in bevacizumab patients at a rate >10% were:
    • Epistaxis
    • Headache
    • Hypertension
    • Rhinitis
    • Proteinuria
    • Taste alteration
    • Dry skin
    • 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 reactions

  • 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 reactions 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, the incidence of Grade 3–4 VTE was 5% in patients receiving bevacizumab with chemotherapy compared to 2% in patients receiving chemotherapy alone. In this study, 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 reactions 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 reactions 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) reactions 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
  • When continued beyond first progression in MCRC, no new safety signals were observed in the TML study (ML18147) when bevacizumab was administered in second-line MCRC patients who progressed on a bevacizumab containing regimen in first-line MCRC. The safety data was consistent with the known safety profile established in first- and second-line MCRC

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.

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 (mCRC).

MVASI®, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy, is indicated for the second-line treatment of patients with mCRC 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 (NSCLC).

MVASI® is indicated for the treatment of recurrent glioblastoma (GBM) in adults.

MVASI®, in combination with interferon-alfa, is indicated for the treatment of metastatic renal cell carcinoma (mRCC).

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 (CC).

Avastin® (bevacizumab) is a registered trademark of Genentech USA, Inc.

MVASI® Important Safety Information

Serious adverse reactions (Warnings and Precautions)

  • Serious and sometimes fatal adverse reactions with increased incidence in the bevacizumab-treated arm vs chemotherapy arm included:
    • Gastrointestinal (GI) perforation ranged from 0.3% to 3% of patients across clinical studies

References: 1. Thatcher N, Goldschmidt JH, Thomas M, et al. Efficacy and safety of the biosimilar ABP 215 compared with bevacizumab in patients with advanced nonsquamous non-small cell lung cancer (MAPLE): a randomized, double-blind, phase III study. Clin Cancer Res. 2019;25:2088-2095. 2. Data on file, Amgen; 2015 [CSR 20120265].