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™

A ROBUST BIOSIMILARS PROGRAM

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

MVASI™ MEETS ALL FDA REQUIREMENTS FOR BIOSIMILARITY1,2

MVASI™ is highly similar to Avastin® based on a totality of evidence, with no clinically meaningful differences in safety of efficacy.1,3

REQUIREMENTS FOR BIOSIMILAR APPROVAL3,4
MVASI™ 1,5-8
Analytical comparison
In vitro analytical studies
Nonclinical studies
Colon cancer xenograft mouse models
Clinical pharmacology
Clinical PK studies
Comparative clinical study
MAPLE study
Sensitive patient population
NSCLC patients*

The MAPLE comparative clinical trial was conducted in the non-squamous non-small cell lung cancer (NSCLC) setting.1

*Conducting biosimilar studies in this sensitive population provides scientific evidence supporting extrapolation to less sensitive populations.1


THE FDA HAS APPROVED MVASI™ FOR ALL AVAILABLE AVASTIN® INDICATIONS THROUGH EXTRAPOLATION1,

Extrapolation is the approval of a biosimilar drug for an indication held by the reference drug without direct studies of the biosimilar for that indication.9

MVASI™ TOTALITY OF EVIDENCE1,3,
EXTRAPOLATION9
APPROVED INDICATIONS FOR MVASI™ 2

Comparative clinical study (MAPLE)

Non-squamous non-small cell lung cancer (N = 642)

Clinical pharmacology data

Pharmacokinetics

Analytical and nonclinical studies

Multiple in vitro analytical studies and in vivo analytical studies, including toxicology

Scientific justification for similarity

  • Mechanism of action
  • PK/PD
  • Immunogenicity
  • Safety

EXTRAPOLATION9

The FDA extrapolates these data to consider approval of the biosimilar for all reference drug indications.

APPROVED INDICATIONS FOR MVASI™2

  • Metastatic colorectal cancer (mCRC)
  • Non-squamous non-small cell lung cancer (NSCLC)
  • Recurrent glioblastoma
  • Metastatic renal cell carcinoma (mRCC)
  • Cervical cancer (CC)
 

The MVASI™ biosimilarity program, including choice of NSCLC population, was designed based on FDA guidance.4

*MVASI™ is not currently indicated for ovarian cancer, for which Avastin® has orphan status.10

Totality of evidence establishes structural and functional equivalence, and includes nonclinical evaluation, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and comparative clinical study data.3

PD = pharmacodynamic; PK = pharmacokinetic.


MVASI™ IS THE FIRST FDA-APPROVED ONCOLOGY THERAPEUTIC BIOSIMILAR11

 

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. 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. MVASI™ (bevacizumab-awwb) Prescribing Information, Amgen. 3. 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. 4. US Food and Drug Administration. FDA webinar - overview of the regulatory framework and FDA's guidance for the development and approval of biosimilar and interchangeable products in the US. www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ Biosimilars/ucm610901.htm. Accessed June 8, 2019. 5. Markus R, Chow V, Pan Z, et al.  A phase I, randomized, single-dose study evaluating the pharmacokinetic equivalence of biosimilar ABP 215 and bevacizumab in healthy adult men. Cancer Chemother Pharmacol. 2017;80:755-763. 6. Data on file, Amgen [3.2.R Analytical Similarity Assessment - Biological Activity]. 7. Data on file, Amgen [2.6.6 Toxicology Written Summary]. 8. Data on file, Amgen [2.6.2 Pharmacology Written Summary]. 9. US Food and Drug Administration. Biosimilar development, review, and approval. www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/ucm580429.htm. Accessed June 8, 2019. 10. US Food and Drug Administration. Search: orphan drug designations and approvals. www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=216405. Accessed June 8, 2019. 11. US Food and Drug Administration. FDA approves first biosimilar for cancer treatment. www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm576096.htm. Accessed June 8, 2019.