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® 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 or 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

*Adequately sensitive to detect clinically meaningful differences between the reference product and the proposed biosimilar, should they exist.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
 

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

*MVASI® is not currently indicated for hepatocellular carcinoma, for which Avastin® has orphan status.10-12

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 BIOSIMILAR13

 

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, including but not limited to anaphylactoid/anaphylactic reactions, have occurred. In clinical studies, 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
  • In Stage III or IV OC after primary surgery, 608 patients received CP+Avastin→Avastin, 607 patients received CP+Avastin→PBO, and 602 patients received CP+PBO→PBO. Grade 3–4 adverse reactions occurring at a higher incidence (≥2%) in either of the Avastin arms vs the chemotherapy only arm were fatigue (CP+Avastin→Avastin, 9%; CP+Avastin→PBO, 6%; CP+PBO→PBO, 6%), hypertension (CP+Avastin→Avastin, 10%; CP+Avastin→PBO, 6%; CP+PBO→PBO, 2%), platelet count decreased (CP+Avastin→Avastin, 21%; CP+Avastin→PBO, 20%; CP+PBO→PBO, 15%), and white blood cell count decreased (CP+Avastin→Avastin, 51%; CP+Avastin→PBO, 53%; CP+PBO→PBO, 50%)
  • In platinum-sensitive recurrent OC, Grade 3 or 4 adverse reactions in the OCEANS study occurring at a higher incidence (≥2%) in 247 patients receiving Avastin plus carboplatin and gemcitabine (chemotherapy), compared to 233 patients receiving placebo plus chemotherapy, were thrombocytopenia (40% vs 34%), nausea (4% vs 1.3%), fatigue (6% vs 4%), headache (4% vs 0.9%), proteinuria (10% vs 0.4%), dyspnea (4% vs 1.7%), epistaxis (5% vs 0.4%), and hypertension (17% vs 0.9%)
  • In platinum-sensitive recurrent OC, Grade 3 or 4 adverse reactions in the GOG-0213 study occurring at a higher incidence (≥2%) in 325 patients receiving Avastin plus carboplatin and paclitaxel (chemotherapy), compared to 332 patients receiving chemotherapy alone, were hypertension (11% vs 0.6%), fatigue (8% vs 3%), febrile neutropenia (6% vs 3%), proteinuria (8% vs 0%), abdominal pain (6% vs 0.9%), hyponatremia (4% vs 0.9%), headache (3% vs 0.9%), and pain in extremity (3.4% vs 0%)
  • In platinum-resistant recurrent OC, Grade 3–4 adverse reactions in AURELIA occurring at a higher incidence (≥2%) in 179 patients receiving Avastin plus chemotherapy, compared to 181 patients receiving chemotherapy alone, were hypertension (6.7% vs 1.1%) and palmar-plantar erythrodysaesthesia syndrome (4.5% vs 1.7%)

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).

MVASI®, in combination with carboplatin and paclitaxel, followed by MVASI as a single agent, is indicated for the treatment of patients with stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer following initial surgical resection (OC).

MVASI®, in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan, is indicated for the treatment of patients with platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who received no more than 2 prior chemotherapy regimens (OC).

MVASI®, in combination with carboplatin and paclitaxel, or with carboplatin and gemcitabine, followed by MVASI as a single agent, is indicated for the treatment of patients with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer (OC).

MVASI® is a trademark of Amgen, Inc.

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
    • Non-GI fistulae (<1% to 1.8%, highest in patients with cervical cancer)
Avastin® (bevacizumab) is a registered trademark of Genentech USA, Inc.

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 March 2, 2020. 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 March 2, 2020. 5. Markus R, Chow V, Pan Z, Hanes V. 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 March 2, 2020. 10. US Food and Drug Administration. Search: orphan drug designations and approvals. www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=216405. Accessed March 2, 2020. 11. US Food and Drug Administration. Search: orphan drug designations and approvals. www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=318010. Accessed March 2, 2020. 12. US Food and Drug Administration. Search: orphan drug designations and approvals. www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=317810. Accessed March 2, 2020. 13. US Food and Drug Administration. FDA approves first biosimilar for cancer treatment. www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm576096.htm. Accessed March 2, 2020.