MVASI

What it is

MVASI is a biosimilar medicine to Avastin (bevacizumab). MVASI is available in 100 mg and 400 mg single dose vials containing 4 mL and 16 mL, respectively, of bevacizumab (25 mg/mL). It is a concentrate for solution for infusion, presented as a clear to slightly opalescent, colourless to pale brown, sterile solution for intravenous infusion. Bevacizumab is a recombinant humanised monoclonal antibody that selectively binds to and neutralises the biologic activity of human vascular endothelial growth factor (VEGF).

Approved indications

— Metastatic colorectal cancer, in combination with fluoropyrimidine-based chemotherapy. — Locally recurrent or metastatic breast cancer in patients in whom an anthracycline-based therapy is contraindicated, in combination with paclitaxel for first-line treatment. — Advanced, metastatic or recurrent non-squamous non-small cell lung cancer, in combination with carboplatin and paclitaxel, for first-line treatment of patients with unresectable disease. — Advanced and/or metastatic renal cell cancer, in combination with interferon alfa-2a. — Grade IV glioma as a single agent, for treatment after relapse or disease progression after standard therapy, including chemotherapy. — Advanced epithelial ovarian, fallopian tube or primary peritoneal cancer (FIGO stages IIIB, IIIC and IV), in combination with carboplatin and paclitaxel, for first-line treatment. — First recurrence of platinum-sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer, in combination with carboplatin and paclitaxel or carboplatin and gemcitabine, in patients who have not received prior bevacizumab or other VEGF-targeted angiogenesis inhibitors. — Recurrent, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer, in combination with paclitaxel, topotecan or pegylated liposomal doxorubicin, in patients who have received no more than two prior chemotherapy regimens and have not received any prior anti-angiogenic therapy. — Persistent, recurrent or metastatic carcinoma of the cervix, in combination with paclitaxel and cisplatin, or paclitaxel and topotecan where cisplatin is not tolerated or not indicated.

Dosing overview

Dosing varies by indication and treatment line. For metastatic colorectal cancer: first-line treatment is 5 mg/kg of body weight given once every 2 weeks or 7.5 mg/kg once every 3 weeks; second-line treatment is 10 mg/kg given every 2 weeks or 15 mg/kg once every 3 weeks. For locally recurrent or metastatic breast cancer: 10 mg/kg once every 2 weeks or 15 mg/kg once every 3 weeks. For advanced, metastatic or recurrent non-squamous non-small cell lung cancer: 15 mg/kg once every 3 weeks in combination with carboplatin and paclitaxel for up to 6 cycles, followed by MVASI as a single agent until disease progression. For advanced and/or metastatic renal cell cancer: 10 mg/kg given once every 2 weeks. For Grade IV glioma: 10 mg/kg once every 2 weeks or 15 mg/kg once every 3 weeks. The initial MVASI dose should be delivered over 90 minutes as an intravenous infusion; if well tolerated, the second infusion may be administered over 60 minutes; if the 60 minute infusion is well tolerated, all subsequent infusions may be administered over 30 minutes.

Key safety warnings

Patients may be at increased risk for gastrointestinal perforation and gallbladder perforation when treated with MVASI, and MVASI should be permanently discontinued in patients who develop gastrointestinal perforation. Gastrointestinal perforations have been reported in clinical trials with an incidence of less than 1% in patients with metastatic breast cancer or non-small cell lung cancer, up to 2% in patients with metastatic colorectal cancer or ovarian cancer, and up to 2.7% in patients with metastatic colorectal cancer including gastrointestinal fistula and abscess. An increased incidence of hypertension was observed in patients treated with bevacizumab, with clinical safety data suggesting that the incidence is likely to be dose-dependent; pre-existing hypertension should be adequately controlled before starting MVASI treatment. Monitoring of blood pressure is recommended during MVASI therapy. MVASI may adversely affect the wound healing process; MVASI therapy should not be initiated for at least 28 days following major surgery or until the surgical wound is fully healed, and should be withheld in patients who experience wound healing complications during therapy until the wound is fully healed. An increased incidence of arterial thromboembolic events has been observed in patients treated with bevacizumab across indications, with the overall incidence ranging up to 5.9% in bevacizumab-containing arms compared with up to 1.7% in chemotherapy control arms. MVASI should be permanently discontinued in patients who develop arterial thromboembolic events. Patients treated with bevacizumab have an increased risk of haemorrhage, especially tumour-associated haemorrhage, and bevacizumab should be permanently discontinued in patients who experience Grade 3 or 4 bleeding during therapy. Patients with non-small cell lung cancer treated with bevacizumab may be at risk for serious, and in some cases fatal, pulmonary haemorrhage/haemoptysis, and patients with recent pulmonary haemorrhage should not be treated with bevacizumab.

Contraindications

MVASI is contraindicated in patients with known hypersensitivity to any components of the product, Chinese hamster ovary cell products or other recombinant human or humanised antibodies.

PBS listing

MVASI 100 mg in 4 mL solution for intravenous infusion is listed on the PBS with 2 items, unrestricted restriction type, at an ex-manufacturer price of A$41.71.

Regulatory history

The TGA approved MVASI as a new biosimilar medicine on 16 January 2019, based on a comprehensive evaluation of quality, nonclinical, and clinical data, which confirmed its biosimilarity to the reference product Avastin, across all proposed indications. MVASI bevacizumab 400 mg/16 mL and 100 mg/4 mL injection concentrated vials were first listed on the ARTG on 30 June 2020. In July 2020, the PBAC recommended new listing as a biosimilar for advanced epithelial ovarian, fallopian tube or primary peritoneal cancer; advanced carcinoma of cervix; relapsed or recurrent glioblastoma; stage IV metastatic non-small cell lung cancer; and metastatic colorectal cancer. In November 2020, the PBAC recommended listing for metastatic colorectal cancer; advanced stage IIIB, IIIC or stage IV epithelial ovarian, fallopian tube, or primary peritoneal cancer; advanced carcinoma of the cervix; and stage IV metastatic non-small cell lung cancer for all indications except relapsed or recurrent glioblastoma.