Bevacizumab biosimilar now PBS-listed

• On 1 June 2021, the bevacizumab biosimilar (MVASI) became available on the PBS..
  The biosimilar has an Unrestricted Benefit listing under Section 100 (Efficient Funding of Chemotherapy).

• The bevacizumab originator (Avastin) is no longer PBS-listed.
  The Unrestricted Benefit listing for the biosimilar ensures a subsidised bevacizumab product remains available for patients currently prescribed this active ingredient as part of their medical treatment.

New listing

On 1 June 2021, the bevacizumab biosimilar (MVASI) was added to the Pharmaceutical Benefits Scheme (PBS) Efficient Funding of Chemotherapy (EFC) Program for public and private hospitals, in the following doses:¹

• bevacizumab 100 mg/4 mL injection, 4 mL vial

• bevacizumab 400 mg/16 mL injection, 16 mL vial

The biosimilar has an Unrestricted Benefit listing with a maximum amount of 1800 mg and 7 repeats.¹

See the PBS website for complete details about each item.

Deleted listings

On 1 June 2021, the bevacizumab originator (Avastin) and all associated items were deleted from the PBS.^1,2

Prior to 1 June 2021, the bevacizumab originator was listed on the PBS as Authority Required or Authority Required (Streamlined).²

Bevacizumab is a recombinant humanised monoclonal antibody. It selectively binds to and inhibits the action of human vascular endothelial growth factor (VEGF), a protein that is essential in the regulation of blood vessel growth in normal tissue and tumours.^3,4

VEGF is an important target of anti-angiogenesis cancer therapy. Inhibiting VEGF activity reduces the vascularisation of tumours, thereby inhibiting tumour growth.^3,5

The originator brand Avastin was TGA-approved for use in Australia in 2005 for the treatment of metastatic colon cancer.^6,7 Two bevacizumab medicines have subsequently also been TGA-approved and determined to be biosimilars to the originator brand Avastin: Zirabev in November 2019 and MVASI in June 2020.^6,8

Both bevacizumab biosimilars (MVASI and Zirabev) have the same TGA-approved indications as the originator brand:^4,9,10

• Metastatic colorectal cancer
• Locally recurrent or metastatic breast cancer
• Advanced, metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC)
• Advanced and/or metastatic renal cell cancer
• Grade IV glioma
• Epithelial ovarian, fallopian tube or primary peritoneal cancer
• Recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer
• Cervical cancer.

At its November 2020 meeting, the Pharmaceutical Benefits Advisory Committee (PBAC) recommended MVASI for PBS listing. The PBAC noted advice from the Lung Foundation Australia provided alongside the submission, that subsidising the use of biosimilars would provide ‘an additional therapy choice to improve patients’ quality of life, reduce costs to the healthcare system and offer greater supply certainty’.¹¹

At the November 2020 meeting, the PBAC recommended the listing of the bevacizumab biosimilar (MVASI) for the same indications and restrictions (Authority Required or Authority Required (Streamlined)) as the bevacizumab originator (Avastin). The listing was recommended on a cost minimisation basis to the originator brand. It was further noted that making the biosimilar available through the PBS was not expected to expand the market, and therefore there would be no net cost to the healthcare system.¹¹

At its March 2021 meeting, the PBAC recommended the listing of bevacizumab (originator and biosimilar) under the EFC schedule be changed to an Unrestricted Benefit, along with a price reduction to offset the likely increase in utilisation due to the change.¹² The PBAC noted this change would allow access to combination treatment with the PBS-listed atezolizumab (eg, for advanced (unresectable) hepatocellular carcinoma), ensuring no patients would be disadvantaged.^12-14

The bevacizumab originator (Avastin) was deleted from the PBS on 1 June 2021.¹ The manufacturer decided to take Avastin off the market in Australia from 30 June 2021 for the 100mg/4mL dose and from 3 December 2021 for the 400mg/16mL dose. These items remain on the market as private prescriptions only until these dates. This decision was due to commercial reasons, according to the Therapeutic Goods Administration (TGA) Medicine Shortages Information Initiative.¹⁵ It was not a reflection on efficacy or safety of the product.

The randomised, double-blind, phase 3 MAPLE trial compared the efficacy and safety of the bevacizumab biosimilar (MVASI) with the bevacizumab originator for 642 people with advanced non-squamous non-small cell lung cancer (NSCLC). Overall, 128 (39%) and 131 (41.7%) patients in the biosimilar and originator group, respectively, had objective responses, with a risk ratio of 0.93 (90% CI, 0.80-1.09). The trial confirmed clinical equivalence after the 90% CI fell within the prespecified equivalence margins. Immunogenicity and pharmacokinetics were comparable between the two groups.¹⁶

A randomised, single-blind, single-dose phase 1 study compared the pharmacokinetic profile of the bevacizumab biosimilar (MVASI) with the bevacizumab originators sourced from the United States (US) and Europe (EU) for 202 healthy adult males. The pharmacokinetic profiles across the three groups were similar, with the 90% CI falling within the prespecified standard pharmacokinetic bioequivalence criteria. Safety, tolerability and immunogenicity were comparable across the three groups.¹⁷

A similar pharmacokinetic comparative study with similar methodology for healthy men in Japan demonstrated consistent results with the previous study.¹⁸

Although there have been no clinical trials demonstrating the efficacy of the bevacizumab biosimilar (MVASI) in other cancer indications, the bevacizumab originator has shown consistent and well-established efficacy across indications through extensive clinical trials and post-market experience.⁵

In alignment with the Government’s commitment to the uptake of biosimilars, prescribers are encouraged to prescribe a biosimilar brand to treatment naïve patients where appropriate.¹⁹

Biological medicines are medicines derived from a living source.²⁰

These medicines now contribute to the management of several chronic diseases, including diabetes, different cancers and a range of autoimmune and inflammatory conditions. In recent years, primary care practitioners will have noted increasing numbers of patients using these medicines, usually prescribed by specialists.

Biological medicines are, however, expensive to develop and manufacture. As these products come off-patent, competing manufacturers can develop highly similar versions of an originator biological medicine, referred to as biosimilar medicines, or simply, ‘biosimilars’. The introduction of biosimilar medicines into the market prompts price reductions and potential savings for the PBS.²⁰

A biosimilar has demonstrable similarity to the originator in physicochemical, biological and immunological characteristics, efficacy and safety, based on comprehensive comparability studies.^21,22

Pharmacovigilance is important to establish the long-term safety and efficacy of all medicines, including biosimilars. No safety signals have emerged following a single switch from reference to biosimilar medicines.²³ 

Patients should be advised that:^1,15

• from 1 June 2021, the bevacizumab originator (Avastin) is no longer available on the PBS,
• from 1 June 2021, the bevacizumab biosimilar (MVASI) is available on the PBS to ensure patients will have continued subsidised access, and
• the bevacizumab originator (Avastin) remains available on the market in Australia until 30 June 2021 (100mg/4mL dose) and 3 December 2021 (400mg/16mL dose) for private prescriptions.

See the TGA medicine shortage reports database for updates.

Here are some discussion points prescribers could cover with their patients when switching from Avastin to MVASI.

MVASI is a biosimilar, which means it has been assessed by the TGA as ‘highly similar’ (biosimilar) and equivalent to Avastin. This means MVASI is as safe and effective as Avastin and provides the same health outcomes.²

The dosage form, strength and administration routes are identical.^4,10 No dose adjustments are required when you transition from Avastin to MVASI.

• NPS MedicineWise Understanding biosimilars
• NPS MedicineWise Avoiding the nocebo effect: talking to your patients about biosimilars
• NPS MedicineWise Biologics, biosimilars and PBS sustainability
• Department of Health Information for consumers: What are biosimilar medicines?
• Department of Health Information for health professionals: What are biosimilar medicines?
• Therapeutic Goods Administration Biosimilar medicines regulation