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Onbevzi (bevacizumab)
Sponsor
ARTGs
Device/Product name
Onbevzi
Active Ingredient
Bevacizumab
Date of decision
Published
Submission type
New Biosimilar
Decision
Approved
What was the decision based on
The decision was based on quality (chemistry and manufacturing), nonclinical (pharmacology and toxicology) and clinical (pharmacology, safety and efficacy) information submitted by the sponsor. The benefit-risk profile of Onbevzi was considered favourable for the therapeutic use approved.
A Phase I study in healthy male subjects demonstrated the similarity between Onbevzi and Avastin in terms of pharmacokinetic properties (drug absorption, distribution, metabolism, and excretion) while the steady-state serum concentration data in a clinical Phase III study provided evidence for the pharmacokinetic similarity in a representative patient population (metastatic or recurrent non-squamous NSCLC). The ability of Onbevzi to exert the same therapeutic effect and have the same safety profile as EU Avastin was demonstrated in a clinical Phase III study where Onbevzi and EU Avastin were compared in patients with metastatic or recurrent non-squamous NSCLC using "the overall response rate (ORR)" as the study endpoint. The ORR was equivalent in both groups.
A Phase I study in healthy male subjects demonstrated the similarity between Onbevzi and Avastin in terms of pharmacokinetic properties (drug absorption, distribution, metabolism, and excretion) while the steady-state serum concentration data in a clinical Phase III study provided evidence for the pharmacokinetic similarity in a representative patient population (metastatic or recurrent non-squamous NSCLC). The ability of Onbevzi to exert the same therapeutic effect and have the same safety profile as EU Avastin was demonstrated in a clinical Phase III study where Onbevzi and EU Avastin were compared in patients with metastatic or recurrent non-squamous NSCLC using "the overall response rate (ORR)" as the study endpoint. The ORR was equivalent in both groups.
What steps were involved in the decision process
Registration timeline
The following table summarises the key steps and dates for this application.
| Description | Date |
|---|---|
| Submission dossier accepted and first round evaluation commenced | 30 November 2021 |
| Delegate’s Overall benefit-risk assessment and request for Advisory Committee advice | 29 August 2022 |
| Advisory Committee meeting | 6 and 7 October 2022 |
| Registration decision (Outcome) | 9 January 2024 |
| Completion of administrative activities and registration on ARTG | 24 January 2024 |
| Number of working days from submission dossier acceptance to registration decision* | 222 |
*Statutory timeframe for standard applications is 255 working days
Date of entry onto ARTG
Black triangle scheme
No
Dose forms
Solution for infusion
Strength
100 mg/4 mL and 400 mg/16 mL
Containers
Single-dose vial
Pack sizes
One
Routes of administration
Intravenous infusion
Dosage
Metastatic Colorectal Cancer
The recommended dose of Onbevzi, administered as an IV infusion, is as follows:
First-line treatment: 5 mg/kg of body weight given once every 2 weeks or 7.5 mg/kg of body weight given once every 3 weeks.
Second-line treatment: 10 mg/kg of body weight given every 2 weeks or 15 mg/kg of body weight given once every 3 weeks.
It is recommended that Onbevzi treatment be continued until progression of the underlying disease.
Locally recurrent or metastatic Breast Cancer
The recommended dose of Onbevzi is 10 mg/kg of body weight given once every 2 weeks or 15 mg/kg of body weight given once every 3 weeks as an IV infusion.
It is recommended that Onbevzi treatment be continued until progression of the underlying disease.
Advanced, metastatic or recurrent non-squamous Non-Small Cell Lung Cancer
The recommended dose of Onbevzi in combination with carboplatin and paclitaxel is 15 mg/kg of body weight given once every 3 weeks as an IV infusion.
Onbevzi is administered in addition to carboplatin and paclitaxel for up to 6 cycles of treatment followed by Onbevzi as a single agent until disease progression.
Advanced and/or Metastatic Renal Cell Cancer
The recommended dose of Onbevzi is 10 mg/kg given once every 2 weeks as an IV infusion.
It is recommended that Onbevzi treatment be continued until progression of the underlying disease.
Onbevzi should be given in combination with IFN alfa-2a (Roferon-A). The recommended IFN alfa-2a dose is 9 MIU three times a week, however, if 9 MIU is not tolerated, the dosage may be reduced to 6 MIU and further to 3 MIU three times a week
Grade IV Glioma
The recommended dose of Onbevzi is 10 mg/kg of body weight given once every 2 weeks or 15 mg/kg of body weight given once every 3 weeks as an IV infusion.
It is recommended that Onbevzi treatment be continued until progression of the underlying disease.
Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer
The recommended dose of Onbevzi administered as an IV infusion is as follows:
First line treatment: 15 mg/kg of body weight given once every 3 weeks in combination with carboplatin and paclitaxel for up to 6 cycles of treatment, followed by continued use of Onbevzi as single agent.
It is recommended that Onbevzi treatment be continued for a total of 15 months therapy or until disease progression, whichever occurs earlier.
Treatment of recurrent disease:
Platinum sensitive: 15 mg/kg of body weight given once every 3 weeks in combination with carboplatin and paclitaxel for 6 cycles (up to 8 cycles) followed by continued use of Onbevzi as a single agent until disease progression. Alternatively, 15 mg/kg of body weight given once every 3 weeks in combination with carboplatin and gemcitabine for 6 cycles (up to 10 cycles), followed by continued use of Onbevzi as single agent until disease progression.
Platinum resistant: 10 mg/kg body weight given once every 2 weeks when administered in combination with one of the following agents – paclitaxel or topotecan (given weekly) or pegylated liposomal doxorubicin. Alternatively, 15 mg/kg every 3 weeks when administered in combination with topotecan given on days 1 to 5, every 3 weeks.
It is recommended that treatment be continued until disease progression.
Cervical Cancer
Onbevzi is administered in combination with paclitaxel and cisplatin or, if cisplatin is not tolerated or not indicated, paclitaxel and topotecan. The recommended dose of Onbevzi is 15 mg/kg of body weight given once every 3 weeks as an IV infusion.
It is recommended that Onbevzi treatment be continued until progression of the underlying disease.
For further information refer to the Product Information.
Pregnancy category
D
Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.
The use of any medicine during pregnancy requires careful consideration of both risks and benefits by the treating health professional. The pregnancy database must not be used as the sole basis of decision making in the use of medicines during pregnancy. The TGA does not provide advice on the use of medicines in pregnancy for specific cases. More information is available from obstetric drug information services in your state or territory.
Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.
The use of any medicine during pregnancy requires careful consideration of both risks and benefits by the treating health professional. The pregnancy database must not be used as the sole basis of decision making in the use of medicines during pregnancy. The TGA does not provide advice on the use of medicines in pregnancy for specific cases. More information is available from obstetric drug information services in your state or territory.
What was approved
Onbevzi (bevacizumab) was approved for the following therapeutic use:
Metastatic Colorectal Cancer
Onbevzi (bevacizumab) in combination with fluoropyrimidine-based chemotherapy is indicated for the treatment of patients with metastatic colorectal cancer.
Locally recurrent or metastatic Breast Cancer
Onbevzi (bevacizumab) in combination with paclitaxel is indicated for the first-line treatment of metastatic breast cancer in patients in whom an anthracycline-based therapy is contraindicated (see Section 5.1 Clinical Trials).
Advanced, metastatic or recurrent non-squamous Non-Small Cell Lung Cancer (NSCLC)
Onbevzi (bevacizumab), in combination with carboplatin and paclitaxel, is indicated for first-line treatment of patients with unresectable advanced, metastatic or recurrent, non-squamous, non-small cell lung cancer.
Advanced and/or metastatic Renal Cell Cancer
Onbevzi (bevacizumab) in combination with interferon alfa-2a is indicated for treatment of patients with advanced and/or metastatic renal cell cancer.
Grade IV Glioma
Onbevzi (bevacizumab) as a single agent, is indicated for the treatment of patients with Grade IV glioma after relapse or disease progression after standard therapy, including chemotherapy.
Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer
Onbevzi (bevacizumab) in combination with carboplatin and paclitaxel, is indicated for first-line treatment of patients with advanced (FIGO stages IIIB, IIIC and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer. Recurrent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer Onbevzi (bevacizumab), in combination with carboplatin and paclitaxel or in combination with carboplatin and gemcitabine, is indicated for the treatment of patients with first recurrence of platinum-sensitive, epithelial ovarian, fallopian tube, or primary peritoneal cancer who have not received prior bevacizumab or other VEGF-targeted angiogenesis inhibitors.
Onbevzi (bevacizumab) in combination with paclitaxel, topotecan or pegylated liposomal doxorubicin is indicated for the treatment of patients with recurrent, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received no more than two prior chemotherapy regimens and have not received any prior anti-angiogenic therapy including bevacizumab.
Cervical Cancer
Onbevzi (bevacizumab) in combination with paclitaxel and cisplatin is indicated for the treatment of persistent, recurrent or metastatic carcinoma of the cervix. Onbevzi (bevacizumab) in combination with paclitaxel and topotecan is an acceptable alternative where cisplatin is not tolerated or not indicated.
What is this medicine and how does it work
Onbevzi is a biosimilar medicine to Avastin (bevacizumab). Bevacizumab is a recombinant humanised monoclonal antibody that selectively binds to and neutralises the biologic activity of human vascular endothelial growth factor (VEGF) by binding to its receptors, Flt-1 and KDR, on the surface of endothelial cells. Neutralising the biologic activity of VEGF reduces blood vessel formation in tumours, thereby inhibiting tumour growth. Administration of bevacizumab to mice transplanted with human tumour cells resulted in extensive anti-tumour activity, including against colon, breast, pancreas and prostate cancer cells. Microvascular permeability (blood vessel "leakiness") was reduced potentially resulting in inhibition of metastatic disease (when tumour cells break away from the primary site, travel through the blood or lymph system, and form new tumors at a new site in the body).
What post-market commitments will the sponsor undertake
Laboratory testing & compliance with Certified Product Details (CPD).
All batches of ONBEVZI supplied in Australia must comply with the product details and specifications approved during evaluation and detailed in the Certified Product Details (CPD).
When requested by the TGA, the Sponsor should be prepared to provide product samples, specified reference materials and documentary evidence to enable the TGA to conduct laboratory testing on the Product. Outcomes of laboratory testing are published biannually in the TGA Database of Laboratory Testing Results and periodically in testing reports on the TGA website.
Certified Product Details
The CPD, as described in Guidance 7: Certified Product Details of the Australian Regulatory Guidelines for Prescription Medicines (ARGPM) for the above products should be provided upon registration of these therapeutic goods. In addition, an updated CPD should be provided when changes to finished product specifications and test methods are approved in a Category 3 application or notified through a self-assessable change.
Further information
The latest Product Information (PI) and Consumer Medicines Information (CMI) can be found by searching the Australian Register of Therapeutic Goods (ARTG).
Australian Public Assessment Reports (AusPARs) can be found by searching our AusPAR dataset.
The latest news and updates regarding therapeutic goods regulation can be found on our news page.