Bevacizumab

Articles · Refrigerated Storage · Lactation Safety Information · New Medicines ·
409405006

Articles

Refrigerated Storage

Avastin · Roche Products Ltd

Roche Products Ltd
Avastin
25mg/ml concentrate for solution for infusion

Contact Roche Products Ltd in all cases where a deviation from the recommended storage conditions has occurred. Refer to the current BNF for company contact details.

Storage at ambient temperature: not provided by manufacturer

Do not freeze. Keep the vial in the outer carton in order to protect from light.

28th September 2020
London MI Service

Lactation Safety Information

No published evidence of safety
Serious adverse effects reported in adults
Low levels anticipated in milk due to the drug’s properties and likely to be degraded in infant’s GI tract. However, the effects on the infant of even small amounts in breast milk are unknown
16th September 2020

New Medicines

Zirabev · Cancer, multiple types in adults: metastatic colorectal, non-squamous non-small cell lung, renal cell carcinoma, and persistent, recurrent or metastatic cervical cancers

Information

Zirabev
Biosimilar
Pfizer
Pfizer

Development and Regulatory status

Launched
Launched
Approved (Licensed)
July 2020
Jul 20 · Launched in the UK [12].
Nov 19 · Launch not expected until patent of originator product expires [12].
Jul 19 · Pfizer Inc. announced the United States (U.S.) Food and Drug Administration(FDA) has approved bevacizumab-bvzr (Zirabev)[11].
Feb 19 · Approved in EU [10].
Dec 18 · Is also pre-registration in the US [9].
Dec 18 · Recommended for EU approval by CHMP - note that the indications do not include all those of the originator product. The full indications are "Zirabev in combination with fluoropyrimidine-based chemotherapy is indicated for treatment of adult patients with metastatic carcinoma of the colon or rectum. Zirabev in combination with paclitaxel is indicated for first-line treatment of adult patients with metastatic breast cancer. For further information as to human epidermal growth factor receptor 2 (HER2) status, please refer to section 5.1. Zirabev, in addition to platinum-based chemotherapy, is indicated for first-line treatment of adult patients with unresectable advanced, metastatic or recurrent non-small cell lung cancer other than predominantly squamous cell histology. Zirabev in combination with interferon alfa-2a is indicated for first line treatment of adult patients with advanced and/or metastatic renal cell cancer. Zirabev, in combination with paclitaxel and cisplatin or, alternatively, paclitaxel and topotecan in patients who cannot receive platinum therapy, is indicated for the treatment of adult patients with persistent, recurrent, or metastatic carcinoma of the cervix (see section 5.1)". It is proposed that Zirabev be prescribed by physicians experienced in the treatment of cancer.[8].
Dec 18 · The CHMP has adopted a positive opinion, recommending marketing authorization for ZIRABEV™ (bevacizumab) [7].
Mar 18 · Bevacizumab biosimilar has been filed in EU using centralised procedure; assume it to be this product [6].

Category

Monoclonal antibody that inhibits vascular endothelial growth factor (VEGF)
UK incidence of advanced NSCLC is 40 per 100,000 people; 25% are able to have first-line therapy, of these 20-40% may receive second-line therapy.
Cancer, multiple types in adults: metastatic colorectal, non-squamous non-small cell lung, renal cell carcinoma, and persistent, recurrent or metastatic cervical cancers
Intravenous infusion

Trial or other data

Dec 18 · PIII 3 REFLECTIONS B739-03 comparative study demonstrated clinical equivalence and found no clinically meaningful differences between ZIRABEV and Avastin in patients with advanced non-squamous NSCLC [7].
Jul 17 · Pfizer announce positive top-line results from REFLECTIONS B7391003 (NCT02364999) study. RCT (n=719) demonstrated equivalence in primary endpoint of objective response rate of PF-06439535 vs. Avastin, taken in combination with carboplatin/paclitaxel, for the first line treatment of patients with advanced non-squamous NSCLC [4].
Dec 16 · PIII trial comparing PF-6439535 with Avastin (NCT02364999) estimated completion date Dec 17 [3].
Jul 15 · Phase III randomised double blind trial started April 2015 to compare efficacy and safety of bevacizumab biosimilar with originator product in 798 patients in the US. Bevacizumab combined with paclitaxel and carboplatin will be used for first-line treatment of patients with advanced (unresectable, locally-advanced, recurrent or metastatic) non-squamous non-small cell lung cancer. Primary endpoint is response rate at 19 weeks [1].

Evidence based evaluations

Aybintio · Cancer including colorectal, lung, breast, kidney and ovarian

Information

Aybintio
Biosimilar
Samsung Bioepsis
Samsung Bioepsis

Development and Regulatory status

Launched
Launched
Pre-registration (Filed)
October 2020
Oct 20 · Available in the UK, Price = 100mg/4ml x 1 vial =£218.39 400mg/16ml x 1 vial =£831.96. [12,13,14]
Aug 20 · The EC has granted marketing authorization for AYBINTIO® (bevacizumab) for the treatment of the same types of cancer as reference bevacizumab [11].
Jun 20 · Recommended for EU approval by CHMP - approval covers all indications of the originator product: Treatment of adults with metastatic carcinoma of the colon or rectum, metastatic breast cancer, unresectable advanced, metastatic or recurrent non-small cell lung cancer, advanced and/or metastatic renal cell cancer, epithelial ovarian, fallopian tube, or primary peritoneal cancer and persistent, recurrent, or metastatic carcinoma of the cervix [10].
Nov 19 · Samsung Bioepis has announced that FDA have accepted an abbreviated BLA (aBLA) for its bevacizumab biosimilar (SB8) [7].
Jul 19 · Samsung Bioepis announce EMA has accepted MAA [6].
Aug 17 · Patent expiry including paediatric extension 06/20 [3]

Category

VEGF-A inhibitor that can slow the growth of new blood vessels in tumours
Cancer including colorectal, lung, breast, kidney and ovarian
Intravenous infusion

Trial or other data

Dec 18 · PIII trial comparing SB8 with Avastin (NCT02754882) anticipated completion date still Dec 18 [5].
Feb 18 · Recruitment for PIII trial completed Dec 17 [4].
Jan 17 · PIII trial comparing SB8 with Avastin in advanced non small cell lung cancer (NCT02754882) has estimated completion date Dec 2018 [2].
May 16 · PIII trial (EudraCT 2015-004026-34) starting in Europe Russia and Taiwan comparing SB8 with Avastin in 678 patients with metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC). The study will compare efficacy, safety, pharmacokinetics and immunogenicity of the two agents over 24 weeks. Secondary objectives for the trial include evaluation of the efficacy of SB8 compared to Avastin in terms of progression-free survival, overall survival and duration of response [1].

bevacizumab biosimilar (MYL1402O) · Cancer including non-small cell lung cancer and colorectal cancer

Information

bevacizumab biosimilar (MYL1402O)
Biosimilar
Mylan
Mylan

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Pre-registration (Filed)
May 20 · Preregistration for Non-small cell lung cancer (Combination therapy, First-line therapy, Inoperable or Unresectable, Late-stage disease, Metastatic disease, Recurrent) in European Union (IV) before May 2020 [3].
Mar 20 · Mylan announced on 27 February 2020 that the US Food and Drug Administration (FDA) has accepted its application for its bevacizumab biosimilar (MYL 1402O) [1].

Category

Inhibitor of vascular endothelial growth factor A (VEGF-A)
UK incidence of advanced NSCLC is 40 per 100,000 people; 25% are able to have first-line therapy, of these 20-40% may receive second-line therapy.
Cancer including non-small cell lung cancer and colorectal cancer
Intravenous infusion

Trial or other data

Mar 20 · PIII multicenter double-blind, randomized, study to assess the efficacy and safety of MYL-1402O compared with Avastin®, in the first-line treatment of patients with stage IV Non-small cell lung cancer [2]

Oyavas · Cancer, including NSCLC and some other indications

Information

Oyavas
Biosimilar
Thornton & Ross (parent company Stada)
Not Known

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Phase III Clinical Trials
Sep 20 · Stada have in-licensed bevaccizumab biosimilar developed by Mabxience, a Spanish company and Thornton & Ross have the rights to promote it in the UK under the brand name Oyavas [2].
Sep 20 · PIII equivalence trial with Avastin completed Feb 20 [1].
Aug 20 · Currently pre-registration in EU [2].

Category

Vascular endothelial growth factor (VEGF) inhibitor
UK incidence of advanced NSCLC is 40 per 100,000 people; 25% are able to have first-line therapy, of these 20-40% may receive second-line therapy.
Cancer, including NSCLC and some other indications
Intravenous infusion

Trial or other data

Sep 20 · PIII multinational equivalence trial to compare the efficacy and safety of MB02 plus chemotherapy (carboplatin and paclitaxel) versus Avastin® plus chemotherapy (carboplatin and paclitaxel) in subjects with Stage IIIB/IV non-squamous NSCLC (NCT03296163) has completed [1].

bevacizumab biosimilar (BAT1706) · Cancer including advanced non-squamous non-small cell lung cancer (NSCLC)

Information

bevacizumab biosimilar (BAT1706)
Biosimilar
Bio-Thera
Bio-Thera

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

VEGF-A inhibitor that can slow the growth of new blood vessels in tumours
UK incidence of advanced NSCLC is 40 per 100,000 people; 25% are able to have first-line therapy, of these 20-40% may receive second-line therapy.
Cancer including advanced non-squamous non-small cell lung cancer (NSCLC)
Intravenous infusion

bevacizumab biosimilar (CT-P16) · Cancer in adults including metastatic colorectal cancer, metastatic breast cancer, non-small cell lung cancer

Information

bevacizumab biosimilar (CT-P16)
Biosimilar
Celltrion
Celltrion

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

VEGF antagonist
Colorectal cancer is the third most common cancer in the UK after breast and lung cancer, with approximately 40,000 new cases registered each year.
Cancer in adults including metastatic colorectal cancer, metastatic breast cancer, non-small cell lung cancer
Intravenous

bevacizumab biosimilar (ONS-5010) · Wet age-related macular degeneration (AMD) - ophthalmic formulation

Information

bevacizumab biosimilar (ONS-5010)
Biosimilar
Outlook Therapeutics formerly Oncobiologics
Outlook Therapeutics formerly Oncobiologics

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Aug 20 · Based on end-of-Phase 2 discussions with the FDA, Outlook believes that the results from NORSE 1 and NORSE 2, combined with our upcoming NORSE 3 safety study that is designed to ensure an adequate number of patient exposures to ONS-501, will be sufficient to support a new BLA submission in H2 2021 [12].
Aug 20 · Outlook Therapeutics intends to complete development of ONS-5010 for submission to the FDA as a new BLA under the 351(a) PHSA regulatory pathway for the treatment of wet AMD and also has plans to submit for regulatory approvals in Europe, the UK and Japan, as well as other countries [12].
Aug 20 · Phase returned to PIII due to uncertainty about whether this product was filed in EU in June 2020 [11].
Jun 20 · Company is also planning to file in the US for wAMD and other retinal diseases in 2021 [10].
Jun 20 · Filed in EU via centralised procedure [7].
Jun 20 · Outlook currently intends to commercialize ONS-5010 in both vials and single-use pre-filled syringes [5].
Sep 19 · Outlook therapeutics plan to submit ONS-5010 for regulatory approval in multiple markets in 2020 [4].
Apr 19 · The company plan to submit ONS-5010 for regulatory approval in multiple markets in 2020 [3].
Nov 18 · Oncobiologics is developing ONS-5010 as an innovative therapy and not using the biosimilar drug development pathway [1].

Category

Vascular endothelial growth factor (VEGF) inhibitor
The estimated prevalence of AMD in the UK is 4.8% of those over 65 years of age and 12.2% of those aged 80 years or more. There are around 70,000 new diagnoses in the UK each year [2].
Wet age-related macular degeneration (AMD) - ophthalmic formulation
Intravitreal

Trial or other data

Sep 20 · PIII NORSE-2 study (NCT03834753) is now due to complete collection of primary outcome data in Jun 2021. PIII NORSE-3 study (NCT04516278) is a 3-month study that will evaluate the safety of ophthalmic bevacizumab in subjects diagnosed with a retinal condition that would benefit from treatment with intravitreal injection of bevacizumab, including: exudative age-related macular degeneration, diabetic macular edema, or branch retinal vein occlusion. 180 adults will be recruited and data collection is expected to complete Mar 21 [13].
Aug 20 · Outlook Therapeutics expects to report pivotal safety and efficacy data from NORSE 2 in Q3 2021 [12].
Aug 20 · Top-line results announced demonstrating safety and efficacy of ONS-5010 for the treatment of wet AMD from the NORSE-1 clinical study. Overall, 2 of 25 (8%) patients on ONS-5010 achieved > 15 letters best corrected visual acuity (BCVA) at Month 11 compared to 5 of 23 (22%) patients on the ranibizumab arm, with no statistical differences between ranibizumab and ONS-5010. The results from NORSE 1 met our proof-of-concept expectations and, importantly, validate our confidence in the design of our ongoing NORSE 2 trial [12].
Jun 20 · PIII trial NORSE-1 (NCT03844074) due to complete August 2020, and NORSE 2 (NCT03834753) due to complete Dec 20 [6].
Sep 19 · PIII trial NORSE-1 has completed patient recruitment, this is evaluating ONS-5010 against ranibizumab (Lucentis®) for wet AMD [4].
Apr 19 · ONS-5010-002 is the second PIII clinical trialsevaluating ONS-5010 against ranibizumab (Lucentis®) for wet AMD and will enroll approximately 180 patients (90 in each arm). Patients will be treated for 11 months, the primary outcome is a statistically significant improvement in mean visual acuity of five letters or more for ONS-5010 over ranibizumab [3].
Nov 18 · Oncobiologics has begun dosing patients in its first clinical trial for ONS-5010 in patients with wet age related macular degeneration (wet AMD) [1].

Equidacent · Cancer, including colon, rectum, breast, renal and non-small cell lung cancer

Information

Equidacent
Biosimilar
Centus Biotherapeutics
Centus Biotherapeutics

Development and Regulatory status

Licensed but not launched
Licensed but not launched
None
Nov 20 · Plans for UK launch not decided [8].
Sep 20 · The EC has granted the marketing authorization for FKB238, bevacizumab biosimilar [7].
Jul 20 · Recommended for EU approval by CHMP - approval covers all indications of the originator product [6].
Nov 19 · Currently pre-registration in the EU [5].

Category

Vascular endothelial growth factor-A (VEGF-A) inhibitor
Colorectal cancer is the third most common cancer in the UK after breast and lung cancer, with approximately 40,000 new cases registered each year.
Cancer, including colon, rectum, breast, renal and non-small cell lung cancer
Intravenous infusion

Trial or other data

Dec 18 · PIII trial Evaluation of FKB238 and Avastin in Patients With Advanced/Recurrent Non-squamous Non-small Cell Lung Cancer (AVANA; NCT02810457) active not recruiting [4].
Jun 16 · PIII trial started comparing FKB-238 with originator bevacizumab Avastin in patients with advanced/recurrent non squamous non-small cell lung cancer (NCT02810457), estimated primary completion date Jun 2019 [2].
Nov 14 · PI trial started in Europe [1].

Mvasi · Cancer, multiple types in adults: metastatic colorectal, non-squamous non-small cell lung, renal cell carcinoma, and persistent, recurrent or metastatic cervical cancers

Information

Mvasi
Biosimilar
Amgen
Amgen

Development and Regulatory status

Licensed but not launched
Licensed but not launched
Launched
Jun 20 · Company cannot confirm the date of availability of ABP215 in the UK [14].
Jan 19 · Has been available in the US since Oct 17 [13].
Jan 18 · Approved for the treatment of various cancers, combined with other agents: metastatic carcinoma of the colon, rectum, breast; unresectable advanced, metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC); advanced/metastatic renal cell cancer; epithelial ovarian, fallopian tube, or primary peritoneal cancer; metastatic carcinoma of the cervix [12].
Nov 17 · Amgen also submitted an MAA for a bevacizumab biosimilar called Kyomarc but withdrew the application. Based on the review of the data at the time of the withdrawal, the CHMP had no major concerns and was of the provisional opinion that Kyomarc could have been approved for the treatment of the cancers listed above - see EMA questions and answers [11].
Nov 17 · CHMP recommends EU approval for various cancer indications [11].
Sep 17 · Approved in US [10].
Aug 17 · Patent expiry including paediatric extension 06/20 [9].
Jul 17 · FDA’s Oncologic Drugs Advisory Committee voted 17-0 to recommend approval of ABP 215 in each of the approved indications [8].
Dec 16 · Marketing Authorisation Application submitted to the EMA, based on non-clinical data plus the results of the PIII clinical trial. Amgen-Allergan believe that this will be the first bevacizumab biosimilar application submitted to the EMA [7].
Nov 16 · Filed in US. Amgen-Allergan based the application in part on a PIII study of patients with non-squamous NSCLC [6].
Nov 15 · Reference product primary conditions are colorectal cancer, non-squamous NSCLC, glioblastoma, RCC, breast cancer & ovarian cancer [5].
Sep 15 · The PIII trial reported to meet its primary outcome involved 642 patients. Amgen believes the positive NSCLC study will eventually support ABP 215´s approval in all 6 cancers for which Avastin is already indicated. But Amgen and Allergan will have to wait until Avastin´s patents run out, not expected until 2019 in the US and 2022 in Europe [4].

Category

VEGF antagonist
Cancer, multiple types in adults: metastatic colorectal, non-squamous non-small cell lung, renal cell carcinoma, and persistent, recurrent or metastatic cervical cancers
Intravenous

Trial or other data

Sep 15 · Trial results announced. The PIII trial of biosimilar ABP-215 hit primary and secondary endpoints, showing clinical equivalence in the objective response rate and comparable safety to Avastin [3]
Sep 15 · Final data collection date for primary outcome measure was July 2015 [2]
Feb 14 · NCT01966003 is a randomized, double-blind, PIII study of ABP 215 vs bevacizumab in 620 subjects with advanced NSCLC. The primary outcome is objective response rate (ORR) up to 19 weeks. The study started Oct 13 and is due to complete Feb 16 [1]

Evidence based evaluations