Bevacizumab

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Bevacizumab, sold under the brand name Avastin among others, is a monoclonal antibody medication used to treat a number of types of cancers and a specific eye disease.<ref name=AHFS2016/><ref name="Avastin FDA label">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> For cancer, it is given by slow injection into a vein (intravenous) and used for colon cancer, lung cancer, ovarian cancer, glioblastoma, hepatocellular carcinoma, and renal-cell carcinoma.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In many of these diseases it is used as a first-line therapy.<ref name=AHFS2016/><ref name="Avastin FDA label" /> For age-related macular degeneration it is given by injection into the eye (intravitreal).<ref name=AHFS2016/>

Common side effects when used for cancer include nose bleeds, headache, high blood pressure, and rash.<ref name=AHFS2016/> Other severe side effects include gastrointestinal perforation, bleeding, allergic reactions, blood clots, and an increased risk of infection.<ref name=AHFS2016/> When used for eye disease side effects can include vision loss and retinal detachment.<ref name=AHFS2016/> Bevacizumab is a monoclonal antibody that functions as an angiogenesis inhibitor.<ref name=AHFS2016/> It works by slowing the growth of new blood vessels by inhibiting vascular endothelial growth factor A (VEGF-A), in other words anti–VEGF therapy.<ref name=AHFS2016/>

Bevacizumab was approved for medical use in the United States in 2004.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name=AHFS2016>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO23rd">Template:Cite book</ref>

Medical uses

Colorectal cancer

Bevacizumab was approved in the United States in February 2004, for use in metastatic colorectal cancer when used with standard chemotherapy treatment (as first-line treatment).<ref name=":1">Template:Cite journal</ref> In June 2006, it was approved with 5-fluorouracil-based therapy for second-line metastatic colorectal cancer.<ref name=":1" />

It was approved by the European Medicines Agency (EMA) in January 2005, for use in colorectal cancer.<ref name="EMA_2005" /><ref name="Avastin EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Bevacizumab has also been examined as an add on to other chemotherapy drugs in people with non-metastatic colon cancer. The data from two large randomized studies showed no benefit in preventing the cancer from returning and a potential to cause harm in this setting.<ref>Template:Cite journal</ref>

In the EU, bevacizumab in combination with fluoropyrimidine-based chemotherapy is indicated for treatment of adults with metastatic carcinoma of the colon or rectum.<ref name="Equidacent EPAR" />

Lung cancer

In 2006, the US Food and Drug Administration (FDA) approved bevacizumab for use in first-line advanced nonsquamous non-small cell lung cancer in combination with carboplatin/paclitaxel chemotherapy. The approval was based on the pivotal study E4599 (conducted by the Eastern Cooperative Oncology Group), which demonstrated a two-month improvement in overall survival in patients treated with bevacizumab (Sandler, et al. NEJM 2004).Template:Citation needed A preplanned analysis of histology in E4599 demonstrated a four-month median survival benefit with bevacizumab for people with adenocarcinoma (Sandler, et al. JTO 2010);Template:Citation needed adenocarcinoma represents approximately 85% of all non-squamous cell carcinomas of the lung.

A subsequent European clinical trial, AVAiL, was first reported in 2009 and confirmed the significant improvement in progression-free survival shown in E4599 (Reck, et al. Ann. Oncol. 2010).Template:Citation needed An overall survival benefit was not demonstrated in patients treated with bevacizumab; however, this may be due to the more limited use of bevacizumab as maintenance treatment in AVAiL versus E4599 (this differential effect is also apparent in the European vs US trials of bevacizumab in colorectal cancer: Tyagi and Grothey, Clin Colorectal Cancer, 2006).Template:Citation needed As an anti-angiogenic agent, there is no mechanistic rationale for stopping bevacizumab before disease progression. Stated another way, the survival benefits achieved with bevacizumab can only be expected when used in accordance with the clinical evidence: continued until disease progression or treatment-limiting side effects.

Another large European-based clinical trial with bevacizumab in lung cancer, AVAPERL, was reported in October 2011 (Barlesi, et al. ECCM 2011).Template:Citation needed First-line patients were treated with bevacizumab plus cisplatin/pemetrexed for four cycles, and then randomized to receive maintenance treatment with either bevacizumab/pemetrexed or bevacizumab alone until disease progression. Maintenance treatment with bevacizumab/pemetrexed demonstrated a 50% reduction in risk of progression vs bevacizumab alone (median PFS: 10.2 vs 6.6 months). Maintenance treatment with bevacizumab/pemetrexed did not confer a significant increase in overall survival vs bevacizumab alone on follow up analysis.<ref>Template:Cite journal</ref>

In the EU, bevacizumab, in addition to platinum-based chemotherapy, is indicated for first-line treatment of adults with unresectable advanced, metastatic or recurrent non-small cell lung cancer other than predominantly squamous cell histology.<ref name="Equidacent EPAR" /> Bevacizumab, in combination with erlotinib, is indicated for first-line treatment of adults with unresectable advanced, metastatic or recurrent non-squamous non-small cell lung cancer with Epidermal Growth Factor Receptor (EGFR) activating mutations.<ref name="Equidacent EPAR" />

Breast cancer

In December 2010, the US Food and Drug Administration (FDA) notified its intention to remove the breast cancer indication from bevacizumab, saying that it had not been shown to be safe and effective in breast cancer patients.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The combined data from four different clinical trials showed that bevacizumab neither prolonged overall survival nor slowed disease progression sufficiently to outweigh the risk it presents to patients. This only prevented Genentech from marketing bevacizumab for breast cancer. Doctors are free to prescribe bevacizumab off label, although insurance companies are less likely to approve off-label treatments.<ref name="FDA breast1">Template:Cite press release</ref><ref name="Breast Cancer">Template:Cite news</ref> In June 2011, an FDA panel unanimously rejected an appeal by Roche. A panel of cancer experts ruled for a second time that Avastin should no longer be used in breast cancer patients, clearing the way for the US government to remove its endorsement from the drug. The June 2011 meeting of the FDA's oncologic drug advisory committee was the last step in an appeal by the drug's maker. The committee concluded that breast cancer clinical studies of patients taking Avastin have shown no advantage in survival rates, no improvement in quality of life, and significant side effects.<ref name=scijul11>Template:Cite journal</ref>

In the EU, bevacizumab in combination with paclitaxel is indicated for first-line treatment of adults with metastatic breast cancer.<ref name="Equidacent EPAR" /> Bevacizumab in combination with capecitabine is indicated for first-line treatment of adults with metastatic breast cancer in whom treatment with other chemotherapy options including taxanes or anthracyclines is not considered appropriate.<ref name="Equidacent EPAR" />

Kidney cancer

In certain kidney cancers, bevacizumab improves the progression free survival time but not survival time. In 2009, the FDA approved bevacizumab for use in metastatic renal cell cancer (a form of kidney cancer).<ref>Template:Cite news</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> following earlier reports of activity<ref>Template:Cite journal</ref> EU approval was granted in 2007.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In the EU, bevacizumab in combination with interferon alfa-2a is indicated for first-line treatment of adults with advanced and/or metastatic renal cell cancer.<ref name="Equidacent EPAR" />

Brain cancers

Bevacizumab slows tumor growth but does not affect overall survival in people with glioblastoma.<ref name=Am2018>Template:Cite journal</ref> The FDA granted accelerated approval for the treatment of recurrent glioblastoma multiforme in May 2009.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> A 2018 Cochrane review deemed there to not be good evidence for its use in recurrences either.<ref name=Am2018/>

Macular degeneration

In the EU, bevacizumab gamma (Lytenava) is indicated for the treatment of neovascular (wet) age-related macular degeneration (nAMD).<ref name="Lytenava EPAR" />

Ovarian cancer

In 2018, the US Food and Drug Administration (FDA) approved bevacizumab in combination with chemotherapy for stage III or IV of ovarian cancer after initial surgical operation, followed by single-agent bevacizumab. The approval was based on a study of the addition of bevacizumab to carboplatin and paclitaxel.<ref name="FDA-ovarian cancer">{{#invoke:citation/CS1|citation |CitationClass=web }} Template:PD-notice</ref> Progression-free survival was increased to 18 months from 13 months.<ref name="FDA-ovarian cancer"/>

In the EU, bevacizumab, in combination with carboplatin and paclitaxel is indicated for the front-line treatment of adults with advanced (International Federation of Gynecology and Obstetrics (FIGO) stages IIIB, IIIC and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer.<ref name="Equidacent EPAR" /> Bevacizumab, in combination with carboplatin and gemcitabine or in combination with carboplatin and paclitaxel, is indicated for treatment of adults with first recurrence of platinum-sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-targeted agents.<ref name="Equidacent EPAR" />

In May 2020, the FDA expanded the indication of olaparib to include its combination with bevacizumab for first-line maintenance treatment of adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency positive status defined by either a deleterious or suspected deleterious BRCA mutation, and/or genomic instability.<ref>Template:Cite press release Template:PD-notice</ref>

Cervical cancer

In the EU, bevacizumab, in combination with paclitaxel and cisplatin or, alternatively, paclitaxel and topotecan in people who cannot receive platinum therapy, is indicated for the treatment of adults with persistent, recurrent, or metastatic carcinoma of the cervix.<ref name="Equidacent EPAR" />

Adverse effects

Bevacizumab inhibits the growth of blood vessels, which is part of the body's normal healing and maintenance. The body grows new blood vessels in wound healing, and as collateral circulation around blocked or atherosclerotic blood vessels. One concern is that bevacizumab will interfere with these normal processes, and worsen conditions like coronary artery disease or peripheral artery disease.<ref>Template:Cite journal</ref>

The main side effects are hypertension and heightened risk of bleeding. Bowel perforation has been reported.<ref>Template:Cite journal</ref> Fatigue and infection are also common.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In advanced lung cancer, less than half of patients qualify for treatment.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Nasal septum perforation and renal thrombotic microangiopathy have been reported.<ref>Template:Cite journal</ref> In December 2010, the FDA warned of the risk of developing perforations in the body, including in the nose, stomach, and intestines.

In 2013, Hoffmann-La Roche announced that the drug was associated with 52 cases of necrotizing fasciitis from 1997 to 2012, of which 17 patients died.<ref>Template:Cite news</ref> About 2/3 of cases involved patients with colorectal cancer, or patients with gastrointestinal perforations or fistulas.

These effects are largely avoided in ophthalmological use since the drug is introduced directly into the eye thus minimizing any effects on the rest of the body.Template:Citation needed

Neurological adverse events include reversible posterior encephalopathy syndrome. Ischemic and hemorrhagic strokes are also possible.<ref>Template:Cite journal</ref>

Protein in the urine occurs in approximately 20% of people. This does not require permanent discontinuation of the drug. Nonetheless, the presence of nephrotic syndrome necessitates permanent discontinuation of bevacizumab.<ref name="PrescribingInformation" />

Mechanism of action

Bevacizumab is a recombinant humanized monoclonal antibody that blocks angiogenesis by inhibiting vascular endothelial growth factor A (VEGF-A).<ref name=Los>Template:Cite journal</ref> VEGF-A is a growth factor protein that stimulates angiogenesis in a variety of diseases, especially in cancer. By binding VEGF-A, bevacizumab should act outside the cell, but in some cases (cervical and breast cancer) it is taken up by cells through constitutive endocytosis.<ref>Template:Cite journal</ref> It also is taken up by retinal photoreceptor cells after intravitreal injection.<ref name="pmid17525217">Template:Cite journal</ref>

Chemistry

Bevacizumab was originally derived from a mouse monoclonal antibody generated from mice immunized with the 165-residue form of recombinant human vascular endothelial growth factor. It was humanized by retaining the binding region and replacing the rest with a human full light chain and a human truncated IgG1 heavy chain, with some other substitutions. The resulting plasmid was transfected into Chinese hamster ovary cells which are grown in industrial fermentation systems.<ref name="EMA_2005">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>Template:Rp

History

Bevacizumab is a recombinant humanized monoclonal antibody and in 2004, it became the first clinically used angiogenesis inhibitor.<ref name=NYT2004>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Its development was based on the discovery of human vascular endothelial growth factor (VEGF), a protein that stimulated blood vessel growth, in the laboratory of Genentech scientist Napoleone Ferrara.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref name=Saga>Template:Cite journal</ref> Ferrara later demonstrated that antibodies against VEGF inhibit tumor growth in mice.<ref>Template:Cite journal</ref> His work validated the hypothesis of Judah Folkman, proposed in 1971, that stopping angiogenesis might be useful in controlling cancer growth.<ref name=Saga/>

Approval

It received its first approval in the United States in 2004, for combination use with standard chemotherapy for metastatic colon cancer.<ref name=PrescribingInformation>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It has since been approved for use in certain lung cancers, renal cancers, ovarian cancers, and glioblastoma multiforme of the brain.Template:Medcn

In 2008, bevacizumab was approved for breast cancer by the FDA, but the approval was revoked on 18 November 2011<ref name=BreastFDA>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="NYT2011">Template:Cite news</ref><ref name="bbc">Template:Cite news</ref> because, although there was evidence that it slowed progression of metastatic breast cancer, there was no evidence that it extended life or improved quality of life, and it caused adverse effects including severe high blood pressure and hemorrhaging.Template:Medcn

In 2008, the FDA gave bevacizumab provisional approval for metastatic breast cancer, subject to further studies. The FDA's advisory panel had recommended against approval.<ref name=nytimesref>Template:Cite news</ref> In July 2010, after new studies failed to show a significant benefit, the FDA's advisory panel recommended against the indication for advanced breast cancer. Genentech requested a hearing, which was granted in June 2011. The FDA ruled to withdraw the breast cancer indication in November 2011. FDA approval is required for Genentech to market a drug for that indication. Doctors may sometimes prescribe it for that indication, although insurance companies are less likely to pay for it.<ref name="NYT2011"/>

The drug remains approved for breast cancer use in other countries, including Australia.<ref>Template:Cite news</ref> It has been funded by the English NHS Cancer Drugs Fund, but in January 2015 it was proposed to remove it from the approved list.<ref>Template:Cite news</ref> It remains on the Cancer Drugs Fund as of March 2023.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Society and culture

Use for macular degeneration

In 2015, there was a fierce debate in the UK and other European countries concerning the choice of prescribing bevacizumab or ranibizumab (Lucentis) for wet AMD.<ref name=BMJ2015pt1>Template:Cite news</ref> In the UK, part of the tension was between on the one hand, both the European Medicines Agency and the Medicines and Healthcare products Regulatory Agency which had approved Lucentis but not Avastin for wet AMD, and their interest in ensuring that doctors do not use medicines off-label when there are other, approved medications for the same indication, and on the other hand, NICE in the UK, which sets treatment guidelines, and has been unable so far to appraise Avastin as a first-line treatment, in order to save money for the National Health Service.<ref name=BMJ2015pt1/> Novartis and Roche (which respectively have marketing rights and ownership rights for Avastin) had not conducted clinical trials to get approval for Avastin for wet AMD and had no intention of doing so.<ref name=BMJ2015pt1/> Further, both companies lobbied against treatment guidelines that would make Avastin a first-line treatment, and when government-funded studies comparing the two drugs were published, they published papers emphasizing the risks of using Avastin for wet AMD.<ref name=BMJ2015pt1/>

In March 2024, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Lytenava (bevacizumab gamma), intended for treatment of neovascular (wet) age-related macular degeneration (nAMD).<ref name="Lytenava EPAR" /><ref>Template:Cite press release</ref> The applicant for this medicinal product is Outlook Therapeutics Limited.<ref name="Lytenava EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Lytenava was approved for medical use in the European Union in May 2024.<ref name="Lytenava EPAR" />

Breast cancer approval

In March 2007, the European Commission approved bevacizumab in combination with paclitaxel for the first-line treatment of metastatic breast cancer.<ref name="Austria-Codex">Template:Cite bookTemplate:Page needed</ref>

In 2008, the FDA approved bevacizumab for use in breast cancer. A panel of outside advisers voted 5 to 4 against approval, but their recommendations were overruled. The panel expressed concern that data from the clinical trial did not show any increase in quality of life or prolonging of life for patients—two important benchmarks for late-stage cancer treatments. The clinical trial did show that bevacizumab reduced tumor volumes and showed an increase in progression free survival time. It was based on this data that the FDA chose to overrule the recommendation of the panel of advisers. This decision was lauded by patient advocacy groups and some oncologists. Other oncologists felt that granting approval for late-stage cancer therapies that did not prolong or increase the quality of life for patients would give license to pharmaceutical companies to ignore these important benchmarks when developing new late-stage cancer therapies.<ref name="nytimesref" />

In 2010, before the FDA announcement, The National Comprehensive Cancer Network (NCCN) updated the NCCN Clinical Practice Guidelines for Oncology (NCCN Guidelines) for Breast Cancer to affirm the recommendation regarding the use of bevacizumab in the treatment of metastatic breast cancer.Template:Citation needed

In 2011, the US Food and Drug Administration removed bevacizumab indication for metastatic breast cancer after concluding that the drug has not been shown to be safe and effective. The specific indication that was withdrawn was for the use of bevacizumab in metastatic breast cancer, with paclitaxel for the treatment of people who have not received chemotherapy for metastatic HER2-negative breast cancer.Template:Citation needed

Counterfeit

In February 2012, Roche and its US biotech unit Genentech announced that counterfeit Avastin had been distributed in the United States.<ref>Template:Cite news</ref> The investigation is ongoing, but differences in the outer packaging make identification of the bogus drugs simple for medical providers. Roche analyzed three bogus vials of Avastin and found they contained salt, starch, citrate, isopropanol, propanediol, t-butanol, benzoic acid, di-fluorinated benzene ring, acetone and phthalate moiety, but no active ingredients of the cancer drug. According to Roche, the levels of the chemicals were not consistent; whether the chemicals were at harmful concentrations could not therefore be determined. The counterfeit Avastin has been traced back to Egypt, and it entered legitimate supply chains via Europe to the United States.<ref>Template:Cite news</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Biosimilars

In July 2014, two pharming companies, PlantForm and PharmaPraxis, announced plans to commercialize a biosimilar version of bevacizumab made using a tobacco expression system in collaboration with the Fraunhofer Center for Molecular Biology.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>Template:Update inline

In September 2017, the US FDA approved Amgen's biosimilar (generic name bevacizumab-awwb, product name Mvasi) for six cancer indications.<ref name="FDA PR 20170914">Template:Cite press release Template:PD-notice</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In January 2018, Mvasi was approved for use in the European Union.<ref name="Mvasi EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In February 2019, Zirabev was approved for use in the European Union.<ref name="Zirabev EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Zirabev was approved for medical use in the United States in June 2019,<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and in Australia in November 2019.<ref name="AU biosimilar" />

In June 2020, Mvasi was approved for medical use in Australia.<ref name="AU biosimilar" />

In August 2020, Aybintio was approved for use in the European Union.<ref name="Aybintio EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In September 2020, Equidacent was approved for use in the European Union.<ref name="Equidacent EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref>

In January 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Alymsys, intended for the treatment of carcinoma of the colon or rectum, breast cancer, non-small cell lung cancer, renal cell cancer, epithelial ovarian, fallopian tube or primary peritoneal cancer, and carcinoma of the cervix.<ref name="Alymsys EPAR" /> Alymsys was approved for medical use in the European Union in March 2021.<ref name="Alymsys EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref>

In January 2021, Onbevzi was approved for medical use in the European Union.<ref name="Onbevzi EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In June 2019, and June 2021, Zirabev was approved for medical use in Canada.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Oyavas was approved for medical use in the European Union in March 2021.<ref name="Oyavas EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Abevmy was approved for medical use in the European Union in April 2021,<ref name="Abevmy EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and in Australia in September 2021.<ref name="Abevmy APM summary" /><ref name="AU biosimilar">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In September 2021, Bambevi was approved for medical use in Canada.<ref name="Bambevi SBD">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Bevacip and Bevaciptin were approved for medical use in Australia in November 2021.<ref name="AU biosimilar" /><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In November 2021, Abevmy and Aybintio were approved for medical use in Canada.<ref name="Abevmy SBD">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="Aybintio SBD">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In April 2022, bevacizumab-maly (Alymsys) was approved for medical use in the United States.<ref name="Alymsys FDA label" />

In August 2022, Vegzelma was approved for medical use in the European Union.<ref name="Vegzelma EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In September 2022, bevacizumab-adcd (Vegzelma) was approved for medical use in the United States.<ref name="Vegzelma FDA label">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In June 2023, Enzene Biosciences launched its bevacizumab biosimilar in India.<ref>Enzene Biosciences Launches Bevacizumab Template:Webarchive 29 June 2023</ref>

Bevacizumab-tnjn (Avzivi) was approved for medical use in the United States in December 2023.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In May 2024, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Avzivi, intended for the treatment of carcinoma of the colon or rectum, breast cancer, non-small cell lung cancer, renal cell cancer, epithelial ovarian, fallopian tube or primary peritoneal cancer and carcinoma of the cervix.<ref name="Avzivi EPAR" /><ref>Template:Cite press release</ref> The applicant for this medicinal product is FGK Representative Service GmbH.<ref name="Avzivi EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Avzivi was approved for medical use in the European Union in July 2024.<ref name="Avzivi EPAR" /><ref name="Avzivi PI">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In April 2025, bevacizumab-nwgd (Jobevne) was approved for medical use in the United States.<ref name="Biocon PR">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Research

A study released in April 2009, found that bevacizumab is not effective at preventing recurrences of non-metastatic colon cancer following surgery.<ref>Template:Cite news</ref>

Bevacizumab has been tested in ovarian cancer where it has shown improvement in progression-free survival but not in overall survival.<ref name="pmid27852039">Template:Cite journal</ref> and glioblastoma multiforme where it failed to improve overall survival.<ref name="pmid28527008">Template:Cite journal</ref><ref name="pmid30119081">Template:Cite journal</ref>

Bevacizumab has been investigated as a possible treatment of pancreatic cancer, as an addition to chemotherapy, but studies have shown no improvement in survival.<ref>Template:Cite journal</ref><ref>Template:Cite book</ref> It may also cause higher rates of high blood pressure, bleeding in the stomach and intestine, and intestinal perforations.Template:Medcn

The drug has also undergone trials as an addition to established chemotherapy protocols and surgery in the treatment of pediatric osteosarcoma,<ref name="pmid28631382">Template:Cite journal</ref> and other sarcomas, such as leiomyosarcoma.<ref name="pmid29759566">Template:Cite journal</ref>

Bevacizumab has been studied as a treatment for cancers that grow from the nerve connecting the ear and the brain.<ref>Template:Cite journal</ref>

Further reading

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External links

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