| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Humanized (frommouse) |
| Target | CD20 |
| Clinical data | |
| Trade names | Gazyva, Gazyvaro |
| Other names | afutuzumab,[1] GA101 |
| AHFS/Drugs.com | Monograph |
| License data | |
| Pregnancy category | |
| Routes of administration | Intravenous infusion |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Eliminationhalf-life | 28.4 days |
| Identifiers | |
| CAS Number | |
| DrugBank |
|
| ChemSpider |
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| UNII | |
| KEGG |
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| Chemical and physical data | |
| Formula | C6512H10060N1712O2020S44 |
| Molar mass | 146064.72 g·mol−1 |
 N Y (what is this?) (verify) | |
Obinutuzumab, sold under the brand nameGazyva among others, is a humanized anti-CD20monoclonal antibody used as a treatment for cancer and activelupus nephritis.[4][5][6] It was originated by GlycArt Biotechnology AG and developed byRoche.[citation needed]
As of 2015, obinutuzumab was being used in combination withchlorambucil as a first-line treatment forchronic lymphocytic leukemia.[4][7] One more recent study has shown deeper and longer-lasting remissions through fixed-duration treatment regimens in combination withvenetoclax.[8][non-primary source needed]
It is also used in combination withbendamustine followed by obinutuzumab monotherapy for the treatment of people withfollicular lymphoma as a second line treatment to a regimen containing rituximab.[4][9]
Obinutuzumab was not tested in pregnant women.[4]
Obinutuzumab has twoblack box warnings:hepatitis B reactivation andprogressive multifocal leukoencephalopathy.[7][4]
In the clinical trial of obinutuzumab in combination with chlorambucil, participants experienced infusion reactions (69%; 21% grade 3/4), neutropenia (40%; 34% grade 3/4), thrombocytopenia (15%; 11% grade 3/4), anemia (12%), and pyrexia and cough (10% each). More than 20% of subjects had abnormal lab tests including low calcium and sodium, high potassium, increases in serum creatinine and liver function tests, and low albumin levels.[7]
Obinutuzumab is recently reported to be safe and effective in some autoimmune diseases affecting the kidneys. It is a promising treatment of renal diseases with proteinuria, in particular patients with resistance or partial response to rituximab.[10] A single low-dose infusion of obinutuzumab, found to be effective and safe in inducing prolonged remission in children with steroid-dependent or frequently relapsing nephrotic syndrome. This effect is particularly shown in children who have rituximab resistance or relapse after rituximab. The tolerance profile of obinutuzumab is comparable to rituximab.[11] Similar promising results is shown in adults with membranoproliferative glomerulonephritis treated with obinutuzumab after resistance to rituximab, tacrolimus and cyclophosphamide. Furthermore, obinutuzumab showed sustained clinical benefit through 2 years in patients with class III and IV Proliferative Lupus Nephritis compared to rituximab.[10]
Obinutuzumab is afully humanized monoclonal antibody that binds to anepitope on CD20 that partially overlaps with the epitope recognized byrituximab.[7]
GlycArt's technology platform allowed control of proteinglycosylation; the cells in which obinutuzumab isproduced wereengineered to overexpress two glycosylation enzymes,MGAT3 and Golgimannosidase 2, whichreduce the amount of fucose attached to the antibody, which in turn increases the antibody's ability to activatenatural killer cells.[12][13]
Details of the antibody's structure are disclosed in the 2008 WHO INN naming proposal.[14]
Obinutuzumab was created by scientists at GlycArt Biotechnology, which had been founded in 2000 as a spin-out company of theSwiss Federal Institute of Technology in Zurich to developafucosylated monoclonal antibodies; GA101 was one of its lead products when it was acquired by Roche in 2005.[15][16][17]
Roche developed the drug in the US through its US subsidiary, Genentech, and in Japan through its Japanese subsidiary, Chugai. Genentech partnered withBiogen Idec to explore the use of the drug forprimary biliary cirrhosis but as of 2014 it appeared the development in that indication had halted.[17]
In November 2013, the USFood and Drug Administration (FDA) approved obinutuzumab in combination withchlorambucil as a first-line treatment forchronic lymphocytic leukemia, and was the first drug withbreakthrough therapy designation to gain approval.[18][19]
In October 2014,NICE announced thatNHS England would not fund use of the drug, due to data uncertainties in Roche's application.[20] In June 2015, NICE announced that it would fund restricted use of the drug.[21]
In their final recommendation of obinutuzumab, in the January 2015 Pan-Canadian Oncology Drug Review (pERC) for treatment of chronic lymphocytic leukemia, published by theCanadian Agency for Drugs and Technologies in Health, the list price of obinutuzumab provided by the manufacturerHoffmann-La Roche was $CDN 5,275.54 per 1,000 mg vial. At the recommended dose obinutuzumab costs $15,826.50" for the first 28-day cycle and "$5275.50 per 28 day cycle for subsequent cycles."[22]
In February 2016, obinutuzumab was approved by the FDA under thePriority Review program for use in combination withbendamustine followed by obinutuzumab monotherapy for the treatment of patients withfollicular lymphoma as a secondline treatment to a regimen containing rituximab.[9]
In January 2019, the USFood and Drug Administration (FDA) approvedibrutinib in combination with obinutuzumab for people withchronic lymphocytic leukemia/small lymphocytic lymphoma who have not received prior treatment.[23]
In October 2025, the USFood and Drug Administration (FDA) approved obinutuzumab for the treatment of adult patients with activelupus nephritis who are receiving standard therapy, making it the first anti-CD20 monoclonal antibody approved for this indication.[6]
As of 2014 clinical trials had been conducted exploring the use of obinutuzumab as a second line monotherapy in relapsed/refractorychronic lymphocytic leukemia, as a monotherapy for relapsed/refractorynon-Hodgkin lymphoma in people who had high expression of CD20; and in combination withCHOP chemotherapy as a first line treatment for people with advanced CD20-positivediffuse large B-cell lymphoma.[17] It was called GA101 during research.[citation needed]
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