Obinutuzumab
Humanized (from mouse) | |
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Target | CD20 |
Clinical data | |
Trade names | Gazyva, Gazyvaro |
Other names | afutuzumab,[1] GA101 |
AHFS/Drugs.com | Monograph |
License data |
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Pregnancy category |
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Intravenous infusion | |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Elimination half-life | 28.4 days |
Identifiers | |
CAS Number | |
DrugBank | |
ChemSpider |
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UNII | |
KEGG | |
Chemical and physical data | |
Formula | C6512H10060N1712O2020S44 |
Molar mass | 146064.72 g·mol−1 |
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Obinutuzumab, sold under the brand name Gazyva among others, is a humanized anti-
Medical uses
Obinutuzumab is used in combination with chlorambucil as a first-line treatment for chronic lymphocytic leukemia.[5][7]
It is also used in combination with bendamustine followed by obinutuzumab monotherapy for the treatment of people with follicular lymphoma as a second line treatment to a regimen containing rituximab.[5][8]
It was not tested in pregnant women.[5]
Side effects
Obinutuzumab has two black box warnings: hepatitis B reactivation and progressive multifocal leukoencephalopathy.[7][5]
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 in difficult nephropathies
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.[9] 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.[10] 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.[11]
Chemistry
Obinutuzumab is a fully humanized monoclonal antibody that binds to an epitope on CD20 that partially overlaps with the epitope recognized by rituximab.[7]
GlycArt's technology platform allowed control of protein
Details of the antibody's structure are disclosed in the 2008 WHO INN naming proposal.[14]
History
Obinutuzumab was created by scientists at GlycArt Biotechnology, which had been founded in 2000 as a spin-out company of the Swiss Federal Institute of Technology in Zurich to develop afucosylated 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 with
In November 2013, the US Food and Drug Administration (FDA) approved obinutuzumab in combination with chlorambucil as a first-line treatment for chronic lymphocytic leukemia, and was the first drug with breakthrough therapy designation to gain approval.[18][19]
In October 2014,
In their final recommendation of obinutuzumab, in the January 2015 Pan-Canadian Oncology Drug Review (pERC) for treatment of chronic lymphocytic leukemia, published by the
In February 2016, obinutuzumab was approved by the FDA under the
In January 2019, the US
Research
As of 2014 clinical trials had been conducted exploring the use of obinutuzumab as a second line monotherapy in relapsed/refractory chronic lymphocytic leukemia, as a monotherapy for relapsed/refractory non-Hodgkin lymphoma in people who had high expression of CD20; and in combination with CHOP chemotherapy as a first line treatment for people with advanced CD20-positive diffuse large B-cell lymphoma.[17] It was called GA101 during research.
References
- ^ WHO Drug Information, Vol. 23, No. 2, 2009 Proposed INN: List 101 Archived 3 March 2016 at the Wayback Machine, p 176
- ^ a b https://www.guildlink.com.au/gc/ws/ro/pi.cfm?product=ropgazyv10515 Archived 8 January 2023 at the Wayback Machine [bare URL]
- FDA. Retrieved 22 October 2023.
- ^ "Prescription medicines: registration of new chemical entities in Australia, 2014". Therapeutic Goods Administration (TGA). 21 June 2022. Archived from the original on 10 April 2023. Retrieved 10 April 2023.
- ^ a b c d e f "Gazyva- obinutuzumab injection, solution, concentrate". DailyMed. 7 April 2020. Archived from the original on 24 January 2021. Retrieved 16 September 2020.
- ^ a b "Gazyvaro EPAR". European Medicines Agency. 5 October 2023. Archived from the original on 2 March 2021. Retrieved 5 October 2023.
- ^ PMID 26705497.
- ^ a b "Obinutuzumab". U.S. Food and Drug Administration. 26 February 2016. Archived from the original on 27 March 2023. Retrieved 5 October 2023.
- PMID 35222385.
- PMID 37678236.
- PMID 35222385.
- S2CID 26281173.
- S2CID 20078393.
- ^ WHO Drug Information, Vol. 22, No. 2, 2008 Proposed INN: List 99 Archived 25 October 2021 at the Wayback Machine, page 123
- ^ "Roche - Roche acquires Swiss based GlycArt Biotechnology to strengthen expertise in therapeutic antibody research". roche.com. Archived from the original on 5 February 2015. Retrieved 29 April 2015.
- ^ Presentation: GlycArt Biotechnology AG From Inception to trade sale – and what happened after... by Dr. Joël Jean-Mairet. Brussels, March 31, 2011
- ^ S2CID 40983655.
- ^ "FDA approves Gazyva for chronic lymphocytic leukemia: Drug is first with breakthrough therapy designation to receive FDA approval" (Press release). FDA. 13 November 2013. Archived from the original on 21 August 2015. Retrieved 20 July 2015.
- ^ "F.D.A. Clears New Cancer-Fighting Drug From Roche". The New York Times. Associated Press. 2 November 2013. Archived from the original on 6 October 2021. Retrieved 16 September 2020.
- ^ "NICE denies Roche cancer drug due to 'data uncertainties'". PM Live. 3 October 2014. Archived from the original on 6 October 2014. Retrieved 3 October 2014.
- ^ "NICE technology appraisal guidance (TA343)". 2 June 2015. Archived from the original on 15 March 2016. Retrieved 14 March 2016.
- ^ "Final Recommendation for Obinutuzumab (Gazyva) for CLL Pan-Canadian Oncology Drug Review (pERC) Meeting: December 18, 2014; Early Conversion: pCODR" (PDF). Pan-Canadian Oncology Drug Review via Canadian Agency for Drugs and Technologies in Health. 27 January 2015. Archived (PDF) from the original on 18 October 2015. Retrieved 22 November 2015.
- ^ "FDA Approves Ibrutinib/Obinutuzumab for Treatment-Naive Patients with Chronic Lymphocytic Leukemia". Archived from the original on 4 August 2020. Retrieved 4 June 2019.
External links
- "Obinutuzumab". NCI Dictionary of Cancer Terms. National Cancer Institute.
- "Obinutuzumab". National Cancer Institute. 12 November 2013.