|Source||Humanized (from mouse)|
|Trade names||Gazyva, Gazyvaro|
|Other names||afutuzumab, GA101|
|Elimination half-life||28.4 days|
|Chemical and physical data|
|Molar mass||146064.72 g·mol−1|
|(what is this?)|
Obinutuzumab, sold under the brand name Gazyva among others, is a humanized anti-CD20 monoclonal antibody, originated by GlycArt Biotechnology AG and developed by Roche as a cancer treatment.[medical citation needed]
It can be used as a first-line treatment for chronic lymphocytic leukemia in combination with chemotherapy or with venetoclax, as a first-line treatment for follicular lymphoma in combination with chemotherapy, and as treatment for relapsed or refractory follicular lymphoma in combination with bendamustine chemotherapy.[medical citation needed]
Obinutuzumab is used in combination with chlorambucil as a first-line treatment for chronic lymphocytic leukemia. Its progression-free survival is significantly better than rituximab in the same combination (26.7 months vs. 15.2 months, p < 0.001) but its overall survival is not significantly better (death rate 8% vs. 12%, p = .08).
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.
It was not tested in pregnant women.
In the pivotal clinical trial of obinutuzumab in combination with chlorambucil, clinical trial subjects 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.
GlycArt's technology platform allowed control of protein glycosylation; the cells in which obinutuzumab is produced were engineered to overexpress two glycosylation enzymes, MGAT3 and Golgi mannosidase 2, which reduce the amount of fucose attached to the antibody, which in turn increases the antibody's ability to activate natural killer cells.
Details of the antibody's structure are disclosed in the 2008 WHO INN naming proposal.
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.
Roche developed the drug in the US through its US subsidiary, Genentech, and in Japan through its Japanese subsidiary, Chugai. Genentech partnered with Biogen Idec to explore the use of the drug for primary biliary cirrhosis but as of 2014 it appeared the development in that indication had halted.
On November 13, 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.
In October 2014, NICE announced that NHS England would not fund use of the drug, due to data uncertainties in Roche's application. In June 2015, NICE announced that it would fund restricted use of the drug.
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 Canadian Agency for Drugs and Technologies in Health, the list price of obinutuzumab provided by the manufacturer Hoffmann-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."
In February 2016, obinutuzumab was approved by the FDA under the Priority Review program for use in combination with bendamustine followed by obinutuzumab monotherapy for the treatment of patients with follicular lymphoma as a secondline treatment to a regimen containing rituximab.
In January 2019, the US Food and Drug Administration (FDA) approved ibrutinib in combination with obinutuzumab for people with chronic lymphocytic leukemia/small lymphocytic lymphoma who have not received prior treatment.
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. It was called GA101 during research.
- WHO Drug Information, Vol. 23, No. 2, 2009 Proposed INN: List 101, p 176
- https://www.guildlink.com.au/gc/ws/ro/pi.cfm?product=ropgazyv10515[bare URL]
- "Prescription medicines: registration of new chemical entities in Australia, 2014". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
- "Gazyva- obinutuzumab injection, solution, concentrate". DailyMed. 7 April 2020. Retrieved 16 September 2020.
- Evans SS, Clemmons AB (2015). "Obinutuzumab: A Novel Anti-CD20 Monoclonal Antibody for Chronic Lymphocytic Leukemia". Journal of the Advanced Practitioner in Oncology. 6 (4): 370–4. doi:10.6004/jadpro.2015.6.4.7. PMC 4677809. PMID 26705497.
- FDA, Feb 26, 2016 Press Release: Obinutuzumab
- Ratner M (January 2014). "Genentech's glyco-engineered antibody to succeed Rituxan". Nature Biotechnology. 32 (1): 6–7. doi:10.1038/nbt0114-6b. PMID 24406911. S2CID 26281173.
- Umaña P, Jean-Mairet J, Moudry R, Amstutz H, Bailey JE (February 1999). "Engineered glycoforms of an antineuroblastoma IgG1 with optimized antibody-dependent cellular cytotoxic activity". Nature Biotechnology. 17 (2): 176–80. doi:10.1038/6179. PMID 10052355. S2CID 20078393.
- WHO Drug Information, Vol. 22, No. 2, 2008 Proposed INN: List 99, page 123
- "Roche - Roche acquires Swiss based GlycArt Biotechnology to strengthen expertise in therapeutic antibody research". roche.com. Archived from the original on 2015-02-05. Retrieved 2015-04-29.
- Presentation: GlycArt Biotechnology AG From Inception to trade sale – and what happened after... by Dr. Joël Jean-Mairet. Brussels, March 31, 2011
- Cameron F, McCormack PL (January 2014). "Obinutuzumab: first global approval". Drugs. 74 (1): 147–54. doi:10.1007/s40265-013-0167-3. PMID 24338113. S2CID 40983655.
- "FDA approves Gazyva for chronic lymphocytic leukemia: Drug is first with breakthrough therapy designation to receive FDA approval" (Press release). FDA. November 13, 2013. Retrieved July 20, 2015.
- "F.D.A. Clears New Cancer-Fighting Drug From Roche". The New York Times. Associated Press. 2 November 2013. Retrieved 16 September 2020.
- "NICE denies Roche cancer drug due to 'data uncertainties'". PM Live. 3 October 2014. Retrieved 3 October 2014.
- "NICE technology appraisal guidance (TA343)". 2 June 2015. 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. Retrieved 22 November 2015.
- "FDA Approves Ibrutinib/Obinutuzumab for Treatment-Naive Patients with Chronic Lymphocytic Leukemia". Retrieved 4 June 2019.