Skip to main content

Advertisement

SpringerLink
Log in

Obinutuzumab: First Global Approval

  • R&D Insight Report
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Obinutuzumab (Gazyva™) is an intravenously administered, humanized and glycoengineered, type II anti-CD20 monoclonal antibody for the treatment of B-cell malignancies. It is approved in the US for use in combination with chlorambucil for the first-line treatment of chronic lymphocytic leukaemia (CLL), and has been filed for approval in the EU in this indication. The antibody is based on GlycArt Biotechnology’s (later Roche Glycart AG) proprietary GlycoMAb® technology, which uses glycoengineered antibodies that specifically increase antibody-dependent cellular cytotoxicity and thereby increase immune-mediated target cell death. Obinutuzumab is a type II anti-CD20 antibody that induces enhanced direct cell death. The monoclonal antibody is in worldwide phase III development with Roche and its subsidiaries, Genentech and Chugai Pharmaceutical, as well as Biogen Idec, for diffuse large B-cell lymphoma and non-Hodgkin’s lymphoma generally, and is also in phase III development in countries outside of the US and EU for CLL.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Seiler TM, Hiddemann W. Advances in the management of follicular lymphoma. Curr Opin Oncol. 2012;24(6):742–7.

    Article  CAS  PubMed  Google Scholar 

  2. Goede V, Hallek M. Optimal pharmacotherapeutic management of chronic lymphocytic leukaemia: considerations in the elderly. Drugs Aging. 2011;28:163–76.

    Article  CAS  PubMed  Google Scholar 

  3. Chang JE, Kahl BS. Current status of targeted therapies for mantle cell lymphoma. Drugs. 2011;71:2307–26.

    Article  CAS  PubMed  Google Scholar 

  4. Merli M, Ferrario A, Basilico C, et al. Novel agents in indolent lymphomas. Ther Adv Hematol. 2013;4(2):133–48.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Klein C, Lammens A, Schafer W, et al. Epitope interactions of monoclonal antibodies targeting CD20 and their relationship to functional properties. mAbs. 2013;5(1):22–33.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Honeychurch J, Alduaij W, Azizyan M, et al. Antibody-induced nonapoptotic cell death in human lymphoma and leukemia cells is mediated through a novel reactive oxygen species-dependent pathway. Blood. 2012;119(15):3523–33.

    Article  CAS  PubMed  Google Scholar 

  7. US FDA. FDA approves Gazyva for chronic lymphocytic leukemia [media release]. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm373209.htm. Accessed 1 Nov 2013.

  8. US FDA. Gazyva (obinutuzumab): US prescribing information. 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125486s000lbl.pdf. Accessed 14 Nov 2013.

  9. Moritoki YB, Lian ZX, Lindor K, et al. Cell depletion with anti-CD20 ameliorates autoimmune cholangitis but exacerbates colitis in transforming growth factor-beta receptor II dominant negative mice. Hepatology. 2009;50(6):1893–903.

    Article  CAS  PubMed  Google Scholar 

  10. Chugai Pharmaceutical Co Ltd, Nippon Shinyaku Co Ltd. Co-development and co-marketing agreement for the glycoengineered type II anti-CD20 monoclonal antibody, “GA101 (obinutuzumab)” [media release]. http://www.chugai-pharm.co.jp. Accessed 27 Nov 2012.

  11. Genentech, Roche. Genentech, GlycArt and Roche enter into collaboration agreement for potential cancer therapy [media release]. http://www.gene.com. Accessed 3 Oct 2008.

  12. Biogen Idec. Biogen Idec elects to participate with Genentech in the development and commercialization of a next generation anti-CD20 molecule [media release]. http://www.biogenidec.com. Accessed 31 Oct 2008.

  13. Biogen Idec, Genentech Inc. Biogen Idec and Genentech announce restructuring of anti-CD20 collaboration agreement [media release]. http://www.gene.com. Accessed 22 Oct 2010.

  14. GlycArt Biotechnology AG. Acquisition of GlycArt Biotechnology completed [media release]. http://www.glycart.com. Accessed 26 Jul 2005.

  15. Niederfellner G, Lammens A, Mundigl O, et al. Epitope characterization and crystal structure of GA101 provide insights into the molecular basis for type I/II distinction of CD20 antibodies. Blood. 2011;118(2):358–67.

    Article  CAS  PubMed  Google Scholar 

  16. Mossner E, Brunker P, Moser S, et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood. 2010;115(22):4393–402.

    Article  CAS  PubMed  Google Scholar 

  17. Herter S, Herting F, Mundigl O, et al. Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models. Mol Cancer Ther. 2013;12(10):2031–42.

    Article  CAS  PubMed  Google Scholar 

  18. Rafiq S, Butchar JP, Cheney C, et al. Comparative assessment of clinically utilized CD20-directed antibodies in chronic lymphocytic leukemia cells reveals divergent NK cell, monocyte, and macrophage properties. J Immunol. 2013;190(6):2702–11.

    Article  CAS  PubMed  Google Scholar 

  19. Cartron G, Morschhauser F, Thieblemont C, et al. Results from a phase II study of obinutuzumab (GA101) monotherapy in relapsed/refractory chronic lymphocytic leukemia (CLL) [abstract no. 0101]. Haematologica. 2011;96(Suppl 2):39–40.

    Google Scholar 

  20. Morschhauser F, Cartron G, Lamy T, et al. Phase I study of RO5072759 (GA101) in relapsed/refractory chronic lymphocytic leukemia [abstract no. 884]. Blood. 2009;114 Suppl.

  21. Salles G, Morschhauser F, Lamy T, et al. Phase I study of RO5072759 (GA101) in patients with relapsed/refractory CD20+ non-Hodgkin lymphoma [abstract no. 1704]. Blood. 2009;114 Suppl.

  22. Sehn LH, Assouline SE, Stewart DA, et al. A phase I study of GA101 (RO5072759) monotherapy followed by maintenance in patients with multiply relapsed/refractory CD20+ malignant disease [abstract no. 934]. Blood. 2009;114 Suppl.

  23. Meneses-Lorente G, Carlile D, Birkett J, et al. Pharmacokinetics of RO5072759 (GA101) in patients with relapsed/refractory CD20+ malignant disease (phase I/II study BO20999) [abstract no. 1833]. Blood. 2010;116.

  24. Goede V, Fischer K, Busch R, et al. Head-to-head comparison of obinutuzumab (GA101) plus chlorambucil (Clb) versus rituximab plus Clb in patients with chronic lymphocytic leukemia (CLL) and co-existing medical conditions (comorbidities): final stage 2 results of the CLL11 trial. 55th American Society of Hematology Annual Meeting and Exposition, 7–10 Dec, New Orleans. 2013. https://ash.confex.com/ash/2013/webprogram/Paper60276.html.

  25. Hallek M, Fischer K, Humphrey K, et al. Obinutuzumab (GA101) + chlorambucil (CLB) or rituximab (r) + Clb versus Clb alone in patients with chronic lymphocytic leukaemia (CLL) and pre-existing medical conditions (comorbidities): final stage 1 results of the CLL11 (BO21004) phase 3 trial [abstract no. 056]. Hematol Oncol. 2013;31(Suppl 1):114–5.

    Google Scholar 

  26. Goy A, Offner F, Martinelli G, et al. Randomized phase II trial comparing obinutuzumab (GA101) with rituximab in patients with relapsed CD20+ indolent B-cell non-Hodgkin lymphoma: preliminary analysis of the GAUSS study [abstract no. 0790]. Haematologica. 2012;97(Suppl 1):322–33.

    Google Scholar 

  27. Morschhauser FA, Cartron G, Thieblemont C, et al. Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large b-cell lymphoma or mantle-cell lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013;31(23):2912–9.

    Article  CAS  PubMed  Google Scholar 

  28. Salles GA, Morschhauser F, Solal-Celigny P, et al. Obinutuzumab (GA101) in patients with relapsed/refractory indolent non-Hodgkin lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013;31(23):2920–6.

    Article  CAS  PubMed  Google Scholar 

  29. Salles G, Morschhauser F, Lamy T, et al. Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients. Blood. 2012;119(22):5126–32.

    Article  CAS  PubMed  Google Scholar 

  30. Dyer MJS, Grigg A, Gonzalez M, et al. Obinutuzumab (GA101) in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) or bendamustine in patients with previously untreated follicular lymphoma (FL): results of the phase Ib GAUDI study (BO21000) [abstract no. 3686]. Blood. 2012;120(21).

    Google Scholar 

  31. Radford J, Davies A, Cartron G, et al. Obinutuzumab (GA101) plus CHOP or FC in relapsed/refractory follicular lymphoma: results of the GAUDI study (BO21000). Blood. 2013;122(7):1137–43.

    Article  CAS  PubMed  Google Scholar 

  32. Brown JR, O’Brien S, Kingsley CD, et al. Safety and efficacy of obinutuzumab (GA101) with fludarabine/cyclophosphamide (G-FC) or bendamustine (G-B) in the initial therapy of patients with chronic lymphocytic leukemia (CLL): results from the phase 1b Galton trial (GAO4779g). 55th American Society of Hematology Annual Meeting and Exposition, 7–10 Dec, New Orleans. 2013. https://ash.confex.com/ash/2013/webprogram/Paper63449.html.

  33. Sehn LH, Assouline SE, Stewart DA, et al. A phase 1 study of obinutuzumab induction followed by 2 years of maintenance in patients with relapsed CD20-positive B-cell malignancies. Blood. 2012;119(22):5118–25.

    Article  CAS  PubMed  Google Scholar 

  34. Ogura M, Tobinai K, Hatake K, et al. Phase I study of obinutuzumab (GA101) in Japanese patients with relapsed or refractory B-cell non-Hodgkin lymphoma. Cancer Sci. 2013;104(1):105–10.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Adis R & D Insight, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, 0754, Auckland, New Zealand

    Fiona Cameron

  2. Adis, Auckland, New Zealand

    Paul L. McCormack

Authors
  1. Fiona Cameron
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul L. McCormack
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fiona Cameron.

Additional information

This profile has been extracted and modified from the Adis R&D Insight drug pipeline database. Adis R&D Insight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cameron, F., McCormack, P.L. Obinutuzumab: First Global Approval. Drugs 74, 147–154 (2014). https://doi.org/10.1007/s40265-013-0167-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-013-0167-3

Keywords

Search

Navigation