Obinutuzumab: First Global Approval

  title={Obinutuzumab: First Global Approval},
  author={Fiona Cameron and Paul L. McCormack},
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… 

Obinutuzumab: a novel anti-CD20 monoclonal antibody for previously untreated chronic lymphocytic leukemia.

  • Arpita Shah
  • Medicine, Biology
    The Annals of pharmacotherapy
  • 2014
Obinutuzumab in combination with chlorambucil is a safe and effective new treatment option for previously untreated elderly CLL patients and should become the new preferred therapy for patients with significant comorbidities who are not candidates for fludarabine-based therapy.

Idelalisib: First Global Approval

The milestones in the development of Idelalisib leading to this first approval for relapsed CLL, NHL and SLL are summarized.

Antibody therapy alone and in combination with targeted drugs in chronic lymphocytic leukemia.

Combinations of antibodies with targeted drugs like ibrutinib, idelalisib, or lenalidomide are expected to replace chemotherapy-based combinations for treating CLL in the near future, however, phase III trials should confirm the benefit of these new treatment strategies and establish their exact place in the therapeutic armamentarium for CLL.

Glycoengineered antibodies: towards the next-generation of immunotherapeutics

Recent innovative developments in chemo-enzymatic glycoengineering, which allow generating mAbs carrying single, well-defined, uniform Fc glycoforms, which confers the desired biological properties for the target application, are reviewed.

Current and emerging monoclonal antibody treatments for chronic lymphocytic leukemia: state of the art

  • T. Robak
  • Biology
    Expert review of hematology
  • 2014
A critical overview of established mAbs as well as new antibodies potentially useful in CLL is given to replace chemotherapy-based combinations in the near future.

Approval for Novel Drugs in Chronic Lymphocytic Leukemia

Cytotoxic agents, including chlorambucil, bendamustin and purine analogs, currently constitute the basis of the most frequently used therapeutic regimens in this leukemia, and anti- CD20 monoclonal antibodies (mAbs), rituximab and ofatumumab, and the anti-CD52 antibody alemtuzumab are included for therapeutic options.

Emerging immunological drugs for chronic lymphocytic leukemia

The use of mAbs, BCR inhibitors and immunomodulating drugs is a promising new strategy for chemotherapy-free treatment of CLL, however, definitive data from ongoing and future clinical trials will aid in better defining the status of immunological drugs in the treatment of this disease.

Novel drugs for chronic lymphocytic leukemia in 2014

It is demonstrated that ofatumumab monotherapy shows promising efficacy in heavily pretreated patients with fludarabine-and alemtuzumab-refractory CLL and is superior to chlorambucil alone in this patient population.



Preclinical Activity of the Type II CD20 Antibody GA101 (Obinutuzumab) Compared with Rituximab and Ofatumumab In Vitro and in Xenograft Models

We report the first preclinical in vitro and in vivo comparison of GA101 (obinutuzumab), a novel glycoengineered type II CD20 monoclonal antibody, with rituximab and ofatumumab, the two currently

Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients.

GA101 was well tolerated and demonstrated encouraging activity in patients with previously treated NHL up to doses of 2000 mg and the best overall response was 43%, with 5 complete responses and 4 partial responses.

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)

GALTON is a non-randomized, parallel group, phase 1b study of the safety and preliminary efficacy of GA101 plus FC or B in the initial therapy of patients with CLL, to evaluate safety and tolerability of GA 101 with chemotherapy.

Phase I study of obinutuzumab (GA101) in Japanese patients with relapsed or refractory B‐cell non‐Hodgkin lymphoma

This phase I study demonstrated that GA101 has an acceptable safety profile and offers encouraging activity to Japanese patients with relapsed/refractory B‐cell non‐Hodgkin lymphoma.

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)

The safety, toxicity, and efficacy of remission induction of GA101 in combination with CHOP or bendamustine in 81 patients aged > 18 years with treatment-naive CD20+ grade 1–3b FL with at least one measurable lesion are described.

Phase I Study of RO5072759 (GA101) in Relapsed/Refractory Chronic Lymphocytic Leukemia.

GA101 was well tolerated with no DLTs and no dose reductions, and pharmacokinetics were characterized by one linear and one time-dependent saturable clearance components, consistent with target-mediated disposition.

Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large b-cell lymphoma or mantle-cell lymphoma: results from the phase II GAUGUIN study.

Obinutuzumab 1,600/800 mg achieves early steady-state concentration and clinical activity with an acceptable safety profile in relapsed/refractory DLBCL and MCL, supporting further exploration.

Pharmacokinetics of RO5072759 (GA101) In Patients with Relapsed/Refractory CD20+ Malignant Disease (Phase I/II Study BO20999)

Results of analyses exploring GA101 exposure and response in indolent NHL patients indicate that responding patients appear to eliminate GA101 slower compared to non-responding patients.

A phase 1 study of obinutuzumab induction followed by 2 years of maintenance in patients with relapsed CD20-positive B-cell malignancies.

Odinutuzumab induction and maintenance therapy was well tolerated with promising efficacy in this heterogeneous, highly pretreated population and warrants further investigation.

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.

In human lymphoma xenograft models, GA101 exhibits superior antitumor activity, resulting in the induction of complete tumor remission and increased overall survival and in nonhuman primates, GA 101 demonstrates superior B cell-depleting activity in lymphoid tissue, including in lymph nodes and spleen.