The European Commission has approved Roche's Gazyvaro (obinutuzumab) in combination with chlorambucil chemotherapy for the treatment of people with previously untreated chronic lymphocytic leukaemia who have comorbidities making them unsuitable for an intensive therapy (full-dose fludarabine based therapy). Outside of the EU and Switzerland, Gazyvaro is marketed as Gazyva.

“We are proud to make Gazyvaro available for CLL patients in Europe,” said Sandra Horning, M.D., Roche’s chief medical officer and head, global product development. “Gazyvaro is a new option that helps patients achieve deep responses to treatment that translate to longer lasting remissions.”

The European approval was based on the outcomes of the CLL11 study which was conducted in close collaboration with the German CLL Study Group. The study showed that Gazyvaro plus chlorambucil met its primary endpoint by significantly reducing the risk of disease worsening or death by 61 per cent compared to MabThera/Rituxan plus chlorambucil (progression free survival; PFS). For patients in the Gazyvaro arm, median PFS was 26.7 months compared with 15.2 months for those in the MabThera/Rituxan arm (HR 0.39, CI 0.31-0.49, p<0.001).

Additional Gazyvaro data from the CLL11 study showed higher complete response rates (21% compared with 7%) and a ten-fold increase in the percentage of people achieving minimal residual disease (MRD) negativity (37.7% compared with 3.3%) compared to the MabThera/Rituxan arm of the study.

Gazyvaro plus chlorambucil also increased the time people with previously untreated CLL lived (overall survival, OS) compared to those who received treatment with chlorambucil alone. The most common serious adverse events (AEs) for Gazyvaro were infusion-related reactions (IRRs), infections and low cell count of certain white blood cells (neutropenia). The incidence and severity of IRRs decreased dramatically after the first infusion and no serious IRRs have been reported beyond the first infusion. These data from the CLL11 study were published in the New England Journal of Medicine.

For CLL patients in Europe, Roche expects to begin launching Gazyvaro in a number of European countries in 2014. Roche is also studying Gazyvaro in other cancers of the blood where anti-CD20 antibodies have been shown to be effective, and where future combination therapies may reduce or eliminate the need for chemotherapy.

CLL is the most common leukemia in Europe, representing 25-30% of all forms of leukemia. Each year it is responsible for approximately 20,000 new cases and 13,000 deaths across Europe.

Outside of the EU and Switzerland, Gazyvaro is marketed as Gazyva. Gazyvaro is a new, type II, glycoengineered monoclonal antibody designed to attach to CD20, a protein found only on B cells. It attacks targeted cells both directly and together with the body's immune system.

Gazyvaro was discovered by Roche Glycart AG, a part of the company's Pharma Research and Early Development organization. In November 2013, Gazyva became the first medicine with Breakthrough Therapy Designation approved by the FDA. It was approved in combination with chlorambucil for people with previously untreated chronic lymphocytic leukaemia. Globally, Gazyvaro is also being investigated in a large clinical program, including multiple head-to-head phase III studies compared to MabThera/Rituxan in indolent non-Hodgkin lymphoma (NHL) and diffuse large B-cell lymphoma (DLBCL). Additional combination studies with small molecule biologic modifiers are planned or underway across a range of blood cancers.

CLL11 is a phase III, multicentre, open-label, randomised three-arm study conducted in close collaboration with the German CLL Study Group which is investigating the efficacy and safety profile of Gazyvaro plus chlorambucil, MabThera/Rituxan plus chlorambucil and chlorambucil alone in 781 previously untreated people with CLL and co-existing medical conditions who are in need of therapy. Stage 1 (n=589) compared Gazyvaro plus chlorambucil to chlorambucil alone and MabThera/Rituxan plus chlorambucil to chlorambucil alone. Stage 2 (n=663) compared Gazyvaro plus chlorambucil directly with MabThera/Rituxan plus chlorambucil.

The primary endpoint of the study was PFS with secondary endpoints including overall response rate (ORR), overall survival (OS), disease free survival (DFS), MRD and safety profile.

For more than 20 years, Roche has been developing medicines that redefine treatment in haematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with cancers of the blood.

In addition to MabThera and Gazyvaro, Roche’s pipeline of potential haematology medicines includes an anti-CD79b antibody drug conjugate (RG7596/polatuzumab vedotin), a small molecule antagonist of MDM2 (RG7112) and in collaboration with AbbVie, a small molecule BCL-2 inhibitor (RG7601/GDC-0199/ABT-199).