The Committee for Medicinal Products for Human Use ( CHMP ) of European Medicine Agency ( EMA ) has adopted a positive opinion for Gazyvaro ( Obinutuzumab; Gazyva in U.S. ) in combination with Bendamustine chemotherapy followed by Gazyvaro maintenance as a new treatment for people with follicular lymphoma who did not respond to, or who progressed during or up to six months after treatment with MabThera ( Rituximab ) or a MabThera-containing regimen.
Each year, approximately 19,000 people in Europe are diagnosed with follicular lymphoma, the most common type of indolent ( slow-growing ) non-Hodgkin lymphoma.
Follicular lymphoma is considered incurable, and most people relapse repeatedly.
The CHMP’s recommendation is based on results from the phase III GADOLIN study which showed that, in people with follicular lymphoma who did not respond to or who progressed during or within six months of prior Rituxan-based therapy, treatment with Obinutuzumab plus Bendamustine followed by Obinutuzumab alone resulted in a 52% reduction ( hazard ratio, HR=0.48, 95% CI 0.34-0.68, p less than 0.0001 ) in the risk of disease worsening or death ( progression-free survival, PFS ), compared to Bendamustine alone, as evaluated by an independent review committee ( IRC ).
The median PFS was not yet reached in those receiving the Obinutuzumab regimen, compared with 13.8 months in those receiving Bendamustine alone.
As assessed by investigator review, median progression-free survival with the Obinutuzumab regimen was more than double that with Bendamustine alone ( 29.2 months vs. 13.7 months; HR=0.48, 95% CI 0.35-0.67, p less than 0.0001 ).
Gazyvaro is already approved in the European Union ( EU ) in combination with Chlorambucil for people with previously untreated chronic lymphocytic leukaemia ( CLL ) and comorbidities that make them unsuitable for full-dose Fludarabine based therapy. That approval was based on data from the pivotal CLL11 study, where the combination of Obinutuzumab plus Chlorambucil showed superior efficacy when compared head-to-head with Rituxan plus Chlorambucil and Chlorambucil alone.
GADOLIN is a phase III open-label, multicentre, randomised two-arm study evaluating Obinutuzumab plus Bendamustine followed by Obinutuzumab alone until disease progression or for up to two years compared to Bendamustine alone.
GADOLIN included 396 patients with indolent non-Hodgkin lymphoma ( NHL ), including 321 patients with follicular lymphoma, whose disease progressed during or within six months of prior Rituxan-based therapy.
The primary endpoint of the study is progression-free survival as assessed by IRC, with secondary endpoints including progression-free survival as assessed by investigator review, best overall response ( BOR ), complete response ( CR ), partial response ( PR ), duration of response, overall survival ( OS ) and safety profile.
The Obinutuzumab regimen reduced the risk of death ( overall survival ) by 38% compared to Bendamustine alone based on a post-hoc analysis eight months after the primary analysis ( HR=0.62, 95% CI 0.39-0.98 ). The median overall survival has not yet been reached in either study arm.
The most common grade 3-4 adverse events that occurred more often ( at least 2% or greater ) in those receiving Obinutuzumab plus Bendamustine regimen compared to those receiving Bendamustine alone were low white blood cell count ( neutropenia; 33% vs 26% ), infusion-related reactions ( 11% vs 6% ) and urinary tract infection ( 3% vs 0% ), respectively.
Obinutuzumab is an engineered monoclonal antibody designed to attach to CD20, a protein found only on B-cells. Obinutuzumab destroyes targeted B-cells both directly and together with the body's immune system.
Follicular lymphoma is the most common indolent form of non-Hodgkin lymphoma, accounting for about one in five cases of NHL. It is considered incurable and relapse is common.
Every year, approximately 19,000 people in Europe are diagnosed with this type of NHL. It is estimated that each year more than 75,000 people are diagnosed with follicular lymphoma worldwide. ( Xagena )
Source: Roche, 2016