Roche, a global pioneer in pharmaceuticals and diagnostics, announced that the US Food and Drug Administration (FDA) approved Gazyva (obinutuzumab) plus bendamustine chemotherapy followed by Gazyva alone as a new treatment for people with follicular lymphoma who did not respond to a Rituxan (rituximab)-containing regimen, or had their follicular lymphoma return after such treatment. Follicular lymphoma is the most common type of indolent (slow-growing) non-Hodgkin lymphoma (NHL) and accounts for approximately one in five cases of NHL.

“People with follicular lymphoma whose disease returns or worsens despite treatment with a Rituxan-containing regimen need more options because the disease becomes more difficult to treat each time it comes back,” said Sandra Horning, MD, chief medical officer and head of global product development. “Gazyva plus bendamustine provides a new treatment option that can be used after relapse to significantly reduce the risk of progression or death.”

The approval is based on results from the phase III GADOLIN study, which showed that, in people with follicular lymphoma whose disease progressed during or within six months of prior MabThera/Rituxan-based therapy, Gazyva/Gazyvaro plus bendamustine followed by Gazyva/Gazyvaro alone demonstrated a 52 per cent reduction (HR=0.48, 95 per cent CI 0.34-0.68, p<0.0001) in the risk of disease worsening or death (progression-free survival, PFS), compared to bendamustine alone, as assessed by an independent review committee (IRC). The supplemental Biologics License Application based on these data was granted Priority Review, a designation granted to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease.

The safety of Gazyva/Gazyvaro was evaluated based on 392 people in the GADOLIN study with indolent NHL of whom 81 per cent had follicular lymphoma. The most common Grade 3-4 side effects of this Gazyva/Gazyvaro regimen were low white blood cell counts, infusion reactions and low platelet counts. The most common side effects of this Gazyva/Gazyvaro regimen were infusion reactions, low white blood cell counts, nausea, fatigue, cough, diarrhoea, constipation, fever, low platelet counts, vomiting, upper respiratory tract infection, decreased appetite, joint or muscle pain, sinus infection, low red blood cell counts, general weakness and urinary tract infection.

With this approval, Gazyva is approved in the United States to treat two common types of blood cancer. Gazyva is also approved in combination with chlorambucil for people with previously untreated chronic lymphocytic leukemia (CLL) based on data from the pivotal CLL11 study, which compared Gazyva/Gazyvaro plus chlorambucil head-to-head with MabThera/Rituxan plus chlorambucil.

Marketing applications for Gazyva/Gazyvaro based on the GADOLIN study results have also been submitted to other regulatory authorities, including the European Medicines Agency (EMA), for approval consideration.

GADOLIN (NCT01059630; GA04753g) is a phase III open-label, multicentre, randomised two-arm study evaluating Gazyva/Gazyvaro plus bendamustine followed by Gazyva/Gazyvaro alone until disease progression or for up to two years compared to bendamustine alone. GADOLIN included 413 patients with indolent (slow-growing) non-Hodgkin lymphoma (NHL), including 321 patients with follicular lymphoma, whose disease progressed during or within six months of prior MabThera/Rituxan-based therapy. The primary endpoint of the study is progression-free survival (PFS) as assessed by an independent review committee (IRC), with secondary endpoints including PFS as assessed by investigator review, best overall response (BOR), complete response (CR), partial response (PR), duration of response, overall survival (OS) and safety profile. Results in follicular lymphoma showed:

The Gazyva/Gazyvaro regimen improved PFS compared to bendamustine alone, as assessed by IRC (HR=0.48, 95 per cent CI 0.34-0.68, p<0.0001). Median PFS was not reached in those receiving the Gazyva/Gazyvaro regimen versus 13.8 months in those receiving bendamustine alone.

Investigator-assessed PFS was consistent with IRC-assessed PFS. As assessed by investigator review, median PFS with the Gazyva/Gazyvaro regimen was more than double that with bendamustine alone (29.2 months vs. 13.7 months; HR=0.48, 95 percent CI 0.35-0.67, p<0.0001).

In addition, BOR for those receiving the Gazyva/Gazyvaro regimen was 78.7 per cent (15.5 per cent CR, 63.2 percent PR) compared to 74.7 per cent for those receiving bendamustine alone (18.7 per cent CR, 56 per cent PR), as assessed by IRC.

The median duration of response was not reached for those receiving the Gazyva/Gazyvaro regimen and was 11.6 months for those receiving bendamustine alone.

The Gazyva/Gazyvaro regimen reduced the risk of death (OS) by 38 per cent compared to bendamustine alone based on a post-hoc analysis eight months after the primary analysis (HR=0.62, 95 percent CI 0.39-0.98). The median OS has not yet been reached in either study arm.

The most common Grade 3-4 adverse events that occurred more often (at least 2 per cent or greater) in those receiving the Gazyva/Gazyvaro regimen compared to those receiving bendamustine alone were low white blood cell count (33 per cent vs. 26 per cent), infusion-related reactions (11 per cent vs. 6 per cent) and urinary tract infection (3 per cent vs. 0 per cent), respectively.

Gazyva/Gazyvaro is an engineered monoclonal antibody designed to attach to CD20, a protein found only on B-cells. Gazyva/Gazyvaro is designed to attack and destroy targeted B-cells both directly and together with the body's immune system. Gazyva/Gazyvaro is currently approved in more than 60 countries in combination with chlorambucil, for people with previously untreated chronic lymphocytic leukaemia. The approval was based on the CLL11 study, showing significant improvements with Gazyva/Gazyvaro plus chlorambucil across multiple clinical endpoints, including PFS, overall response rate (ORR), complete response rate (CR), and minimal residual disease (MRD) when compared head-to-head with MabThera/Rituxan plus chlorambucil. Gazyva is marketed as Gazyvaro in the EU and Switzerland.

Gazyva/Gazyvaro is being studied in a large clinical programme, including the phase III GOYA and GALLIUM studies. GOYA is comparing Gazyva/Gazyvaro head-to-head with MabThera/Rituxan plus CHOP chemotherapy in first line diffuse large B-cell lymphoma (DLBCL) and GALLIUM is comparing Gazyva/Gazyvaro plus chemotherapy followed by Gazyva/Gazyvaro maintenance head-to-head with MabThera/Rituxan plus chemotherapy followed by MabThera/Rituxan maintenance in first line indolent non-Hodgkin lymphoma (iNHL). Additional combination studies investigating Gazyva/Gazyvaro with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are planned or underway across a range of blood cancers.