Products

* On December 24, 2014, Genentech, a member of the Roche Group, announced that the FDA approved a supplemental biologics license application (sBLA) for Gazyva® in combination with chlorambucil chemotherapy in people with previously untreated chronic lymphocytic leukemia (CLL). The sBLA adds to the label data from Stage 2 of the CLL11 study showing significant improvements with Gazyva in combination with chlorambucil chemotherapy plus chlorambucil across multiple clinical endpoints when compared head-to-head with Rituxan® (rituximab) plus chlorambucil. The approval includes complete response (CR) and minimal residual disease (MRD) data from Stage 2 of the study. Additionally, overall survival (OS) data was added from Stage 1 of the study comparing Gazyva® plus chlorambucil to chlorambucil alone. The sBLA approval updated the Gazyva prescribing information with the following data: Gazyva® plus chlorambucil helped people with previously untreated CLL live nearly a year longer without their disease worsening or death (progression-free survival; PFS) than Rituxan plus chlorambucil (median PFS: 26.7 months vs. 14.9 months, respectively. HR=0.42, 95 percent CI 0.33-0.54, p<0.0001). Gazyva® plus chlorambucil nearly tripled the number of people showing no evidence of disease (CR) compared to Rituxan plus chlorambucil (26.1 percent vs. 8.8 percent, respectively).

Of the people who achieved a complete response with or without complete recovery from abnormal blood cell counts (CR, CRi), 19 percent (18/94) of people in the Gazyva® arm compared to 6 percent (2/34) of people in the Rituxan® arm were MRD negative in the bone marrow, and 41 percent (39/94) of people in the Gazyva arm compared to 12 percent (4/34) people in the Rituxan arm were MRD negative in the peripheral blood. MRD negative means no residual traces of the cancer were found.
Data from the first stage of the CLL11 study showed that at nearly two years, the rate of death was 9 percent (22/238) for people who received Gazyva plus chlorambucil compared to 20 percent (24/118) for those who received chlorambucil alone (HR=0.41, 95 percent CI 0.23-0.74). The median OS has not yet been reached.
Gazyva® can cause serious or life-threatening side effects including: Hepatitis B reactivation, progressive multifocal leukoencephalopathy (PML), infusion reactions, tumor lysis syndrome, infections, and low white blood cell counts. The most common side effects of Gazyva are infusion reactions, low white blood cell counts, low platelet counts, low red blood cell counts, fever, cough, nausea, and diarrhea.
Gazyva®, the first medicine approved with the FDA’s Breakthrough Therapy Designation, was approved for use in combination with chlorambucil in people with previously untreated CLL on November 1, 2013. Gazyva®, known as Gazyvaro® in Europe, was approved by the European Commission for the same indication in July 2014. Gazyva® is also being investigated in a broad development program across various types of blood cancers, including multiple Phase III studies in non-Hodgkin’s lymphoma (NHL).

* On July 29, 2014 , Roche announced that the European Commission has approved Gazyvaro® (obinutuzumab) in combination with chlorambucil chemotherapy for the treatment of people with previously untreated chronic lymphocytic leukemia who have comorbidities making them unsuitable for an intensive therapy (full-dose fludarabine based therapy).  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% 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.1
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.

*On 22 May 2014, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Gazyvaro® 1,000 mg concentrate for solution for infusion intended for the treatment in combination with chlorambucil of adult patients with previously untreated chronic lymphocytic leukaemia (CLL) and with comorbidities making them unsuitable for full-dose fludarabine based therapy. Gazyvaro® was designated as an orphan medicinal product on 10 October 2012. The benefits with Gazyvaro® used in combination with chlorambucil (Clb) are its ability to delay the progression of disease compared to Clb alone or rituximab in combination with Clb. The most common side effects are infusion-related reactions (IRRs) which occurred in the majority of patients during the first cycle, neutropenia and infections. A pharmacovigilance plan will be implemented as part of the marketing authorisation.

* On November 1, 2013, the FDA has approved Gazyva®for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia (CLL). Gazyva® works by helping certain cells in the immune system attack cancer cells. Gazyva® is the first drug with breakthrough therapy designation to receive FDA approval. This designation was requested by the sponsor and granted soon after the biologic license application to support marketing approval was submitted to the FDA. The FDA can designate a drug a breakthrough therapy at the request of the sponsor if preliminary clinical evidence indicates the drug may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases.

The FDA also granted Gazyva® priority review because the drug demonstrated the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. And the FDA granted Gazyva® orphan product designation because it is intended to treat a rare disease.

Gazyva®’s approval for CLL is based on a study of 356 participants in a randomized open-label multicenter trial comparing Gazyva in combination with chlorambucil to chlorambucil alone in participants with previously untreated CLL. Participants receiving Gazyva in combination with chlorambucil demonstrated a significant improvement in progression free survival: an average of 23 months compared with 11.1 months with chlorambucil alone.

The most common side effects observed in participants receiving Gazyva in combination with chlorambucil were infusion-related reactions, a decrease in infection-fighting white blood cells (neutropenia), a low level of platelets in the blood (thrombocytopenia), low red blood cells (anemia), pain in the muscles and bones (musculoskeletal pain), and fever (pyrexia).

Gazyva® is being approved with a boxed warning regarding Hepatitis B virus reactivation and a rare disorder that damages the material that covers and protects nerves in the white matter of the brain (progressive multifocal leukoencephalopathy). These are known risks with other monoclonal antibodies in this class and rare cases were identified in participants on other trials of Gazyva®. Patients should be advised of these risks and assessed for Hepatitis B virus and reactivation risk.

* On July 2, 2013,  Genentech, a member of the Roche Group, has announced that the FDA has accepted the company's Biologics License Application (BLA) for obinutuzumab (GA101) and granted Priority Review for GA101 in the treatment of chronic lymphocytic leukemia (CLL), based on final Stage 1 data from the pivotal CLL11 trial. The FDA confirmed the action date is December 20, 2013. This acceptance follows the GA101 FDA Breakthrough Therapy Designation that was received in May 2013.

The FDA is evaluating data from the pivotal Phase III CLL11 trial, which found that GA101 demonstrated a statistically significant 86 percent reduction in the risk of disease worsening or death (HR=0.14, 95 percent CI 0.09-0.21, p<0.0001) when combined with chlorambucil chemotherapy compared to chlorambucil alone in previously untreated people with CLL and co-existing medical conditions. In CLL11, no new safety signals were detected for GA101. The most common Grade 3-4 adverse events (AEs) for GA101 were infusion-related reactions (IRRs) and low cell count of certain white blood cells (neutropenia) which did not result in an increased risk of infection. The incidence and severity of IRRs decreased after the first infusion and no Grade 3-4 IRRs have been reported beyond the first infusion. Marketing applications have also been submitted to other regulatory authorities, including the European Medicines Association (EMA), in April 2013. In the United States, Genentech has opened an Expanded Access Program (EAP) to provide GA101 to people with CLL under certain circumstances while the company seeks regulatory approval.

* On May 22, 2013, the COMP has announced that obinutuzumab has been subject of a new EU marketing authorization application under the centralised procedure.

* On September 4, 2012, the COMP has adopted a positive opinion recommending obinutuzumab for designation as orphan medicinal products for the treatment of chronic lymphocytic leukaemia.