New data demonstrate the continued clinical benefit of fixed-duration, chemotherapy-free Venclexta/Venclyxto-based treatments in chronic lymphocytic leukaemia

In an updated analysis of the CLL14 study, Venclexta/Venclyxto plus Gazyva/Gazyvaro achieved remissions that were sustained over time in people with previously untreated chronic lymphocytic leukaemiaAt four-year follow-up of the MURANO study, Venclexta/Venclyxto plus MabThera/Rituxan continued to reduce disease progression compared to a standard-of-care therapy in previously treated chronic lymphocytic leukaemiaData presented on both studies include results on minimal residual disease, which is currently emerging as a potential surrogate endpoint             
Basel, 8 December 2019 – Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced updated data from two pivotal phase III Venclexta®/Venclyxto® (venetoclax) studies (MURANO and CLL14) that highlight Venclexta/Venclyxto combination treatments as chemotherapy-free, fixed-duration options that achieve minimal residual disease (MRD)-negativity, in people with chronic lymphocytic leukaemia (CLL). These data and others from the Venclexta/Venclyxto clinical development programme will be featured in more than 50 abstracts at the 61st American Society of Hematology (ASH) Annual Meeting.Higher rates of MRD-negativity in peripheral blood (76% vs. 35%; p<0.001) and bone marrow (57% vs. 17; p<0.001%) were observed at the end of treatment in people treated with Venclexta/Venclyxto plus Gazyva/Gazyvaro versus Gazyva/Gazyvaro plus chlorambucil, respectively. MRD-negativity indicates that no cancer can be detected using a specific, highly sensitive test, and was defined as less than one CLL cell in 10,000 white blood cells.MRD-negativity was observed in 42 % of people treated with Venclexta/Venclyxto plus Gazyva/Gazyvaro who achieved a complete response (CR) in the peripheral blood, and 14% of people treated with Gazyva/Gazyvaro plus chlorambucil (p<0.001). In bone marrow, MRD-negativity was observed in 34% of people who achieved a complete response with Venclexta/Venclyxto plus Gazyva/Gazyvaro and 11% of people treated with Gazyva/Gazyvaro plus chlorambucil (p<0.001).At this updated analysis, the fixed-duration, chemotherapy-free combination of Venclexta/Venclyxto plus Gazyva/Gazyvaro reduced the risk of disease worsening or death by 69% compared to Gazyva/Gazyvaro plus chlorambucil (PFS, as assessed by investigator; HR=0.31; 95% CI 0.22-0.44; p<0.0001).The most common Grade 3-4 adverse events (AEs) in people treated with Venclexta/Venclyxto plus Gazyva/Gazyvaro were blood and lymphatic system disorders, and infections.These data were presented on Saturday, December 7, 2019 at 08:45 ET in an oral session (Abstract #36).
The pivotal phase III MURANO study evaluated the combination of Venclexta/Venclyxto plus MabThera®/Rituxan® (rituximab) in relapsed or refractory (R/R) CLL. Four-year, follow-up data from the study showed sustained OS and PFS benefits with Venclexta/Venclyxto plus MabThera/Rituxan compared to bendamustine plus MabThera/Rituxan (BR). No new safety events were reported in the study. Specifically:Results showed that Venclexta/Venclyxto plus MabThera/Rituxan significantly reduced the risk of disease progression or death by 81% (HR=0.19; 95% CI: 0.14, 0.25; p<0.0001) compared to BR, with four-year PFS estimates of 57.3% (95 % CI: 49.4, 65.3) vs. 4.6% (95% CI: 0.1, 9.2), respectively.Venclexta/Venclyxto plus MabThera/Rituxan also reduced the risk of death by 59% (HR=0.41; 95% CI: 0.26, 0.65; p<0.0001), compared to BR, with the Venclexta/Venclyxto plus MabThera/Rituxan treatment arm demonstrating greater sustained OS compared to the BR arm, with four-year OS rates of 85.3% vs. 66.8%, respectively.Venclexta/Venclyxto plus MabThera/Rituxan showed that people who achieved MRD-negativity showed an improvement in PFS at the end of treatment.No new safety signals were identified with the combination in this extended follow-up. Common grade 3-4 adverse events with Venclexta/Venclyxto plus MabThera/Rituxan compared to BR, respectively, were low white blood cell count (58.8% vs. 39.9%), anaemia (11.3% vs 13.8%) and low platelet count (5.7% vs 10.1%).Results from the MURANO study were the basis of regulatory approvals for Venclexta/Venclyxto plus MabThera/Rituxan as a treatment option for people with R/R CLL around the world.These data will be presented in an oral session on Sunday, December 8, 2019 at 07:30 ET (Abstract #355).
Venclexta/Venclyxto is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the US and commercialised by AbbVie outside of the US.

About the CLL14 study
CLL14 (NCT02242942) is a randomised phase III study evaluating the combination of fixed-duration Venclexta/Venclyxto (venetoclax) plus Gazyva/Gazyvaro (obinutuzumab) compared to Gazyva/Gazyvaro plus chlorambucil in patients with previously untreated chronic lymphocytic leukaemia (CLL) and co-existing medical conditions. 432 patients with previously untreated CLL were randomly assigned to receive either a 12-month duration of Venclexta/Venclyxto alongside six-month duration of Gazyva/Gazyvaro (Arm A) or six-month duration of Gazyva/Gazyvaro alongside 12-month duration of chlorambucil (Arm B). Arm A started with an initial dosing of Gazyva/Gazyvaro followed by a five-week Venclexta/Venclyxto dose ramp-up to help reduce the risk of tumour burden. The primary endpoint of the study is investigator-assessed progression-free survival (PFS). Secondary endpoints include PFS assessed by independent review committee, minimal residual disease status, overall response rate, complete response (with or without complete blood count recovery), overall survival, duration of response, event-free survival, time to next CLL treatment, and safety. The CLL14 study is being conducted in cooperation with the German CLL Study Group, headed by Michael Hallek, MD, University of Cologne.Attachment08122019_MR_ASH Venclexta_EN