Basel, 16 May 2019 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the US Food and Drug Administration (FDA) has approved Venclexta® (venetoclax) in combination with Gazyva® (obinutuzumab) for the treatment of people with previously untreated chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL). 

"Venclexta plus Gazyva is the only chemotherapy-free option of fixed duration that provides durable responses to help people live longer without progression of their disease, compared to a standard-of-care," said Sandra Horning, MD, Roche's Chief Medical Officer and Head of Global Product Development. "Today's approval represents our long-standing commitment to helping people with blood cancers throughout the course of their disease, and we are excited to provide this new option for untreated chronic lymphocytic leukaemia."

The approval is based on the results of the randomised phase III CLL14 study, which evaluated 12-month, fixed-duration treatment with Venclexta plus Gazyva compared to Gazyva plus chlorambucil. Results showed the combination of Venclexta plus Gazyva produced a durable and significant reduction in the risk of disease worsening or death (progression-free survival [PFS], as assessed by Independent Review Committee) by 67% compared to Gazyva plus chlorambucil, a current standard-of-care (HR=0.33; 95% CI 0.22-0.51; p<0.0001). Venclexta plus Gazyva showed deep and clinically meaningful responses characterised by a higher rate of minimal residual disease (MRD)-negativity in the bone marrow compared to Gazyva plus chlorambucil (MRD-negativity of 57% vs. 17%) and peripheral blood (MRD-negativity of 76% vs. 35%). MRD-negativity means no cancer can be detected using a specific and highly sensitive test, defined as less than one CLL cell in 10,000 white blood cells. 

Results of the study will be presented at the American Society of Clinical Oncology Annual Meeting in June 2019. The CLL14 study is being conducted in cooperation with the German CLL Study Group (GCLLSG), headed by Michael Hallek, MD, University of Cologne.

The most common adverse reactions with Venclexta plus Gazyva were low white blood cell count, diarrhoea, fatigue, nausea, low red blood cell count, and upper respiratory tract infection.

The FDA rapidly reviewed and approved the supplemental New Drug Application (sNDA) under the FDA's Real-Time Oncology Review (RTOR) and Assessment Aid pilot programmes. This is the second regimen of Roche medicines approved under the RTOR pilot programme, which is exploring a more efficient review process to ensure safe and effective treatments are available to patients as early as possible. The sNDA was also granted Priority Review, a designation given 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 FDA previously granted Breakthrough Therapy Designation for Venclexta in combination with Gazyva for the treatment of previously untreated CLL with co-existing medical conditions. Additional submissions of the CLL14 data to health authorities around the world are ongoing.

Venclexta 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 plus Gazyva compared to Gazyva 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 alongside six-month duration of Gazyva (Arm A) or six-month duration of Gazyva plus chlorambucil followed by an additional six-month duration of chlorambucil (Arm B). Arm A started with an initial cycle of Gazyva followed by a five-week Venclexta dose ramp-up to help reduce tumour burden. The primary endpoint of the study is investigator-assessed progression-free survival (PFS). Secondary endpoints include PFS assessed by independent review committee (IRC), minimal residual disease (MRD) status, overall response (OR), complete response (with or without complete blood count recovery, CR/CRi), overall survival (OS), duration of response (DOR), event-free survival (EFS), time to next CLL treatment (TTNT) and safety. The CLL14 study is being conducted in cooperation with the German CLL Study Group (GCLLSG), headed by Michael Hallek, MD, University of Cologne.

Approval based on secondary endpoint of PFS evaluated by IRC; data at median follow-up of 28 months

Data at 3-months following end of combination treatment

The most common adverse reactions with Venclexta plus Gazyva were low white blood cell count, diarrhoea, fatigue, nausea, low red blood cell count, and upper respiratory tract infection.

About Venclexta/Venclyxto (venetoclax) 

Venclexta/Venclyxto is a first-in-class targeted medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumours, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta/Venclyxto blocks the BCL-2 protein and works to restore the process of apoptosis.

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, under the brand name Venclyxto, outside of the US. Together, the companies are committed to research with Venclexta/Venclyxto, which is currently being studied in clinical trials across several types of blood and other cancers.

In the US, Venclexta has been granted five Breakthrough Therapy Designations by the US Food and Drug Administration: one for previously untreated CLL, two for relapsed or refractory CLL and two for previously untreated acute myeloid leukaemia.

About Gazyva/Gazyvaro (obinutuzumab)

Gazyva/Gazyvaro is an engineered monoclonal antibody designed to attach to CD20, a protein expressed on certain B cells, but not on stem cells or plasma cells. Gazyva/Gazyvaro is designed to attack and destroy targeted B-cells both directly and together with the body's immune system. Gazyva is marketed as Gazyvaro in the EU and Switzerland.

Gazyva/Gazyvaro is currently approved in more than 90 countries in combination with chlorambucil for people with previously untreated chronic lymphocytic leukaemia, in more than 80 countries in combination with bendamustine for people with certain types of previously treated follicular lymphoma and in more than 70 countries in combination with chemotherapy for previously untreated follicular lymphoma.

Additional combination studies investigating Gazyva/Gazyvaro with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are underway across a range of blood cancers.

About the German CLL Study Group (GCLLSG)
Founded in 1996 and headed by Michael Hallek, MD, the GCLLSG has been running various phase III, phase II and phase I trials in chronic lymphocytic leukaemia (CLL) with the goal to provide optimal treatment to patients suffering from this disease. Among those were landmark trials like the CLL8 and the CLL11 trials which led to the current standard of care in CLL. For many years, GCLLSG has been aiming to improve not just the treatment of younger and physically fit patients, but also that of elderly and less fit patients. These patients are generally underrepresented in clinical trials although they constitute the majority of CLL patients treated by doctors in daily practice. The GCLLSG is an independent non-profit research organisation supported by the German Cancer Aid (Deutsche Krebshilfe) www.dcllsg.de.

About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for over 20 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera®/Rituxan® (rituximab), Gazyva®/Gazyvaro® (obinutuzumab), Venclexta®/Venclyxto® (venetoclax) in collaboration with AbbVie, and Hemlibra® (emicizumab). Our pipeline of investigational haematology medicines includes polatuzumab vedotin, an anti-CD79b antibody drug conjugate; idasanutlin, a small molecule which inhibits the interaction of MDM2 with p53; T-cell engaging bispecific antibodies targeting both CD20 and CD3, and Tecentriq® (atezolizumab), a monoclonal antibody designed to bind with PD-L1. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further. 

About Roche
Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare – a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. 
Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. Thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the tenth consecutive year, Roche has been recognised as the most sustainable company in the Pharmaceuticals Industry by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2018 employed about 94,000 people worldwide. In 2018, Roche invested CHF 11 billion in R&D and posted sales of CHF 56.8 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.