Roche announces FDA approval for Venclexta plus Rituxan for people with previously treated chronic lymphocytic leukaemia

• Approval based on phase III MURANO study showing Venclexta plus Rituxan reduced risk of disease progression or death by 81% compared to bendamustine plus Rituxan

Roche (SIX: RO, ROG; OTCQX: RHHBY), announced today that the United States Food and Drug Administration (FDA) has approved Venclexta® (venetoclax) in combination with Rituxan® (rituximab) for the treatment of people with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy. Venclexta is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the United States and commercialised by AbbVie outside of the United States.

“We are pleased that this approval makes Venclexta, a first-of-its-kind targeted therapy, available for more people with chronic lymphocytic leukaemia whose disease has returned after previous treatment,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “Venclexta plus Rituxan provides a new chemotherapy-free option shown to help people live longer without their disease progressing compared to a standard-of-care therapy.”

The approval of Venclexta plus Rituxan for people with previously treated CLL is primarily based on the results of the phase III MURANO study, which were published online in the New England Journal of Medicine in March 2018 and presented at the American Society of Hematology Annual Meeting in December 2017. The results showed that a fixed duration of treatment with Venclexta plus Rituxan significantly reduced the risk of disease progression or death (progression-free survival; PFS) by 81% compared with bendamustine plus Rituxan, a current standard of care (HR=0.19; 95% CI 0.13-0.28; p<0.0001).

The most common side effects of Venclexta in combination with Rituxan include low white blood cell count, diarrhoea,upper respiratory tract infection, cough, fatigue, and nausea.

Today’s FDA approval converts Venclexta’s accelerated approval to a full approval. The FDA has also updated the indication for Venclexta as a single agent, which is now approved for the treatment of people with CLL or SLL, with or without 17p deletion, who have received at least one prior therapy. Venclexta was previously granted accelerated approval in April 2016 as a single agent for the treatment of people with CLL with 17p deletion, as detected by an FDA approved test, who have received at least one prior therapy.

The supplemental New Drug Application based on the MURANO data was 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 also previously granted Breakthrough Therapy Designation for Venclexta in combination with Rituxan for the treatment of relapsed or refractory CLL. Venclexta in combination with Rituxan is recommended in the National Comprehensive Cancer Network guidelines as a treatment option for previously treated CLL (Category 1, Preferred).

An application for a variation of the marketing authorisation based on the MURANO data has also been submitted to and validated by the European Medicines Agency (EMA). Additional submissions of the MURANO data to health authorities around the world are ongoing.

About the MURANO study

MURANO (NCT02005471) is a phase III open-label, international, multicentre, randomised study evaluating the efficacy and safety of Venclexta in combination with Rituxan compared to bendamustine in combination with Rituxan (BR). All treatments were of fixed duration. Following a five-week dose ramp-up schedule for Venclexta, patients on the Venclexta plus Rituxan arm received six cycles of Venclexta plus Rituxan followed by Venclexta monotherapy for up to two years total. Patients on the BR arm received six cycles of BR. The study included 389 patients with chronic lymphocytic leukaemia (CLL) who had been previously treated with at least one line of therapy. Patients were randomly assigned in a 1:1 ratio to receive either Venclexta plus Rituxan or BR. The primary endpoint of the study was progression-free survival (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR) and complete response rate (with or without complete blood count recovery, CR/CRi).

At the time of analysis, median overall survival had not been reached in either arm after a median follow-up of 22.9 months.

Common Grade 3 or higher adverse reactions occurring at least 2 percent more frequently in patients treated with Venclexta plus Rituxan vs. BR, respectively, were low white blood cell count (neutropenia, 62% vs. 44%), diarrhoea (3% vs. 1%) and tumor lysis syndrome (3% vs. 1%).

About Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma

Chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia in the Western world.¹ CLL mainly affects men and the median age at diagnosis is about 70 years.² Worldwide, the incidence of all leukaemias is estimated to be over 350,000 and CLL is estimated to affect around one-third of all people newly diagnosed with leukaemia.³

In CLL, the cancer primarily occurs in the blood and bone marrow. Small lymphocytic lymphoma (SLL) is similar to CLL, but primarily occurs in the lymph nodes.

About Venclexta

Venclexta is a small molecule designed to selectively bind and inhibit the BCL-2 protein, which plays an important role in a process called apoptosis (programmed cell death). Overexpression of the BCL-2 protein in CLL has been associated with resistance to certain therapies. It is believed that blocking BCL-2 may restore the signalling system that tells cells, including cancer cells, to self-destruct. Venclexta is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the United States and commercialised by AbbVie, under the brand name Venclyxto®, outside of the United States.

Together, the companies are committed to further research with Venclexta, which is currently being evaluated in phase III clinical trials for the treatment of CLL, along with studies in several other types of cancers. In the United States, Venclexta has been granted four Breakthrough Therapy Designations by the FDA: in combination with Rituxan for people with relapsed or refractory CLL; as a monotherapy for people with relapsed or refractory CLL with 17p deletion; in combination with hypomethylating agents (azacitidine or decitabine) for people with untreated acute myeloid leukaemia (AML) ineligible for intensive chemotherapy; and in combination with low-dose cytarabine for people with untreated AML ineligible for intensive chemotherapy.

About Roche in haematology

For more than 20 years, Roche has been developing medicines that redefine treatment in haematology. Today, we are investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. In addition to approved medicines MabThera®/Rituxan® (rituximab), Gazyva®/Gazyvaro® (obinutuzumab), and Venclexta®/Venclyxto® (venetoclax) in collaboration with AbbVie, Roche’s pipeline of investigational haematology medicines includes Tecentriq® (atezolizumab), an anti-CD79b antibody drug conjugate (polatuzumab vedotin/RG7596) and a small molecule antagonist of MDM2 (idasanutlin/RG7388). Roche’s dedication to developing novel molecules in haematology expands beyond malignancy, with the development of the Hemlibra® (emicizumab), a bispecific monoclonal antibody for the treatment of haemophilia A.

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. Roche has been recognised as the Group Leader in sustainability within the Pharmaceuticals, Biotechnology & Life Sciences Industry nine years in a row by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2017 employed about 94,000 people worldwide. In 2017, Roche invested CHF 10.4 billion in R&D and posted sales of CHF 53.3 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.

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References

1. Chronic lymphocytic leukemia. Union for International Cancer Control. 2014 Review of Cancer Medicines on the WHO List of Essential Medicines [Internet; cited 2014]. Available from: http://www.who.int/selection_medicines/committees/expert/20/applications/CLL.pdf?ua=1.
2. EER Stat Fact Sheets: Chronic Lymphocytic Leukemia (CLL) [Internet; cited 2014]. Available from: http://seer.cancer.gov/statfacts/html/clyl.html.
3. Wendtner CM, et al. Chronic lymphocytic leukemia. Onkopedia guidelines 2012 [Internet; cited 2012]. Available from: https://www.onkopedia-guidelines.info/en/onkopedia/guidelines/chronic-lymphocytic-leukemia-cll/@@view/html/index.html.