Pivotal Phase II study of investigational medicine venetoclax met primary endpoint in a hard-to-treat type of chronic lymphocytic leukemia

Basel, 12 August 2015

Pivotal Phase II study of investigational medicine venetoclax met primary endpoint in a hard-to-treat type of chronic lymphocytic leukemia

  • Regulatory applications for venetoclax are planned for submission to the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) by the end of 2015
  • Venetoclax is a small molecule inhibitor of the BCL-2 protein, which potentially represents a new way of treating blood cancers

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced positive results today from the Phase II M13-982 study of venetoclax, an investigational medicine being developed in partnership with AbbVie. The study met its primary endpoint, showing that venetoclax monotherapy resulted in a clinically meaningful reduction in the number of cancer cells (overall response rate, ORR) in a pre-defined proportion of people with previously treated (relapsed or refractory) chronic lymphocytic leukemia (CLL) harboring the 17p deletion. No unexpected safety signals were reported for venetoclax.

"Approximately 30 to 50 percent of people with relapsed or refractory chronic lymphocytic leukemia have the 17p deletion that makes their disease difficult to treat," said Sandra Horning, MD, Roche's Chief Medical Officer and Head of Global Product Development. "Venetoclax may help restore the natural process that allows these leukemic cells to self destruct, representing a potential new way of helping people with this form of CLL who typically have a poor prognosis and limited treatment options."

Venetoclax was recently granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) for the treatment of previously treated CLL with the 17p deletion. This designation is designed to expedite the development and review of medicines intended to treat serious diseases. People with this type of CLL typically have a median life expectancy of less than three years.1 This is the eighth BTD granted for a Roche medicine, and the second one in hematology.

Data from the pivotal M13-982 study will be submitted for presentation at an upcoming medical meeting. AbbVie plans to submit these data to the FDA, European Medicines Agency (EMA) and other health authorities around the world for approval consideration.

About Study M13-982

M13-982 (NCT01889186) is a Phase II, open label, single arm, multicenter study evaluating the efficacy and safety of venetoclax in people with relapsed or refractory CLL harboring the 17p deletion. The main study cohort included 107 patients and approximately 50 patients will be enrolled in the safety expansion cohort. The primary endpoint of the study is overall response rate (ORR) as determined by an independent review committee, and secondary endpoints include complete response (CR), partial response (PR) and progression free survival (PFS).

About Chronic Lymphocytic Leukemia (CLL)

CLL is a slow-growing cancer of the blood and bone marrow that is generally considered incurable and is one of the most common adult leukemias worldwide.2,3 Most cases of CLL (95 percent) start in white blood cells called B-cells.2 In certain cases of CLL, a part of chromosome 17 is lost and along with it an important gene that controls apoptosis called p53.4 The 17p deletion is found in 3 to 10 percent of previously untreated cases and approximately 30 to 50 percent of relapsed or refractory cases.5 People with 17p deletion CLL have poor results with conventional chemotherapy regimens and a median life expectancy of less than three years.1

About Venetoclax (RG7601, GDC-0199/ABT-199)

Venetoclax is an investigational 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). It is believed that blocking BCL-2 may restore the signaling system that tells cancer cells to self-destruct. The BCL-2 protein is linked to the development of resistance in certain blood cancers and is expressed in chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL). In collaboration with AbbVie, venetoclax is being evaluated in a robust development program as a single agent or in combination with other medicines. There are ongoing Phase II and III studies for venetoclax in CLL, and Phase I and II studies are also ongoing in several other blood cancers, including indolent NHL, diffuse large B-cell lymphoma (DLBCL), acute myeloid leukemia (AML) and multiple myeloma (MM).

About Roche in haematology

For more than 20 years, Roche has been developing medicines with a goal of redefining treatment in hematology. Today, we're 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) and Gazyvaro/Gazyva (obinutuzumab), Roche's pipeline of investigational hematology medicines includes an anti-CD79b antibody drug conjugate (RG7596/polatuzumab vedotin), a small molecule antagonist of MDM2 (RG7112) and, in collaboration with AbbVie, a small molecule Bcl-2 inhibitor (venetoclax, RG7601/GDC-0199/ABT-199). Roche's dedication to developing novel molecules in hematology expands beyond oncology, with the development of the investigational hemophilia A treatment ACE910.

About Roche

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world's largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and neuroscience. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. Roche's personalised healthcare strategy aims at providing medicines and diagnostics that enable tangible improvements in the health, quality of life and survival of patients. Founded in 1896, Roche has been making important contributions to global health for more than a century. Twenty-nine medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and chemotherapy.

In 2014, the Roche Group employed 88,500 people worldwide, invested 8.9 billion Swiss francs in R&D and posted sales of 47.5 billion Swiss francs. 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 roche.com.

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1. Stilgenbauer, S, and Zenz, T, (2010) "Understanding and Managing Ultra High-Risk Chronic Lymphocytic Leukemia." ASH Education Book. 2010(1):481-488.
2. Leukemia & Lymphoma Society, "Chronic Lymphocytic Leukemia." http://www.lls.org/sites/default/files/file_assets/cll.pdf
3. Leukemia & Lymphoma Society, "Chronic Lymphocytic Leukemia." http://www.lls.org/leukemia/chronic-lymphocytic-leukemia
4. Selner, L. et al. (2013) "What Do We Do with Chronic Lymphocytic Leukemia with 17p Deletion?" Curr Hemetol Malig Rep. 8(1):81-90.
5. Schnaiter, A. et al. (2013) "17p Deletion in Chronic Lymphocytic Leukemia: Risk Stratification and Therapeutic Approach." Hematol Oncol Clin N Am 27 (2013) 289–301