Sunday, Dec 6, 2015

Pivotal Phase II Study Showed Nearly 80 Percent of People with Hard-to-treat Type of Chronic Lymphocytic Leukemia Responded to Investigational Medicine Venetoclax

  • Regulatory applications for venetoclax have been submitted to the U.S. Food and Drug Administration and European Medicines Agency
  • Additional results in previously treated chronic lymphocytic leukemia from a separate Phase Ib study published online today in New England Journal of Medicine

South San Francisco, CA -- December 6, 2015 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced new, positive data from the Phase II M13-982 study of venetoclax, an investigational medicine being developed in partnership with AbbVie. Results of the study showed a clinically meaningful reduction in the number of cancer cells (overall response rate, ORR) in 79.4 percent of people with previously treated (relapsed or refractory) chronic lymphocytic leukemia (CLL) with 17p deletion. No unexpected safety signals were reported for venetoclax.

“The high response rates, including complete responses and duration of response, demonstrate the potential of venetoclax to help people with this hard-to-treat type of leukemia,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “This is a patient population that has very few treatment options, and we are working with AbbVie to bring this new option to people as quickly as possible.”

These pivotal data from the Phase II M13-982 study were featured in the official press program of the 57th American Society of Hematology (ASH) Annual Meeting in Orlando on Sunday, December 6, and will be presented during the Late-Breaking Abstracts Session on Tuesday, December 8, at 7:30 A.M. EST by Dr. Stephan Stilgenbauer, University of Ulm, Germany (Abstract #LBA6). The results show:

· The study met its primary endpoint, with an ORR of 79.4 percent with venetoclax, as assessed by an independent review committee (IRC). In addition, 7.5 percent of people achieved a complete response with or without complete recovery (complete response without normal blood counts) in the bone marrow (CR/CRi).

· Forty-five people had an assessment for minimal residual disease (MRD) in the blood. Notably 18 people (17 percent of the total, 21 percent of responders) achieved MRD-negativity, meaning no cancer could be detected using a specific test. Ten of these 18 people also had bone marrow assessments and six were MRD-negative.

· At one year, 84.7 percent of all responses and 94.4 percent of MRD-negative responses were maintained. The one-year progression-free survival (PFS) and overall survival (OS) rates were 72 percent and 86.7 percent, respectively.

· No unexpected safety signals were reported. The most common Grade 3-4 adverse events were low white blood cell count (40 percent), low red blood cell count (18 percent), and low platelet count (15 percent). Grade 3 or higher infection occurred in 20 percent of people. Laboratory tumor lysis syndrome was reported in five people; none had clinical consequences.

Data for venetoclax as a monotherapy or in combinations with other medicines across multiple blood cancers, including CLL, non-Hodgkin’s lymphoma (NHL), multiple myeloma (MM) and acute myeloid leukemia (AML), will also be presented during the ASH Annual Meeting.

Separately, positive results in people with CLL included in the Phase I M12-175 study of venetoclax were published online today in the New England Journal of Medicine. The findings support the potential of venetoclax monotherapy for people with relapsed or refractory CLL, including those with 17p deletion.

AbbVie has submitted a New Drug Application (NDA) for venetoclax to the U.S. Food and Drug Administration (FDA) under breakthrough therapy designation (BTD), based in part on results of the M13-982 study. Venetoclax received BTD from the FDA earlier this year for the treatment of people with relapsed or refractory CLL harboring the 17p deletion. AbbVie has also submitted a marketing authorization application (MAA) to the European Medicines Agency (EMA). Submissions to other regulatory authorities around the world are planned in 2016.

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 patients with relapsed, refractory or previously untreated chronic lymphocytic leukemia (CLL) harboring the 17p deletion. The main study cohort included 107 patients with relapsed or refractory disease (all patients except for one had 17p deletion) and approximately 50 patients with relapsed, refractory or previously untreated disease have been enrolled in the safety expansion cohort. The primary endpoint of the study is overall response rate (ORR) as determined by an independent review committee (IRC), and secondary endpoints include complete response (CR), partial response (PR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). The level of minimal residual disease (MRD) in peripheral blood and/or bone marrow was assessed in a subset of patients.

About Study M12-175

M12-175 (NCT01328626) is a Phase I, open-label, multicenter study of venetoclax in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL) or non-Hodgkin’s lymphoma (NHL). The study involved an initial dose-escalation phase, followed by an expanded safety phase. The study enrolled approximately 116 patients with relapsed or refractory CLL or SLL, and approximately 95 patients with relapsed or refractory NHL. The primary endpoints of the study included safety, maximum tolerated dose (MTD) and recommended Phase II dose (RPTD). Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), overall survival (OS) and duration of response (DOR). The level of minimal residual disease (MRD) in peripheral blood and/or bone marrow was assessed in patients with CLL.

About Chronic Lymphocytic Leukemia (CLL)

CLL is one of the most common forms of blood cancer and in 2015, it is expected that there will be about 4,650 deaths from CLL in the United States. Most cases of CLL (95 percent) start in white blood cells called B-cells that have a protein called CD20 on their surface. In certain cases of CLL, a part of chromosome 17 is lost and along with it an important gene that controls apoptosis called p53. 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.

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 Genentech In Hematology

For more than 20 years, Genentech has been developing medicines with the goal to redefine 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, Genentech’s pipeline of investigational hematology medicines includes an anti-PDL1 antibody (atezolizumab/MPDL3280A), an anti-CD79b antibody drug conjugate (polatuzumab vedotin/RG7596), a small molecule antagonist of MDM2 (idasanutlin/RG7388) and in collaboration with AbbVie, a small molecule BCL-2 inhibitor (venetoclax/RG7601/GDC-0199/ABT-199). Genentech’s dedication to developing novel molecules in hematology expands beyond oncology, with the development of the investigational hemophilia A treatment emicizumab (ACE910).

About Genentech

Founded more than 35 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit