Roche Holding Ltd. : Genentech's Obinutuzumab (GA101) Significantly Reduced the Risk of Disease Progression or Death in People with One of the Most Common Forms of Blood Cancer

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced the first results from CLL11, a Phase III study of the investigational medicine GA101 which is being conducted in collaboration with the German CLL Study Group (GCLLSG). The CLL11 study compared the combination of either GA101 or Rituxan^® (rituximab) and chlorambucil, a standard chemotherapy, to chlorambucil alone in chronic lymphocytic leukemia (CLL). CLL is one of the most common forms of blood cancer and in 2013, it is expected that there will be nearly 5,000 deaths from CLL in the United States. The CLL11 study included elderly people with previously untreated CLL who were often not able to tolerate existing aggressive treatment options.

"People with CLL, particularly the elderly and those with additional medical problems, need new options," said Sandra Horning, M.D., global head, Clinical Development Hematology/Oncology. "As a former practicing hematologist, I believe GA101 has the potential to one day expand treatment options for people with CLL and we look forward to continuing to work with the FDA and health authorities around the world in an effort to bring GA101 to those in need."

GA101 combined with chlorambucil demonstrated a significant 86 percent reduction in the risk of disease progression, relapse or death. Additionally, the length of time during which people lived without their disease worsening (median progression-free survival, PFS) was more than doubled (23 months compared to 10.9 months, HR=0.14, 95 percent CI 0.09-0.21, p<.0001) when compared to chlorambucil alone. The full data, including the comparison of Rituxan plus chlorambucil with chlorambucil alone will be presented in an oral session at the 49th Annual Meeting of ASCO in Chicago on Tuesday, June 4.

"Roche has played a significant role in revolutionizing the treatment of blood cancers. With GA101, our aim was to design a unique antibody that kills cancer cells directly and engages the patient's own immune cells to help attack the cancerous cells," said Pablo Umaña, head of Roche Glycart AG.

GA101 is the first type II anti-CD20 medicine that is glycoengineered, which means specific sugar molecules in GA101 were modified (using GlycoMAb technology) to change its interaction with the body's immune cells with the goal of helping the immune system remove cancer cells from the body. In addition, as a type II anti-CD20 antibody, GA101 binds to CD20 with the aim of killing cancerous cells directly.

Based on the CLL11 data, marketing applications have been submitted to regulatory authorities including the European Medicines Association (EMA) and the FDA.

The FDA has granted GA101 Breakthrough Therapy Designation. This designation is designed to expedite the development and review of medicines intended to treat serious diseases and to help ensure patients have access to them through FDA approval as soon as possible.

Genentech will open an Expanded Access Program (EAP) to provide GA101 to people with CLL under certain circumstances while the company seeks regulatory approval.

About CLL11 Study (BO21004)

CLL11 is a Phase III, multicenter, open-label, randomized three-arm study investigating the safety and efficacy profile of either GA101 added to chlorambucil or Rituxan added to chlorambucil compared to chlorambucil alone in 781 previously untreated people with CLL and comorbidities (589 patients are included in this analysis and an additional 192 patients have been enrolled to enable the forthcoming direct comparison of GA101 versus Rituxan both in combination with chlorambucil). The study was conducted in collaboration with the GCLLSG. The primary endpoint of the study was PFS with secondary endpoints including overall response rate (ORR), overall survival (OS), disease-free survival (DFS), minimal residual disease (MRD) and safety profile. Specifically, the CLL11 trial data to be presented during ASCO showed the following:

• The addition of GA101 to chlorambucil led to a statistically significant reduction in the risk of disease progression or death of 86 percent (HR=0.14; p<.0001).
• The median PFS improved by more than a year from 10.9 months for chlorambucil alone to 23 months for GA101 plus chlorambucil. (see ** in table 1 below)
• The addition of Rituxan to chlorambucil significantly reduced the risk of disease progression or death during study follow-up by 68 percent (HR=0.32; p<.0001).
• Median PFS was 10.8 months for chlorambucil compared to 15.7 months for Rituxan plus chlorambucil.
• At this time, no formal comparison between the GA101 and Rituxan arms can be made as the number of PFS events required for that formal analysis has not yet been reached.
• No new safety signals were detected for either GA101 or Rituxan. The most common Grade 3-4 adverse events (AEs) for GA101 were infusion-related reactions (IRRs) and low cell count of certain white blood cells (neutropenia). The incidence and severity of IRRs decreased dramatically after the first infusion and no serious IRRs have been reported beyond the first infusion. The most common AEs are displayed in table 1 below.
• The most common AEs in the Rituxan arm were infections and neutropenia and are displayed in table 1 below.

Table 1: Summary of key efficacy and safety data

About Obinutuzumab (GA101)

GA101 is an investigational medicine that works with the body's immune system and is designed to attack cells that have a certain marker on their surface. GA101 is currently being investigated in a large clinical program, including multiple head-to-head Phase III studies versus Rituxan in indolent non-Hodgkin lymphoma (NHL) and diffuse large B-cell lymphoma (DLBCL).

Roche Glycart AG is a wholly-owned, independent research unit, part of Roche Pharma Research and Early Development.

About Genentech/Roche In Hematology

For more than 20 years, Genentech/Roche has been developing medicines that redefine treatment in hematology. Today, we're investing more than ever in our effort to bring innovative treatment options to people with cancers of the blood.

In addition to GA101, Genentech/Roche's pipeline of potential hematology medicines includes two antibody-drug conjugates (anti-CD79b [RG7596] and anti-CD22 [RG7593]), a small molecule antagonist of MDM2 (RG7112) and in collaboration with AbbVie, a small molecule BCL-2 inhibitor (RG7601/GDC-0199).

About Rituxan

Rituxan is a therapeutic antibody that binds to a specific protein called CD20 found on the surface of cancerous and normal B-cells. In CLL, NHL and rheumatoid arthritis (RA), Rituxan works with the body's own immune system to eliminate marked CD20-positive B-cells. Stem cells (those cells that give rise to B-cells) in bone marrow do not have the CD20 protein. B-cells usually regenerate after Rituxan treatment and return to normal levels in about 12 months for most patients.

Rituxan, discovered by Biogen Idec, first received FDA approval in November 1997 for the treatment of relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent. It was approved in the European Union under the trade name MabThera in June 1998.

INDICATIONS

Rituxan^® (rituximab) is indicated for the treatment of patients with:

• Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent
• Previously untreated follicular, CD20-positive, B-cell NHL in combination with first-line chemotherapy and, in patients achieving a complete or partial response to Rituxan in combination with chemotherapy, as single-agent maintenance therapy
• Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after first-line CVP chemotherapy
• Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens
• Previously untreated and previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide (FC)

Rituxan is not recommended for use in patients with severe, active infections.

Important Safety Information:

Rituxan can cause serious side effects that can lead to death, including: infusion reactions, tumor lysis syndrome (kidney failure due to fast breakdown of cancer cells), severe skin and mouth reactions, and progressive multifocal leukoencephalopathy (a rare, serious brain infection).

Rituxan has also been associated with serious and life threatening side effects, including: the return of active hepatitis B virus infection with sudden and serious liver problems including liver failure, and death, other serious infections that can lead to death, heart problems, kidney problems, and stomach and serious bowel problems including blockage and tears in the bowel, that can sometimes lead to death.

The most common side effects of Rituxan seen in patients with NHL were infusion reactions, fever, chills, low white blood cells, infections, body aches, and tiredness. The most common side effects of Rituxan in patients with CLL were infusion reactions and low white blood cells. Patients should talk to their doctor about their medical history before starting treatment with Rituxan.

Patients should tell their doctor about any side effect that bothers them or that does not go away. These are not all of the possible side effects with Rituxan.

Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Patients and caregivers may also report side effects to Genentech at (888) 835-2555.

Patients should read the Rituxan Full Prescribing Information including Boxed WARNINGS, and the Medication Guide at http://www.rituxan.com.

About Genentech

Founded more than 30 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 http://www.gene.com.

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