Sunday, Dec 10, 2017

Phase II Data Showed Genentech’s Investigational Polatuzumab Vedotin Plus Bendamustine and Rituxan (BR) Increased Complete Response Rates Compared to BR Alone in Previously Treated Aggressive Lymphoma

Polatuzumab vedotin combination demonstrated improvements across multiple efficacy measures compared to BR alone in relapsed or refractory diffuse large B-cell lymphoma

These data led to FDA Breakthrough Therapy and EMA PRIME (PRIority MEdicines) designations

Results will be presented at the 59th American Society of Hematology Annual Meeting

South San Francisco, CA -- December 10, 2017 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today positive results from the randomized Phase II GO29365 study that compared polatuzumab vedotin in combination with bendamustine plus Rituxan^® (rituximab) (BR) against BR alone in people with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not candidates for hematopoietic stem cell transplant. The study met its primary endpoint, demonstrating that the addition of polatuzumab vedotin to BR increased complete response (CR) rates from 15 percent to 40 percent (p=0.012) at the end of treatment, as measured by positron emission tomography (PET) and assessed by an independent review committee (IRC). No unexpected safety signals were observed with the addition of polatuzumab vedotin to BR.

“As many as 40 percent of people with diffuse large B-cell lymphoma do not respond to initial therapy or experience the return of their disease, at which point their treatment options are limited and the prognosis is very poor,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “The promising efficacy observed for polatuzumab vedotin in this study supports its potential as a new treatment option for people previously treated for this aggressive blood cancer, and we look forward to discussing the results with health authorities.”

The data will be presented in a poster session on Sunday, December 10 at the 59^th American Society of Hematology (ASH) Annual Meeting by Laurie Sehn, M.D., British Columbia Cancer Agency/University of British Columbia. The results showed:

• Polatuzumab vedotin plus BR significantly improved CR rates from 15 percent with BR alone to 40 percent (p=0.012), as measured by PET and assessed by IRC. A CR means no cancer could be detected at that time.
• The benefit observed was consistent across secondary endpoints, including improvements in investigator-assessed best objective response (OR; CR and partial response, PR) and CR with polatuzumab vedotin plus BR (70.0 percent OR, 57.5 percent CR) compared to BR alone (32.5 percent OR, 20.0 percent CR).
• Exploratory endpoints also improved with the addition of polatuzumab vedotin to BR:
  • Patients treated with polatuzumab vedotin plus BR lived longer than those receiving BR alone (median overall survival; 11.8 months vs. 4.7 months; HR=0.35; 95 percent CI 0.19-0.67; p=0.0008).
  • The addition of polatuzumab vedotin also increased the time until disease worsening or death (median progression-free survival: 6.7 months vs. 2.0 months; HR=0.31; 95 percent CI 0.18-0.55; p<0.0001), and the time between first response to treatment and disease worsening (duration of response: 8.8 months vs. 3.7 months).
• No unexpected safety signals were observed with the addition of polatuzumab vedotin to BR. The most common Grade 3-4 adverse events with polatuzumab vedotin plus BR compared to BR alone, respectively, were low white blood cell count (46.2 percent vs. 35.9 percent), low white blood cell count with fever (10.3 percent vs. 5.1 percent), low platelet count (33.3 percent vs. 20.5 percent), anemia (25.6 percent vs. 12.8 percent) and infections (17.9 percent vs. 17.9 percent).

Based on results from this study, polatuzumab vedotin was recently granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration and PRIME (PRIority MEdicines) designation by the European Medicines Agency for the treatment of people with relapsed or refractory DLBCL. There are a number of ongoing studies evaluating the efficacy and safety of polatuzumab vedotin for several types of non-Hodgkin’s lymphoma, including combinations with Gazyva^® (obinutuzumab), Rituxan, Venclexta™ (venetoclax) and Tecentriq^® (atezolizumab).

About the GO29365 study

GO29365 is a global, Phase Ib/II randomized study evaluating the safety, tolerability and activity of polatuzumab vedotin in combination with Rituxan or Gazyva plus bendamustine in relapsed or refractory (R/R) follicular lymphoma or diffuse large B-cell lymphoma (DLBCL). The Phase II stage randomized 80 patients with heavily pre-treated R/R DLBCL to receive either bendamustine plus Rituxan (BR), or BR in combination with polatuzumab vedotin. Patients enrolled had received a median of two prior therapies (a range of 1-7 prior therapies in the polatuzumab vedotin arm and range of 1-5 prior therapies in the BR alone arm). The primary endpoint was complete response (CR) at the end of treatment, as measured by positron emission tomography (PET) and assessed by an independent review committee (IRC). Secondary endpoints included objective response (OR; CR and partial response, PR) by investigator assessment and best objective response at the end of treatment by investigator and IRC assessment. Exploratory endpoints included duration of response (DOR), progression-free survival (PFS), event-free survival (EFS) and overall survival (OS).

About polatuzumab vedotin

Polatuzumab vedotin is a first-in-class anti-CD79b antibody drug conjugate (ADC) currently being investigated for the treatment of several types of non-Hodgkin’s lymphoma (NHL). The CD79b protein is highly specific and expressed in the majority of types of B-cell NHL, making it a promising target for the development of new therapies. Polatuzumab vedotin binds to CD79b and destroys these B-cells via a targeted approach, which is thought to minimize the effects on normal cells while maximizing tumor cell death. Polatuzumab vedotin is being developed by Genentech, a member of the Roche Group, utilizing Seattle Genetics ADC technology.

About DLBCL

Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin’s lymphoma (NHL), accounting for about one in three cases of NHL. DLBCL is an aggressive (fast-growing) type of NHL. As many as 40 percent of patients will relapse, at which point their prognosis is poor. In the United States, it is estimated that more than 21,000 new cases of DLBCL will be diagnosed in 2017.

Rituxan Indications

Rituxan^® (rituximab) injection, for intravenous use, is indicated for the treatment of patients with:

• Low-grade or follicular CD20-positive non-Hodgkin’s lymphoma as a single-agent therapy in patients whose disease recurred or did not respond to initial treatment
• Follicular CD20-positive non-Hodgkin’s lymphoma as an initial treatment with chemotherapy, and in patients whose initial treatment was successful, as a single-agent follow-up therapy
• Low-grade CD20-positive non-Hodgkin’s lymphoma as a single-agent follow-up therapy for patients who did not progress on initial treatment with CVP chemotherapy
• CD20-positive diffuse large B-cell non-Hodgkin’s lymphoma as an initial treatment in combination with CHOP chemotherapy
• CD20-positive chronic lymphocytic leukemia in combination with FC chemotherapy as an initial treatment or as a treatment after disease has recurred

People with serious infections should not receive Rituxan.

It is not known if Rituxan is safe or effective in children.

Important Safety Information:

Patients must tell their doctor right away about any side effects they experience. Rituxan can cause serious side effects that can lead to death, including:

• Infusion Reactions: may occur during or within 24 hours of the infusion. The patient’s doctor should give the patient medicines before their treatment. Symptoms can include hives, rash, itching, facial or oral swelling, sudden cough, shortness of breath, difficulty breathing, weakness, dizziness, feeling faint, racing heart, or chest pain.
• Severe Skin and Mouth Reactions: symptoms can include painful sores, ulcers, or blisters on the skin, lips or mouth; peeling skin; rash; or pustules.
• Hepatitis B Virus (HBV) Reactivation: may cause serious liver problems including liver failure and death. If patients have had hepatitis B or are carriers of HBV, receiving Rituxan could cause the virus to become an active infection again. Patients should not receive Rituxan if they have active HBV liver disease. The patient’s doctor will do blood tests to check for HBV infection prior to treatment and will monitor the patient during and for several months following their treatment.
• Progressive Multifocal Leukoencephalopathy (PML): a rare, serious brain infection that can lead to severe disability and death and for which there is no known prevention, treatment or cure. Symptoms can include difficulty thinking, loss of balance, changes in speech or walking, weakness on one side of the body, or blurred or lost vision.

Additional possible serious side effects of Rituxan:

Patients must tell their doctor right away about any side effects they experience. Rituxan can cause serious side effects that can lead to death, including:

• Tumor Lysis Syndrome (TLS): may cause kidney failure and the need for dialysis treatment, abnormal heart rhythm, and can lead to death. The patient’s doctor may give the patient medicines before their treatment to help prevent TLS.
• Serious Infections: can happen during and after treatment and can lead to death. These infections may be bacterial, fungal, or viral. Symptoms can include fever; cold or flu symptoms; earache or headache; pain during urination; white patches in the mouth or throat; cuts or scrapes that are red, warm, swollen or painful.
• Heart Problems: symptoms can include chest pain and irregular heartbeats that may require treatment. The patient’s doctor may need to stop their treatment.
• Kidney Problems: the patient’s doctor should do blood tests to check how well the patient’s kidneys are working.
• Stomach and Serious Bowel Problems: can include blockage or tears in the bowel that can lead to death. Stomach area pain during treatment can be a symptom.
• Low Blood Cell Counts: the patient’s blood cell counts may be monitored during treatment.

The most common side effects of Rituxan are infusion reactions, chills, infections, body aches, tiredness, and low white blood cells.

Other side effects with Rituxan include:

• aching joints during or within hours of receiving an infusion
• more frequent upper respiratory tract infection

Patients must tell their doctor if they are pregnant, plan to become pregnant, or are breastfeeding. It is not known if Rituxan may harm the patient’s unborn baby or pass into the patient’s breast milk. Women should use birth control while using Rituxan and for 12 months after treatment.

Patients must 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 of Rituxan. For more information, patients should ask their doctor or pharmacist.

Please visit http://www.Rituxan.com for the Rituxan full Prescribing Information, including BOXED WARNINGS and the Medication Guide, for additional Important Safety Information.

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

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 polatuzumab vedotin (RG7596) and a small molecule antagonist of MDM2 (idasanutlin/RG7388). For more information visit http://www.gene.com/hematology .

About Genentech

Founded more than 40 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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