Tuesday, Dec 12, 2017

Genentech Announces Phase III Data Showing Venclexta plus Rituxan Reduced the Risk of Disease Progression or Death by 83 Percent Compared to a Standard of Care Regimen in Previously Treated Chronic Lymphocytic Leukemia

This chemotherapy-free combination showed improvements across multiple efficacy measures compared to bendamustine plus Rituxan in the pivotal MURANO trial

Results will be presented during the Late-Breaking Abstracts Session at the 59th American Society of Hematology Annual Meeting

South San Francisco, CA -- December 12, 2017 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced the first results from the pivotal Phase III MURANO study evaluating Venclexta™ (venetoclax) plus Rituxan^® (rituximab) compared to bendamustine plus Rituxan (BR) for the treatment of people with relapsed or refractory chronic lymphocytic leukemia (CLL). 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, as assessed by investigator) by 83 percent compared with BR (HR=0.17; 95 percent CI 0.11-0.25; p<0.0001). No new safety signals were observed. Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the United States and commercialized by AbbVie outside of the United States.

“The MURANO study results indicate that Venclexta plus Rituxan has the potential to provide an important new chemotherapy-free option for people with previously treated chronic lymphocytic leukemia,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We are particularly encouraged by the magnitude of benefit observed across key efficacy measures compared to a current standard of care, and we look forward to discussing these results with health authorities.”

Results from the study were featured in the official press program of the 59^th American Society of Hematology (ASH) Annual Meeting in Atlanta on Monday, December 11, and will be presented during the Late-Breaking Abstracts Session on Tuesday, December 12 at 7:45 A.M. EST by John F. Seymour, M.D., Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia (Abstract #LBA-2).

Data from the MURANO study will be submitted to global health authorities, including the U.S. Food and Drug Administration (FDA), which has granted Breakthrough Therapy Designation for Venclexta in combination with Rituxan for the treatment of relapsed or refractory CLL based on promising results from the Phase Ib M13-365 study.

Venclexta was granted accelerated approval by the FDA in April 2016 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 MURANO study is part of the company’s commitment in the United States to convert the current accelerated approval of Venclexta to a full approval.

A robust clinical development program for Venclexta is ongoing, and additional results across multiple blood cancers including acute myeloid leukemia (AML) and multiple myeloma (MM) were also presented at the ASH Annual Meeting. 

About the MURANO study

MURANO (NCT02005471) is a Phase III open-label, international, multicenter, randomized 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. The study included 389 patients with relapsed or refractory chronic lymphocytic leukemia (CLL) who had been previously treated with at least one, but not more than three, lines of therapy. Patients were randomly assigned in a 1:1 ratio to receive either Venclexta plus Rituxan (Arm A) or BR (Arm B). The primary endpoint of the study is investigator-assessed progression-free survival (PFS). Secondary endpoints include PFS assessed by independent review committee (IRC), overall response rate (ORR), complete response rate (with or without complete blood count recovery, CR/CRi), overall survival (OS), minimal residual disease (MRD) status, duration of response, event-free survival and time to next CLL treatment. The results showed:

• Patients in the study who received Venclexta plus Rituxan lived significantly longer without their disease worsening (PFS, as assessed by investigator) compared to those who received BR (HR=0.17; 95 percent CI 0.11-0.25; p<0.0001; median PFS: not reached vs. 17.0 months, respectively).
  • At two years, 84.9 percent of patients in the Venclexta plus Rituxan arm had not experienced disease progression, compared to 36.3 percent of patients in the BR arm.
  • Consistent benefit was observed in all patient subgroups for Venclexta plus Rituxan compared to BR, including high-risk and low-risk groups.
  • IRC assessment was consistent; as assessed by IRC, Venclexta plus Rituxan reduced the risk of disease progression or death by 81 percent compared to BR (HR=0.19; 95 percent CI 0.13-0.28; p<0.0001).
• Clinical benefit observed for Venclexta plus Rituxan compared to BR was consistent across key secondary endpoints, including OS (HR=0.48; 95 percent CI 0.25-0.90; medians not yet reached), ORR as assessed by investigator (93.3 percent vs. 67.7 percent) and CR/CRi as assessed by investigator (26.8 percent vs. 8.2 percent). These results were not statistically significant. In addition, higher rates of MRD-negativity at any time were observed with Venclexta plus Rituxan compared to BR (83.5 percent vs. 23.1 percent). MRD-negativity was defined as less than 1 CLL cell in 10,000 leukocytes.
• No new safety signals were observed with the treatment combination of Venclexta plus Rituxan. The most common Grade 3-4 adverse events with Venclexta plus Rituxan compared to BR, respectively, were low white blood cell count (57.7 percent vs. 38.8 percent), low red blood cell count (10.8 percent vs. 13.8 percent), low platelet count (5.7 percent vs. 10.1 percent), low white blood cell count with fever (3.6 percent vs. 9.6 percent), pneumonia (5.2 percent vs. 8.0 percent) and infusion reactions (1.5 percent vs. 5.3 percent).

About CLL

Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia, and in 2017, it is estimated there will be more than 20,000 new cases of CLL diagnosed in the United States. Although signs of CLL may disappear for a period of time after initial treatment, the disease is considered incurable and many people will require additional treatment due to the return of cancerous cells.

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 signaling system that tells cells, including cancer cells, to self-destruct. Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the United States and commercialized by AbbVie 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 leukemia (AML) ineligible for intensive chemotherapy; and in combination with low-dose cytarabine (LDAC) for people with untreated AML ineligible for intensive chemotherapy.

Venclexta Indication

Venclexta™ (venetoclax) is a prescription medicine used to treat people with chronic lymphocytic leukemia (CLL) with 17p deletion who have received at least one prior treatment.

Venclexta was approved based on response rate. There is an ongoing study to find out how Venclexta works over a longer period of time.

It is not known if Venclexta is safe and effective in children.

Important Safety Information

Patients must tell their doctor right away about any side effects they experience.

Venclexta can cause serious side effects, including tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. A patient’s doctor will do tests for TLS. It is important for patients taking Venclexta to keep their appointments for blood tests. Patients will receive other medicines before starting and during treatment with Venclexta to help reduce their risk of TLS. Patients may also need to receive intravenous (IV) fluids into their vein. Patients taking Venclexta should tell their doctor right away if they have any symptoms of TLS during treatment with Venclexta, including fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness or muscle pain or joint pain.

Patients should drink plenty of water when taking Venclexta to help reduce the risk of getting TLS. Patients should drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before their first dose, on the day of their first dose of

Venclexta, and each time the dose is increased.

Certain medicines must not be taken when patients first start taking Venclexta and while their dose is being slowly increased.

• Patients should tell their doctor about all the medicines they take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. Venclexta and other medicines may affect each other, causing serious side effects.
• Patients should not start new medicines during treatment with Venclexta without first talking with their doctor

Before taking Venclexta, patients should tell their doctor about all of their medical conditions, including if they:

• Have any kidney or liver problems.
• Have problems with their body salts or electrolytes, such as potassium, phosphorus, or calcium.
• Have a history of high uric acid levels in their blood or gout.
• Are scheduled to receive a vaccine. Patients should not receive a “live vaccine” before, during, or after treatment with Venclexta, until their doctor tells them it is okay. If a patient is unsure about the type of immunization or vaccine, they should ask their doctor. These vaccines may not be safe or may not work as well during treatment with Venclexta.
• Are pregnant or plan to become pregnant. Venclexta may harm an unborn baby. If a patient is able to become pregnant, the doctor should do a pregnancy test before they start treatment with Venclexta, and they should use effective birth control during treatment and for 30 days after the last dose of Venclexta.
• Are breastfeeding or plan to breastfeed. It is not known if Venclexta passes into breast milk. Patients should not breastfeed during treatment with Venclexta.

Patients taking Venclexta should not drink grapefruit juice or eat grapefruit, Seville oranges (often used in marmalades), or starfruit while they are taking Venclexta. These products may increase the amount of Venclexta in the patient’s blood.

Venclexta can cause serious side effects, including:

• Low White Blood Cell Count (neutropenia): Low white blood cell counts are common with Venclexta, but can also be severe. A doctor will do blood tests to check a patient’s blood counts during treatment with Venclexta. Patients should tell their doctor right away if they have a fever or any signs of an infection.

The most common side effects of Venclexta include low white blood cell count, diarrhea, nausea, low red blood cell count, upper respiratory tract infection, low platelet count, and feeling tired.

Venclexta may cause fertility problems in males. This may affect the ability to father a child. Patients should talk to their doctor if they have concerns about fertility.

These are not all the possible side effects of Venclexta. Patients should tell their doctor if they have any side effect that bothers them or that does not go away.

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.

Please visit http://www.Venclexta.com for the Venclexta full Prescribing Information, including Patient Information, for additional Important Safety Information.

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 patienst 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 an anti-CD79b antibody drug conjugate (polatuzumab vedotin/RG7596) and a small molecule antagonist of MDM2 (idasanutlin/RG7388). For more information visithttp://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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