Monday, Feb 18, 2019

FDA Grants Priority Review to Genentech’s Polatuzumab Vedotin in Previously Treated Aggressive Lymphoma

Diffuse large B-cell lymphoma is an aggressive type of blood cancer that typically becomes harder to treat each time it returns

Polatuzumab vedotin has shown significant potential to improve outcomes in people living with this disease

South San Francisco, CA -- February 18, 2019 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) has accepted the company’s Biologics License Application (BLA) and granted Priority Review for polatuzumab vedotin in combination with bendamustine plus Rituxan ^® (rituximab) (BR) for the treatment of people with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). The FDA is expected to make a decision on approval by August 19, 2019.

“Polatuzumab vedotin, a potential first-in-class antibody drug conjugate, in combination with bendamustine and Rituxan, improved clinical outcomes including survival in some people with relapsed or refractory diffuse large B-cell lymphoma compared to bendamustine and Rituxan alone,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We are working with the FDA to bring this important new option to patients with this aggressive disease as quickly as possible."

The BLA is based on results of the GO29365 study, which showed that polatuzumab vedotin plus BR improved median overall survival compared to BR alone (12.4 vs. 4.7 months, HR=0.42; 95 percent CI 0.24-0.75; exploratory endpoint), in people with R/R DLBCL not eligible for a hematopoietic stem cell transplant. The study also showed that 40 percent of people treated with polatuzumab vedotin plus BR achieved a complete response (CR), while only 18 percent of people treated with BR alone achieved a CR (primary endpoint, as measured by positron emission tomography; CR rates assessed by independent review committee). A CR means no cancer could be detected at that time.

Priority Review designation is granted to medicines that the FDA considers to have the potential to provide significant improvements in the safety and effectiveness of the treatment, prevention or diagnosis of a serious disease. Polatuzumab vedotin was also granted Breakthrough Therapy Designation by the FDA and PRIME (PRIority MEdicines) designation by the European Medicines Agency for the treatment of people with R/R DLBCL in 2017. Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat a serious condition with preliminary evidence that indicates they may demonstrate substantial improvement over existing therapies.

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 bendamustine and Rituxan (rituximab) or Gazyva^® (obinutuzumab) 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).

• 40 percent of people treated with polatuzumab vedotin plus BR achieved a CR while only 18 percent of people treated with BR alone achieved a CR (primary endpoint, as measured by PET; CR rates assessed by IRC). A CR means no cancer could be detected at that time.
• Polatuzumab vedotin in combination with BR showed a median OS of over one year compared to the BR arm (12.4 vs. 4.7 months, HR=0.42; 95 percent CI 0.24-0.75), in people with R/R DLBCL not eligible for a hematopoietic stem cell transplant. OS was an exploratory endpoint.
• Polatuzumab vedotin plus BR increased median PFS and led to a 66 percent reduction in risk of disease worsening or death compared to BR alone (median PFS: 7.6 months vs. 2.0 months; HR=0.34; 95 percent CI 0.20-0.57).
• Patients treated with polatuzumab vedotin plus BR showed a longer time between first response to treatment and disease worsening than those receiving BR alone (investigator assessed median DOR: 10.3 months vs. 4.1 months; HR=0.44).
• Updated safety results are similar to those previously described, with infections and cytopenias remaining the most common Grade 3–4 adverse events (AEs). Polatuzumab vedotin plus BR had higher rates of Grade 3–4 cytopenias compared to BR, however, infection and transfusion rates remained similar between arms.

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 through 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 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 22,000 new cases of DLBCL will be diagnosed in 2019.

Rituxan Indications

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

• 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

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

Important Safety Information: 

Rituxan can cause serious side effects that can lead to death, including:

• Infusion Reactions: Infusion reactions are very common side effects of Rituxan treatment. Serious infusion reactions can happen during the patient’s infusion or within 24 hours after the patient’s infusion of Rituxan. The patient’s doctor should give the patient medicines before infusion of Rituxan to decrease the chance of having a severe infusion reaction.

Patients must tell their doctor or get medical help right away about any of these symptoms during or after an infusion of Rituxan:

• Hives (red itchy welts) or rash
• Itching
• Swelling of the lips, tongue, throat, or face
• Sudden cough
• Shortness of breath, difficulty breathing, or wheezing
• Weakness
• Dizziness or feel faint
• Palpitations (feel like the heart is racing or fluttering)
• Chest pain
• Severe Skin and Mouth Reactions:  Patients must tell their doctor or get medical help right away about any of these symptoms at any time during treatment with Rituxan:
  • Painful sores or ulcers on the skin, lips, or in the mouth
  • Blisters
  • Peeling skin
  • Rash
  • Pustules
• Hepatitis B Virus (HBV) Reactivation:  Before receiving Rituxan treatment, the patient’s doctor will do blood tests to check for HBV infection. If the patient has had hepatitis B or is a carrier of hepatitis B virus, receiving Rituxan could cause the virus to become an active infection again. Hepatitis B reactivation may cause serious liver problems, including liver failure, and death. The patient’s doctor will monitor for hepatitis B infection during and for several months after the patient stops receiving Rituxan.

Patients must tell their doctor right away about worsening tiredness, or yellowing of the skin or white part of the eyes during treatment with Rituxan.

• Progressive Multifocal Leukoencephalopathy (PML):  PML is a rare, serious brain infection caused by a virus that can happen in people who receive Rituxan. People with weakened immune systems can get PML. PML can result in death or severe disability. There is no known treatment, prevention, or cure for PML.

Patients must tell their doctor right away about new or worsening symptoms or if anyone close to the patient notices these symptoms:

• Confusion
• Dizziness or loss of balance
• Difficulty walking or talking
• Decreased strength or weakness on one side of the body
• Vision problems, such as blurred vision or loss of vision

What should patients tell their doctor before receiving Rituxan? 

Before receiving Rituxan, patients should tell their doctor if they:

• Have had a severe reaction to Rituxan or a rituximab product
• Have a history of heart problems, irregular heartbeat, or chest pain
• Have lung or kidney problems
• Have had an infection, currently have an infection, or have a weakened immune system
• Have or have had any severe infections including:
  • Hepatitis B virus (HBV)
  • Hepatitis C virus (HCV)
  • Cytomegalovirus (CMV)
  • Herpes simplex virus (HSV)
  • Parvovirus B19
  • Varicella zoster virus (chickenpox or shingles)
  • West Nile Virus
• Have had a recent vaccination or are scheduled to receive vaccinations. Patients should not receive certain vaccines before or during treatment with Rituxan
• Have any other medical conditions
• Are pregnant or plan to become pregnant. Patients must talk to their doctor about the risks to the patient’s unborn baby if receiving Rituxan during pregnancy. Females who are able to become pregnant should use effective birth control (contraception) during treatment with Rituxan and for 12 months after the last dose of Rituxan. Patients should talk to their doctor about effective birth control. Patients should tell their doctor right away if they become pregnant or think that they are pregnant during treatment with Rituxan
• Are breastfeeding or plan to breastfeed. It is not known if Rituxan passes into the breast milk. Do not breastfeed during treatment and for at least 6 months after the last dose of Rituxan
• Are taking any medications, including prescription and over-the-counter medicines, vitamins, and herbal supplements

What are the possible side effects of Rituxan? 

Rituxan can cause serious side effects, including:

• Tumor Lysis Syndrome (TLS):  TLS is caused by the fast breakdown of cancer cells. TLS can cause the patient to have:
  • Kidney failure and the need for dialysis treatment
  • Abnormal heart rhythm

TLS can happen within 12 to 24 hours after an infusion of Rituxan. The patient’s doctor may do blood tests to check for TLS. The patient’s doctor may give medicine to help prevent TLS. Patients must tell their doctor right away if they have any of the following signs or symptoms of TLS:

• Nausea
• Vomiting
• Diarrhea
• Lack of energy
• Serious Infections:  Serious infections can happen during and after treatment with Rituxan, and can lead to death. Rituxan can increase the patient’s risk of getting infections and can lower the ability of the patient’s immune system to fight infections. Types of serious infections that can happen with Rituxan include bacterial, fungal, and viral infections. After receiving Rituxan, some people have developed low levels of certain antibodies in their blood for a long period of time (longer than 11 months). Some of these patients with low antibody levels developed infections. People with serious infections should not receive Rituxan. Patients must tell their doctor right away if they have any symptoms of infection:
  • Fever
  • Cold symptoms, such as runny nose or sore throat that do not go away
  • Flu symptoms, such as cough, tiredness, and body aches
  • Earache or headache
  • Pain during urination
  • Cold sores in the mouth or throat
  • Cuts, scrapes, or incisions that are red, warm, swollen, or painful
• Heart Problems:  Rituxan may cause chest pain, irregular heartbeats, and heart attack. The patient’s doctor may monitor the patient’s heart during and after treatment with Rituxan if they have symptoms of heart problems or have a history of heart problems. Patients must tell their doctor right away if they have chest pain or irregular heart-beats during treatment with Rituxan.
• Kidney Problems:  especially if the patient is receiving Rituxan for non-Hodgkin’s lymphoma. Rituxan can cause severe kidney problems that lead to death. The patient’s doctor should do blood tests to check how well their kidneys are working.
• Stomach and Serious Bowel Problems That Can Sometimes Lead to Death:  Bowel problems, including blockage or tears in the bowel can happen if the patient receives Rituxan with chemotherapy medicines. Patients must tell their doctor right away if they have any stomach-area (abdomen) pain or repeated vomiting during treatment with Rituxan.

The patient’s doctor will stop treatment with Rituxan if they have severe, serious, or life-threatening side effects. 

What are the most common side effects during treatment with Rituxan? 

• Infusion-related reactions
• Infections (may include fever, chills)
• Body aches
• Tiredness
• Nausea

Other side effects include:

• Aching joints during or within hours of receiving an infusion
• More frequent upper respiratory tract infections

These are not all of the possible side effects with Rituxan.

Please see the Rituxan full Prescribing Information, including the Medication Guide, for additional Important Safety Information at http://www.rituxan.com/.

Report side effects to the FDA at (800) FDA-1088 or https://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. 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 and 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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