FDA Approves Genentech’s Polivy in Combination With R-CHP for People With Certain Types of Previously Untreated Diffuse Large B-cell Lymphoma

– Polivy combination is the first FDA-approved therapy in nearly 20 years for the first-line treatment of diffuse large B-cell lymphoma, an aggressive disease and the most common form of non-Hodgkin’s lymphoma in the U.S. –

– POLARIX trial showed the Polivy combination reduced the risk of disease progression, relapse or death by 27% compared to the standard of care, R-CHOP, with a comparable safety profile –

– First-line treatment with Polivy plus R-CHP has the potential to reduce the burden on patients and healthcare systems, associated with disease progression –

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the U.S. Food and Drug Administration (FDA) has approved Polivy^® (polatuzumab vedotin-piiq) in combination with Rituxan^® (rituximab), cyclophosphamide, doxorubicin and prednisone (R-CHP) for the treatment of adult patients who have previously untreated diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) or high-grade B-cell lymphoma (HGBL) and who have an International Prognostic Index (IPI) score of two or greater. This FDA decision converts the accelerated approval of Polivy in combination with bendamustine and Rituxan for relapsed or refractory (R/R) DLBCL after at least two prior therapies to regular approval.

DLBCL is an aggressive, hard-to-treat disease and is the most common form of non-Hodgkin’s lymphoma in the United States. Approximately 31,000 people in the U.S. are projected to be diagnosed with DLBCL in 2023. Limited progress has been made in improving patient outcomes in previously untreated DLBCL over the last two decades. While many patients are responsive to initial treatment, as many as four in 10 people with DLBCL do not respond or relapse. For people who undergo initial treatment with the standard of care, Rituxan plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), most relapses occur within two years of starting treatment, and the majority of those who require subsequent lines of therapy have poor outcomes.

“It has been nearly 20 years since a new treatment option has become available to people newly diagnosed with diffuse large B-cell lymphoma,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “Today’s decision from the FDA to approve Polivy in combination with R-CHP in this setting brings a much-needed new treatment option which may improve outcomes and bring other benefits to many patients with this aggressive lymphoma.”

The FDA approval of Polivy plus R-CHP for the first-line treatment of DLBCL is based on pivotal data from POLARIX, an international Phase III, randomized, double-blind, placebo-controlled study that demonstrated a statistically significant and clinically meaningful improvement in PFS compared to R-CHOP. The risk of disease progression, relapse or death was reduced by 27% with Polivy plus R-CHP (n=440) compared with R-CHOP (n=439; hazard ratio [HR] 0.73; 95% confidence interval [CI]: 0.57–0.95; p<0.02). The safety profile was comparable for Polivy plus R-CHP versus R-CHOP, including rates of Grade 3-4 adverse events (AEs; 57.7% versus 57.5%), serious AEs (34.0% versus 30.6%), Grade 5 AEs (3.0% versus 2.3%), and AEs leading to dose reduction (9.2% versus 13.0%). The most common AEs were peripheral neuropathy, nausea, fatigue, diarrhea, constipation, alopecia, and mucositis. The most common Grade 3-4 AEs were lymphopenia and neutropenia.

This approval follows the FDA Oncologic Drugs Advisory Committee (ODAC) vote of 11 to 2 in favor of Polivy in combination with R-CHP for previously untreated DLBCL. More than 70 countries have approved this Polivy combination for the treatment of adult patients with previously untreated DLBCL, including in the EU, UK, Japan, Canada and China. Polivy in combination with R-CHP was recently added to the National Comprehensive Cancer Network^® (NCCN^®) Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) as a category 1, preferred regimen for first-line DLBCL. Polivy in combination with bendamustine and Rituxan is currently approved in more than 80 countries worldwide for the treatment of adults with relapsed or refractory (R/R) DLBCL after one or more prior therapies, including in the U.S.

Genentech continues to explore areas of unmet need where Polivy has the potential to deliver additional benefit, including in ongoing studies investigating combinations of Polivy with the company’s CD20xCD3 T-cell engaging bispecific antibodies Lunsumio^® (mosunetuzumab-axgb) or glofitamab. Trials include the Phase III SUNMO study in combination with Lunsumio in patients with R/R DLBCL and the Phase III POLARGO study with Rituxan in combination with gemcitabine and oxaliplatin in patients with R/R DLBCL.

Genentech is committed to helping people access the medicines they are prescribed and offers comprehensive services for people prescribed Polivy to help minimize barriers to access and reimbursement. For people who qualify, Genentech offers patient assistance programs through Genentech Access Solutions. More information is also available at 866-4ACCESS/866-422-2377 or http://www.Genentech-Access.com.

About the POLARIX Study

POLARIX [NCT03274492] is an international Phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy, safety and pharmacokinetics of Polivy^® (polatuzumab vedotin-piiq) plus Rituxan^® (rituximab), cyclophosphamide, doxorubicin and prednisone (R-CHP) versus Rituxan, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in people with previously untreated diffuse large B-cell lymphoma (DLBCL). Eight-hundred and seventy-nine patients were randomized 1:1 to receive either Polivy plus R-CHP plus a vincristine placebo for six cycles, followed by Rituxan for two cycles; or R-CHOP plus a Polivy placebo for six cycles, followed by two cycles of Rituxan. The primary outcome measure is progression-free survival as assessed by the investigator using the Lugano Response Criteria for malignant lymphoma. POLARIX is being conducted in collaboration with The Lymphoma Study Association (LYSA) and The Lymphoma Academic Research Organisation (LYSARC).

About Diffuse Large B-Cell Lymphoma

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. While it is generally responsive to treatment in the frontline, as many as 40% of people will relapse or have refractory disease, at which time salvage therapy options are limited and survival is short. Approximately 160,000 people worldwide are estimated to be diagnosed with DLBCL each year.

About Polivy^® (polatuzumab vedotin-piiq)

Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B cells, an immune cell impacted in some types of non-Hodgkin’s lymphoma (NHL), making it a promising target for the development of new therapies. Polivy binds to cancer cells such as CD79b and destroys these B cells through the delivery of an anti-cancer agent, which is thought to minimize the effects on normal cells. Polivy is being developed by Genentech using Seagen ADC technology and is currently being investigated for the treatment of several types of NHL.

Polivy U.S. Indication

POLIVY is a prescription medicine used with other medicines (a rituximab product, cyclophosphamide, doxorubicin, and prednisone) as a first treatment for adults who have moderate to high risk diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) or high-grade B-cell lymphoma (HGBL).

Important Safety Information

Possible serious side effects

Everyone reacts differently to POLIVY therapy, so it’s important to know what the side effects are. Some people who have been treated with POLIVY have experienced serious to fatal side effects. Your doctor may stop or adjust your treatment if any serious side effects occur. Be sure to contact your healthcare team if there are any signs of these side effects.

• Nerve problems in your arms and legs: This may happen as early as after your first dose and may worsen with every dose. Your doctor will monitor for signs and symptoms, such as changes in your sense of touch, numbness or tingling in your hands or feet, nerve pain, burning sensation, any muscle weakness, or changes to your walking pattern
• Infusion-related reactions: You may experience fever, chills, rash, breathing problems, low blood pressure, or hives within 24 hours of your infusion
• Low blood cell counts: Treatment with POLIVY can cause severe low blood cell counts. Your doctor will monitor your blood counts throughout treatment with POLIVY
• Infections: If you have a fever of 100.4°F (38°C) or higher, chills, cough, or pain during urination, contact your healthcare team. Your doctor may also give you medication before giving you POLIVY, which may prevent some infections
• Rare and serious brain infections: Your doctor will monitor closely for signs and symptoms of these types of infections. Contact your doctor if you experience confusion, dizziness or loss of balance, trouble talking or walking, or vision changes
• Tumor lysis syndrome: Caused by the fast breakdown of cancer cells. Signs include nausea, vomiting, diarrhea, and lack of energy
• Potential harm to liver: Some signs include tiredness, weight loss, pain in the abdomen, dark urine, and yellowing of your skin or the white part of your eyes. You may be at higher risk if you already had liver problems or you are taking other medication

Side effects seen most often

The most common side effects during treatment were

• Nerve problems in arms and legs
• Nausea
• Tiredness or lack of energy
• Diarrhea
• Constipation
• Hair loss
• Redness and sores of the lining of the mouth, lips, throat, and digestive tract

POLIVY may lower your red or white blood cell counts and increase uric acid levels.

POLIVY may not be for everyone. Talk to your doctor if you are

• Pregnant or think you are pregnant: Data have shown that POLIVY may harm your unborn baby
• Planning to become pregnant: Women should avoid getting pregnant while taking POLIVY. Women should use effective contraception during treatment and for 3 months after their last POLIVY treatment. Men taking POLIVY should use effective contraception during treatment and for 5 months after their last POLIVY treatment
• Breastfeeding: Women should not breastfeed while taking POLIVY and for 2 months after the last dose

These may not be all the side effects. Talk to your healthcare provider for more information about the benefits and risks of POLIVY treatment.

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

Please see the full Prescribing Information and visit https://www.POLIVY.com for additional Important Safety Information.

About Lunsumio^® (mosunetuzumab-axgb)

Lunsumio is a first-in-class CD20xCD3 T-cell engaging bispecific antibody designed to target CD20 on the surface of B cells and CD3 on the surface of T cells. This dual targeting activates and redirects a patient’s existing T cells to engage and eliminate target B cells by releasing cytotoxic proteins into the B cells. A robust clinical development program for Lunsumio is ongoing, investigating the molecule as a monotherapy and in combination with other medicines, for the treatment of people with B-cell non-Hodgkin’s lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma, and other blood cancers.

Lunsumio U.S. Indication

LUNSUMIO (mosunetuzumab-axgb) is a prescription medicine used to treat adults with follicular lymphoma whose cancer has come back or did not respond to previous treatment, and who have already received two or more treatments for their cancer.

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

The conditional approval of LUNSUMIO is based on response rate. There are ongoing studies to establish how well the drug works.

What is the most important information I should know about LUNSUMIO?

LUNSUMIO may cause Cytokine Release Syndrome (CRS), a serious side effect that is common during treatment with LUNSUMIO and can also be severe or life-threatening.

Get medical help right away if you develop any signs or symptoms of CRS at any time, including:

• fever of 100.4°F (38°C) or higher
• chills
• low blood pressure
• fast or irregular heartbeat
• tiredness or weakness
• difficulty breathing
• headache
• confusion
• feeling anxious
• dizziness or light-headedness
• nausea
• vomiting

Due to the risk of CRS, you will receive LUNSUMIO on a “step-up dosing schedule.”

• The step-up dosing schedule is when you receive smaller “step-up” doses of LUNSUMIO on Day 1 and Day 8 of your first cycle of treatment
• You will receive a higher dose of LUNSUMIO on Day 15 of your first cycle of treatment
• If your dose of LUNSUMIO is delayed for any reason, you may need to repeat the step-up dosing schedule
• Before each dose in Cycle 1 and Cycle 2, you will receive medicines to help reduce your risk of CRS

Your healthcare provider will check you for CRS during treatment with LUNSUMIO and may treat you in a hospital if you develop signs and symptoms of CRS. Your healthcare provider may temporarily stop or completely stop your treatment with LUNSUMIO, if you have severe side effects.

What are the possible side effects of LUNSUMIO?

LUNSUMIO may cause serious side effects, including:

• Neurologic problems. Your healthcare provider will check you for neurologic problems during treatment with LUNSUMIO. Your healthcare provider may also refer you to a healthcare provider who specializes in neurologic problems. Tell your healthcare provider right away if you develop any signs or symptoms of neurologic problems during or after treatment with LUNSUMIO, including:
  • headache
  • numbness and tingling of the arms, legs, hands, or feet
  • dizziness
  • confusion and disorientation
  • difficulty paying attention or understanding things
  • forgetting things or forgetting who or where you are
  • trouble speaking, reading, or writing
  • sleepiness or trouble sleeping
  • tremors
  • loss of consciousness
  • seizures
  • muscle problems or muscle weakness
  • loss of balance or trouble walking

• Serious infections. LUNSUMIO can cause serious infections that may lead to death. Your healthcare provider will check you for signs and symptoms of infection before and during treatment. Tell your healthcare provider right away if you develop any signs or symptoms of infection during treatment with LUNSUMIO, including:
  • fever of 100.4°F (38°C) or higher
  • cough
  • chest pain
  • tiredness
  • shortness of breath
  • painful rash
  • sore throat
  • pain during urination
  • feeling weak or generally unwell

• Low blood cell counts. Low blood cell counts are common during treatment with LUNSUMIO and can also be severe. Your healthcare provider will check your blood cell counts during treatment with LUNSUMIO. LUNSUMIO may cause the following low blood cell counts:
  • low white blood cell counts (neutropenia). Low white blood cells can increase your risk for infection
  • low red blood cell counts (anemia). Low red blood cells can cause tiredness and shortness of breath
  • low platelet counts (thrombocytopenia). Low platelet counts can cause bruising or bleeding problems

• Growth in your tumor or worsening of tumor related problems (Tumor flare). LUNSUMIO may cause serious or severe worsening of your tumor. Tell your healthcare provider if you develop any of these signs or symptoms of tumor flare during your treatment with LUNSUMIO: tender or swollen lymph nodes, chest pain, cough, trouble breathing, and pain or swelling at the site of the tumor

Your healthcare provider may temporarily stop or permanently stop treatment with LUNSUMIO if you develop severe side effects.

The most common side effects of LUNSUMIO include: tiredness, rash, fever, and headache.

The most common severe abnormal lab test results with LUNSUMIO include: decreased phosphate, increased glucose, and increased uric acid levels.

Before receiving LUNSUMIO, tell your healthcare provider about all of your medical conditions, including if you:

• have ever had an infusion reaction after receiving LUNSUMIO
• have an infection, or have had an infection in the past which lasted a long time or keeps coming back
• have or have had Epstein-Barr Virus
• are pregnant or plan to become pregnant. LUNSUMIO may harm your unborn baby. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with LUNSUMIO
  Females who are able to become pregnant:
  • your healthcare provider should do a pregnancy test before you start treatment with LUNSUMIO
  • you should use an effective method of birth control during your treatment and for 3 months after the last dose of LUNSUMIO
• are breastfeeding or plan to breastfeed. It is not known if LUNSUMIO passes into your breast milk. Do not breastfeed during treatment and for 3 months after the last dose of LUNSUMIO

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

What should I avoid while receiving LUNSUMIO?

Do not drive, operate heavy machinery, or do other dangerous activities if you develop dizziness, confusion, tremors, sleepiness, or any other symptoms that impair consciousness until your signs and symptoms go away. These may be signs and symptoms of CRS or neurologic problems.

These are not all the possible side effects of LUNSUMIO. Talk to your healthcare provider for more information about the benefits and risks of LUNSUMIO.

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

Please see Important Safety Information, including Serious Side Effects, as well as the LUNSUMIO full Prescribing Information and Medication Guide or visit https://www.Lunsumio.com.

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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