FDA Approves Genentech’s Venclexta® Plus Acalabrutinib Combination Regimen for Previously Untreated Chronic Lymphocytic Leukemia

– First and only all-oral, fixed-duration regimen designed to provide CLL patients with the potential to experience time off treatment –

– Approval expands Genentech’s fixed-duration portfolio by providing eligible first-line patients another option alongside the established Venclexta plus Gazyva regimen –

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 the combination regimen of Venclexta^® (venetoclax) plus acalabrutinib for the treatment of previously untreated adults with chronic lymphocytic leukemia (CLL), based on results from the Phase III AMPLIFY study.

“Today’s approval represents an important step forward for people newly diagnosed with chronic lymphocytic leukemia,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “As the first and only all-oral, fixed-duration regimen, this approval gives patients the opportunity to spend more time off therapy. This milestone underscores the ongoing evolution of Venclexta-based approaches, offering clinicians another way to individualize first-line care.”

The approval of Venclexta in combination with acalabrutinib is based on results from the Phase III AMPLIFY study. The study demonstrated that Venclexta plus acalabrutinib was superior to chemoimmunotherapy. Study results showed the combination regimen reduced the risk of disease progression or death by 35% versus chemoimmunotherapy (HR 0.65; 95% CI: 0.49-0.87; p=0.0038). At a median follow-up of 42.6 months, median progression-free survival was not reached for the combination regimen (95% CI: 51.1 months, not reached) versus 47.6 months (95% CI: 43.3 months, not reached) for chemoimmunotherapy. The safety profile of Venclexta plus acalabrutinib is consistent with the known safety profile of each individual therapy alone. In chronic lymphocytic leukemia or small lymphocytic lymphoma, the most common adverse reactions (≥20%) for Venclexta when given in combination with acalabrutinib were neutropenia, headache, diarrhea, musculoskeletal pain, and COVID-19. The most common serious adverse reactions (≥2%) in patients receiving Venclexta plus acalabrutinib were COVID-19, including COVID-19 pneumonia (9%), second primary malignancies (2.7%), and neutropenia (2.1%).

CLL is one of the most common forms of leukemia in adults. While outcomes have improved in recent years, patients often face long treatment durations and ongoing disease management challenges.

“Fixed-duration regimens are a critical component of today’s chronic lymphocytic leukemia management,” said Dr. John M. Burke, M.D., Hematology and Oncology, Rocky Mountain Cancer Centers. “Having an all-oral option with a defined end date can provide patients with a clear and predictable treatment timeline. This approval provides an important new option for eligible patients to achieve durable responses in the first line.”

Genentech is committed to helping patients get the medicine their doctor prescribed. For people who qualify, Genentech offers patient support services. For more information, please call 866-4ACCESS/866-422-2377 or http://www.Genentech-Access.com.

About the AMPLIFY study

The AMPLIFY study (NCT05197192) is an AstraZeneca-sponsored global, multi-center, open-label, Phase III study evaluating fixed-duration Venclexta^® (venetoclax) plus acalabrutinib, alone or combined with Gazyva^® (obinutuzumab), compared to investigator’s choice of chemoimmunotherapy in patients with previously untreated chronic lymphocytic leukemia (CLL) without 17p deletion or TP53 mutation. In AMPLIFY, patients were randomized 1:1:1 to receive either Venclexta plus acalabrutinib, Venclexta plus acalabrutinib with Gazyva for a fixed duration, or chemoimmunotherapy. Both investigational arms using Venclexta plus acalabrutinib were administered for a fixed-duration of 14 cycles, each consisting of 28 days, while chemoimmunotherapy was administered for six cycles according to regimens. Interim results show the regimen significantly improved progression-free survival versus chemoimmunotherapy.

About CLL

Chronic lymphocytic leukemia (CLL) is a slow-growing cancer in the blood and bone marrow. It is the most common type of leukemia in the U.S., with an estimated number of 22,760 new cases of CLL in 2026. Although signs of CLL may disappear for a while after initial treatment, many people require additional treatment due to the return of cancerous cells.

About Venclexta^® (venetoclax)

Venclexta is a first-in-class targeted medicine designed to bind selectively and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumors, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta blocks the BCL-2 protein and works to help restore the process of apoptosis.

Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the U.S. and commercialized by AbbVie outside of the U.S. Together, the companies are committed to BCL-2 research and to studying Venclexta in clinical trials across several types of blood cancers. Venclexta is approved in more than 80 countries, including the U.S.

Indication

VENCLEXTA is a prescription medicine used:

• to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
• in combination with azacitidine, or decitabine, or low-dose cytarabine to treat adults with newly diagnosed acute myeloid leukemia (AML) who:
  • are 75 years of age or older, or
  • have other medical conditions that prevent the use of standard chemotherapy.

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

Important Safety Information

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

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. Your healthcare provider will do tests to check your risk of getting TLS before you start taking VENCLEXTA. You will receive other medicines before starting and during treatment with VENCLEXTA to help reduce your risk of TLS.

You may also need to receive intravenous (IV) fluids into your vein. Your healthcare provider will do blood tests to check for TLS when you first start and during treatment with VENCLEXTA. It is important to keep your appointments for blood tests. Tell your healthcare provider right away if you get 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 or joint pain.

Drink plenty of water during treatment with VENCLEXTA to help reduce your risk of getting TLS. Drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before your first dose, on the day of your first dose of VENCLEXTA, and each time your dose is increased.

Your healthcare provider may delay, decrease your dose, or stop treatment with VENCLEXTA if you get symptoms of TLS. When restarting VENCLEXTA after stopping for 1 week or longer, your healthcare provider may check again for your risk of TLS and change your dose.

Who should not take VENCLEXTA?

Patients taking certain medicines during the beginning of VENCLEXTA (when the dose is being slowly increased) are at increased risk of TLS.

• Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. VENCLEXTA and other medicines may affect each other causing serious side effects.
• Do not start new medicines during treatment with VENCLEXTA without first talking with your healthcare provider.

Before taking VENCLEXTA, tell your healthcare provider about all of your medical conditions, including if you:

• have kidney or liver problems.
• have problems with your body salts or electrolytes, such as potassium, phosphorus, or calcium.
• have a history of high uric acid levels in your blood or gout.
• are scheduled to receive a vaccine. You should not receive a “live vaccine” before, during, or after treatment with VENCLEXTA, until your healthcare provider tells you it is okay. If you are not sure about the type of immunization or vaccine, ask your healthcare provider. 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 your unborn baby.

Females who are able to become pregnant:

• Your healthcare provider should do a pregnancy test before you start treatment with VENCLEXTA.
• Use effective birth control during treatment and for 30 days after the last dose of VENCLEXTA.
• If you become pregnant or think you are pregnant, tell your healthcare provider right away.
  

• are breastfeeding or plan to breastfeed. It is not known if VENCLEXTA passes into your breast milk. Do not breastfeed during treatment with VENCLEXTA and for 1 week after the last dose.

What should I avoid while taking VENCLEXTA?

You should not drink grapefruit juice or eat grapefruit, Seville oranges (often used in marmalades), or starfruit during treatment with VENCLEXTA. These products may increase the amount of VENCLEXTA in your blood.

What are the possible side effects of VENCLEXTA?

VENCLEXTA can cause serious side effects, including:

• Low white blood cell counts (neutropenia). Your healthcare provider will do blood tests to check your blood count during treatment with VENCLEXTA and may pause dosing of VENCLEXTA or give you medicines to help treat your neutropenia if it is severe.
• Infections. Death and serious infections such as pneumonia and blood infection (sepsis) have happened during treatment with VENCLEXTA. Your healthcare provider will closely monitor and treat you right away if you get a fever or any signs of infection during treatment with VENCLEXTA.

Tell your healthcare provider right away if you get a fever or any signs of an infection during treatment with VENCLEXTA.

The most common side effects of VENCLEXTA when used in combination with acalabrutinib in people with CLL or SLL include low white blood cell count, headache, diarrhea, muscle and bone pain, and COVID-19.

The most common side effects of VENCLEXTA when used in combination with obinutuzumab or rituximab or alone in people with CLL or SLL include low white blood cell count; low platelet count; low red blood cell count; diarrhea; nausea; upper respiratory tract infection; cough; muscle and joint pain; tiredness; and swelling of your arms, legs, hands, and feet.

The most common side effects of VENCLEXTA in combination with azacitidine or decitabine or low-dose cytarabine in people with AML include nausea; diarrhea; low platelet count; constipation; low white blood cell count; fever with low white blood cell count; tiredness; vomiting; swelling of arms, legs, hands, or feet; fever; infection in lungs; shortness of breath; bleeding; low red blood cell count; rash; stomach (abdominal) pain; infection in your blood; muscle and joint pain; dizziness; cough; sore throat; and low blood pressure.

Your healthcare provider may temporarily stop VENCLEXTA treatment, decrease your dose, or completely stop treatment if you get severe side effects.

VENCLEXTA may cause fertility problems in males. This may affect your ability to father a child. Talk to your healthcare provider if you have concerns about fertility.

These are not all the possible side effects of VENCLEXTA. Call your doctor for medical advice about side effects.

You are encouraged to report side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

If you cannot afford your medication, contact genentech-access.com/patient/brands/venclexta for assistance.

About Gazyva

Gazyva^® (obinutuzumab) is a humanized monoclonal antibody designed with a Type II anti-CD20 region, for direct B cell death and a glycoengineered Fc region, for higher binding affinity and increased antibody-dependent cellular cytotoxicity (ADCC). CD20 is a protein found on certain types of B cells. Gazyva is approved in 100 countries for various types of hematological cancers.

Indication

GAZYVA^® (obinutuzumab) is a prescription medicine used with the chemotherapy drug, chlorambucil, to treat chronic lymphocytic leukemia (CLL) in adults who have not had previous CLL treatment.

Important Safety Information

What is the most important safety information I should know about GAZYVA?

Tell your doctor right away about any side effect you experience. GAZYVA can cause side effects that can become serious or life-threatening, including:

• Hepatitis B Virus (HBV): Hepatitis B can cause liver failure and death. If you have a history of hepatitis B infection, GAZYVA could cause it to return. You should not receive GAZYVA if you have active hepatitis B liver disease. Your doctor or healthcare team will need to screen you for hepatitis B before, and monitor you during and after, your treatment with GAZYVA. Sometimes this will require treatment for hepatitis B. Symptoms of hepatitis include: worsening of fatigue and yellow discoloration of skin or eyes
• Progressive Multifocal Leukoencephalopathy (PML): PML is a rare and serious brain infection caused by a virus. PML can be fatal. Your weakened immune system could put you at risk. Your doctor will watch for symptoms. Symptoms of PML include: confusion, difficulty talking or walking, dizziness or loss of balance, and vision problems

Who should not receive GAZYVA?

• Do NOT receive GAZYVA if you have had an allergic reaction (e.g., anaphylaxis or serum sickness) to GAZYVA. Tell your healthcare provider if you have had an allergic reaction to obinutuzumab or any other ingredients in GAZYVA in the past

What are the additional possible serious side effects of GAZYVA?

Tell your doctor right away about any side effects you experience. GAZYVA can cause side effects that may become severe or life-threatening, including:

• Infusion-Related Reactions (IRRs): These side effects may occur during or within 24 hours of any GAZYVA infusion. Some IRRs can be serious, including, but not limited to, severe allergic reactions (anaphylaxis), acute life-threatening breathing problems, or other life-threatening IRRs. If you have a reaction, the infusion is either slowed or stopped until your symptoms are resolved. Most patients are able to complete infusions and receive medication again. However, if the IRR is life-threatening, the infusion of GAZYVA will be permanently stopped. Your healthcare team will take steps to help lessen any side effects you may have to the infusion process. You may be given medicines to take before each GAZYVA treatment. Symptoms of IRRs may include: fast heartbeat, tiredness, dizziness, headache, redness of the face, nausea, chills, fever, vomiting, diarrhea, rash, high blood pressure, low blood pressure, difficulty breathing, and chest discomfort
• Hypersensitivity Reactions Including Serum Sickness: Some people receiving GAZYVA may have severe or life-threatening allergic reactions. This reaction may be severe, may happen during or after an infusion, and may affect many areas of the body. If an allergic reaction occurs, your doctor will stop the infusion and permanently discontinue GAZYVA
• Tumor Lysis Syndrome (TLS): Tumor lysis syndrome, including fatal cases, has been reported in patients receiving GAZYVA. GAZYVA works to break down cancer cells quickly. As cancer cells break apart, their contents are released into the blood. These contents may cause damage to organs and the heart and may lead to kidney failure requiring the need for dialysis treatment. Your doctor may prescribe medication to help prevent TLS. Your doctor will also conduct regular blood tests to check for TLS. Symptoms of TLS may include nausea, vomiting, diarrhea, and tiredness
• Serious, Including Fatal, Infections: While you’re taking GAZYVA, you may develop infections. Some of these infections may be fatal and severe, so be sure to talk to your doctor if you think you have an infection. Patients with a history of recurring or chronic infections may be at an increased risk of infection. Patients with an active infection should not be treated with GAZYVA. If you develop a serious infection, your doctor will immediately discontinue GAZYVA and begin treatment for the infection
• Low White Blood Cell Count: When you have an abnormally low count of infection-fighting white blood cells, it is called neutropenia. While you are taking GAZYVA, your doctor will do blood work to check your white blood cell count. Severe and life-threatening neutropenia can develop during or after treatment with GAZYVA. Some cases of neutropenia can last for more than one month. If your white blood cell count is low, your doctor may prescribe medication to help prevent infections
• Low Platelet Count: Platelets help stop bleeding or blood loss. GAZYVA may reduce the number of platelets you have in your blood; having low platelet count is called thrombocytopenia. This may affect the clotting process. While you are taking GAZYVA, your doctor will do blood work to check your platelet count. Severe and life-threatening thrombocytopenia can develop during treatment with GAZYVA. Fatal bleeding events have occurred in patients treated with GAZYVA. If your platelet count gets too low, your treatment may be delayed or reduced
• Disseminated Intravascular Coagulation (DIC): Fatal and severe DIC has been reported in people receiving GAZYVA. DIC is a rare and serious abnormal blood clotting condition that should be monitored and managed by your doctor as it can lead to uncontrollable bleeding

The most common side effects of GAZYVA in CLL were infusion-related reactions and low white blood cell counts.

What other information should I tell my doctor before receiving GAZYVA?

You should talk to your doctor about:

• Immunizations: Before receiving GAZYVA therapy, tell your healthcare provider if you have recently received or are scheduled to receive a vaccine. People who are treated with GAZYVA should not receive live vaccines
• Pregnancy: Tell your doctor if you are pregnant, think that you might be pregnant, or plan to become pregnant. GAZYVA may harm your unborn baby. Speak to your doctor about using GAZYVA while you are pregnant. Talk to your doctor or your child’s doctor about the safety and timing of live virus vaccinations to your infant if you received GAZYVA during pregnancy. Women of childbearing potential should use effective contraception while taking GAZYVA and for 6 months after your GAZYVA treatment
• Breastfeeding: Because of the potential risk of serious side reactions in breastfed children, women should not breastfeed while taking GAZYVA and for 6 months after your last dose

Tell your doctor about any side effects.

These are not all of the possible side effects of GAZYVA. For more information, ask your doctor or pharmacist.

GAZYVA is available by prescription only.

You may report side effects to the FDA at (800) FDA-1088, or www.fda.gov/medwatch.

You may also report side effects to Genentech at (888) 835-2555.

Please visit https://www.GAZYVA.com for the accompanying full Prescribing Information, including BOXED WARNINGS, for additional Important Safety Information.

About Genentech Access Solutions

Access Solutions is part of Genentech’s commitment to helping people access the Genentech medicines they are prescribed, regardless of their ability to pay. The team of in-house specialists at Access Solutions is dedicated to helping people navigate the access and reimbursement process and to providing assistance to eligible patients in the United States who are uninsured or cannot afford the out-of-pocket costs for their medicine. Genentech Access Solutions has provided access and reimbursement support for over 3.7 million eligible patients. Please contact Access Solutions (866) 4ACCESS/(866) 422-2377 or visit http://www.Genentech-Access.com for more information.

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 50 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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