Genentech Announces Full FDA Approval for Venclexta Combinations for Acute Myeloid Leukemia

– Approval supported by data from Phase III confirmatory trials, VIALE-A and VIALE-C –

– VIALE-A study showed Venclexta plus azacitidine significantly improved overall survival in newly diagnosed AML compared to azacitidine alone –

– Supplemental New Drug Applications approved under the FDA’s Real-Time Oncology Review pilot program and Project Orbis initiative –

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) has granted full approval of Venclexta^® (venetoclax) in combination with azacitidine, or decitabine, or low-dose cytarabine (LDAC) for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. Venclexta was previously granted provisional approval in this setting under the FDA’s accelerated approval program in November 2018. Today’s FDA approval converts Venclexta’s accelerated approval in this setting to a full approval.

“Today’s full approval is supported by the significant results that showed that Venclexta in combination with azacitidine extended overall survival for people with newly diagnosed acute myeloid leukemia who cannot tolerate intensive induction chemotherapy,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “We are very pleased that this application was reviewed under the FDA’s Real-Time Oncology Review pilot and Project Orbis initiative, helping to bring this treatment option more rapidly to patients in the United States and other countries.”

The approval is primarily based on the results of two Phase III studies, VIALE-A and VIALE-C. Results of the VIALE-A study, which were published in the New England Journal of Medicine in August 2020, showed Venclexta plus azacitidine significantly reduced the risk of death by 34% (overall survival; OS) compared to azacitidine alone (median OS=14.7 months vs. (Read more…) 9.6 months; HR=0.66; 95% CI: 0.52-0.85; p<0.001). People treated with Venclexta plus azacitidine had significantly higher rates of complete remission (CR) with 37% (95% CI: 31-43) compared to 18% (95% CI: 12-25) in people treated with azacitidine alone (p<0.001). The Venclexta plus azacitidine combination also led to higher rates of CR and CR with partial hematologic recovery (CR + CRh), with the combination showing a CR + CRh of 65% compared to 23% with azacitidine alone (p<0.001). The National Comprehensive Cancer Network (NCCN) guidelines recently recommended Venclexta plus azacitidine as a Category 1 Preferred AML treatment regimen for patients ineligible for intensive chemotherapy. The most frequent serious adverse reactions (≥5%), reported in 83% of people treated with Venclexta plus azacitidine, were low white blood cell count with fever (30%), pneumonia (22%), blood infection (excluding fungal; 19%) and bleeding (6%).

For the VIALE-C study, the approval was based on the rate and duration of CR. Twenty-seven percent (95% CI: 20-35) of people treated with Venclexta plus LDAC achieved a CR (median duration of CR (DOCR)=11.1 months) vs. 7.4% (95% CI: 2.4-16) of people treated with LDAC alone (median DOCR=8.3 months). The median OS for people treated with Venclexta plus LDAC was 7.2 months vs. 4.1 months (HR=0.75; 95% CI: 0.52-1.07; p=0.114) for people treated with LDAC alone. These OS results were not statistically significant. The most frequent serious adverse reactions (≥10%), reported in 65% of people treated with Venclexta plus LDAC, were pneumonia (17%), low white blood cell count with fever (16%), and blood infection (excluding fungal; 12%).

Updated results from additional Phase I/II studies of Venclexta in people with newly diagnosed AML were included in the FDA submissions as supporting data.

“The results of the VIALE-A study reinforce the clinically meaningful benefit of Venclexta plus azacitidine for people newly diagnosed with AML,” said Courtney DiNardo, M.D., associate professor of the Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. “Based on the results of this study, this treatment regimen represents a significant advance for older AML patients, including higher response rates, greater transfusion independence, longer durations of remission, and ultimately significantly improved overall survival compared to azacitidine alone.”

This is the second time that Venclexta has been reviewed under the FDA’s new Real-Time Oncology Review (RTOR) and Assessment Aid pilot programs. The RTOR pilot program explores a more efficient review process to ensure safe and effective treatments are available to patients as early as possible. The approval was also granted under the FDA’s recently established Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among multiple regulatory agencies worldwide. Simultaneous applications were submitted to regulators in the United States, Australia, Canada, Brazil and Switzerland under Project Orbis. Additionally, the FDA has granted five Breakthrough Therapy Designations for Venclexta, two of which are for people with previously untreated AML ineligible for intensive chemotherapy.

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.

About the VIALE-A Study

VIALE-A (NCT02993523) is a Phase III, randomized, double-blind, placebo-controlled multicenter study evaluating the efficacy and safety of Venclexta^® (venetoclax) plus azacitidine, a hypomethylating agent, compared to placebo with azacitidine, in 431 people with previously untreated acute myeloid leukemia who are ineligible for intensive chemotherapy. Two-thirds of patients (n=286) received 400 mg Venclexta daily, in combination with azacitidine, and the remaining patients (n=145) received placebo tablets in combination with azacitidine. Patients enrolled in the study had a range of mutational subtypes, including IDH1/2 and FLT3. VIALE-A met its primary and key secondary endpoints.

About the VIALE-C Study

VIALE-C (NCT03069352) is a Phase III, randomized, double-blind, placebo-controlled multicenter study evaluating the efficacy and safety of Venclexta (venetoclax) plus LDAC, compared to placebo with LDAC, in 211 people with previously untreated acute myeloid leukemia who are ineligible for intensive chemotherapy. Two-thirds of patients (n=143) received 600 mg Venclexta daily in combination with LDAC and the remaining patients (n=68) received placebo in combination with LDAC.

About AML

Acute myeloid leukemia (AML) is the most common type of aggressive leukemia in adults, which has the lowest survival rate for all types of leukemia. In 2020, it is estimated there will be nearly 20,000 new cases of AML diagnosed in the United States. Many AML patients older than age 60 are unable to tolerate intensive induction chemotherapy treatment.

About Venclexta

Venclexta is a first-in-class targeted medicine designed to selectively bind 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 United States and commercialized by AbbVie outside of the United States. Together, the companies are committed to research with Venclexta, which is currently being studied in clinical trials across several types of blood and other cancers.

In the United States, Venclexta has been granted five Breakthrough Therapy Designations by the U.S. Food and Drug Administration: one for previously untreated chronic lymphocytic leukemia (CLL), two for relapsed or refractory CLL and two for previously untreated acute myeloid leukemia.

Venclexta Indications

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

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. The patient’s doctor will do tests to check their risk of getting TLS before they start taking Venclexta. The patient will receive other medicines before starting and during treatment with Venclexta to help reduce the risk of TLS. The patient may also need to receive intravenous (IV) fluids into their vein.

The patient’s doctor will do blood tests to check for TLS when the patient first starts treatment and during treatment with Venclexta. It is important for patients to keep appointments for blood tests. Patients 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 or joint pain.

Patients should drink plenty of water during treatment with 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 the first dose on the day of the first dose of Venclexta, and each time a dose is increased.

The patient’s doctor may delay, decrease the dose, or stop treatment with Venclexta if the patient has side effects.

Certain medicines must not be taken when the patient first starts taking Venclexta and while the dose is being slowly increased because of the risk of increased TLS.

• 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 must not start new medicines during treatment with Venclexta without first talking with their doctor.

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

• Have kidney or liver problems.
• Have problems with body salts or electrolytes, such as potassium, phosphorus, or calcium.
• Have a history of high uric acid levels in the blood or gout.
• Are scheduled to receive a vaccine. Patients should not receive a “live vaccine” before, during, or after treatment with Venclexta, until the patient’s doctor tells them it is okay. If the patient is not sure about the type of immunization or vaccine, the patient 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 the patient is able to become pregnant, the patient’s doctor should do a pregnancy test before the patient starts treatment with Venclexta, and the patient should use effective birth control during treatment and for at least 30 days after the last dose of Venclexta. If the patient becomes pregnant or thinks they are pregnant, the patient should tell their doctor right away.
• Are breastfeeding or plan to breastfeed. It is not known if Venclexta passes into the patient’s breast milk. Patients should not breastfeed during treatment with Venclexta. Patients should not breastfeed during treatment and for 1 week after the last dose of Venclexta.

What to avoid while taking Venclexta:

Patients 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 counts (neutropenia). Low white blood cell counts are common with Venclexta, but can also be severe. The patient’s doctor will do blood tests to check their blood counts during treatment with Venclexta and may pause dosing.
• Infections. Death and serious infections such as pneumonia and blood infection (sepsis) have happened during treatment with Venclexta. The patient’s doctor will closely monitor and treat the patient right away if they have a fever or any signs of infection during treatment with Venclexta.

Patients should tell their doctor right away if they have a fever or any signs of an infection during treatment with Venclexta.

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 counts; low red blood cell counts; diarrhea; nausea; upper respiratory tract infection; cough; muscle and joint pain; tiredness; and swelling of 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.

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 call their doctor for medical advice about side effects.

Report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Report side effects to Genentech at 1-888-835-2555.

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

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About Genentech in Hematology

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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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