On July 12, 2018 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, reported it submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for venetoclax in combination with a hypomethylating agent (HMA) or in combination with low-dose cytarabine (LDAC) for the treatment of newly diagnosed patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy (Press release, AbbVie, JUL 12, 2018, View Source [SID1234527661]).

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The sNDA submission is based on investigational data from two studies: M14-358, a Phase 1b trial evaluating venetoclax in combination with an HMA (azacitidine or decitabine), and M14-387, a Phase 1/2 trial of venetoclax in combination with LDAC.

"AML is an especially lethal and aggressive form of blood cancer with limited advances in care in three decades and few treatment options for patients ineligible for intensive chemotherapy," said Michael Severino, M.D., executive vice president of research and development and chief scientific officer, AbbVie. "The data submitted to the FDA may potentially reshape how AML is treated. We look forward to working with the FDA and other health authorities during the review of these data."

AML, primarily a disease of older patients, is the most common form of acute leukemia in adults, in which the bone marrow makes abnormal, immature types of white blood cells, red blood cells or platelets.2,3 AML is an aggressive blood cancer that, if left untreated, can progress quickly.2 In the U.S., it is estimated there will be 19,520 new cases and 10,670 deaths due to AML in 2018.3

Approximately 27 percent of patients diagnosed with AML will survive five years or more.3 Disease recurrence occurs in most patients with AML within three years of diagnosis.1,4,5 Although few treatments are available, AML patients who are ineligible for intensive remission induction therapy may be treated with LDAC or HMAs.1,6 Only about one-third of AML patients older than age 60 are able to tolerate the intensive chemotherapy required to achieve optimal results.7 Median survival is five to 10 months in older AML patients who are ineligible for intensive chemotherapy.1

The challenges of treating AML, including in older adults, is an ongoing topic of discussion among the medical community. Daniel Pollyea, M.D., director of Leukemia Services at University of Colorado Hospital, recently reflected on his experience treating patients with AML. "We have an incredible opportunity to develop better treatment options for people with AML. Still, right now every aspect of this disease represents an unmet need," he said. For more on Dr. Pollyea’s perspective, please read "A Physicians View: Facing the Challenges of Treating AML in Older Adults."

Venetoclax, an oral B-cell lymphoma-2 (BCL-2) inhibitor, has been granted four Breakthrough Therapy Designations (BTDs) from the FDA including for the combination of venetoclax with an HMA (azacitidine or decitabine) for treatment-naïve patients with AML who are ineligible to receive standard induction therapy (high-dose chemotherapy) and for the combination of venetoclax with LDAC for treatment-naïve patients with AML who are ineligible for intensive chemotherapy. According to the FDA, BTD is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).8

If approved in AML, venetoclax would be available for use in two blood cancers, chronic lymphocytic leukemia (CLL) and AML. Venetoclax recently received expanded approval in the U.S. for use alone or in combination with rituximab for the treatment of relapsed/refractory (R/R) CLL or small lymphocytic lymphoma (SLL) patients, with or without 17p deletion, who have received at least one prior therapy.9

In addition to CLL and AML, venetoclax is being studied in a range of hematologic malignancies including multiple myeloma (MM), non-Hodgkin lymphoma (NHL) and myelodysplastic syndrome (MDS).10,11,12 Venetoclax is being developed by AbbVie and Roche and is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S. Together, the companies are committed to BCL-2 research with venetoclax, which is currently being evaluated in clinical trials in several hematologic cancers.10,11,12,13,14

Additional information regarding venetoclax clinical trials is available on www.clinicaltrials.gov.

About VENCLEXTA (venetoclax tablets) (US)

VENCLEXTA is an oral BCL-2 inhibitor that targets a specific protein in the body called BCL-2.9 When you have CLL or SLL, BCL-2 may build up and prevent cancer cells from self-destructing naturally. VENCLEXTA targets BCL-2 in order to help restore the process of apoptosis.9

VENCLEXTA is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S.

VENCLEXTA (VENCLYXTO in the EU) is currently approved as a monotherapy in 53 nations, including the U.S. AbbVie, in collaboration with Roche and Genentech, is currently working with regulatory agencies around the world to bring this medicine to additional eligible patients in need.

VENCLEXTA was first approved in April 2016 when the U.S. FDA granted accelerated approval of VENCLEXTA for the treatment of patients with CLL with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy.15 The FDA approved this indication under accelerated approval based on overall response rate.15 Based on the results of the MURANO study, VENCLEXTA was approved in June 2018 for the treatment of patients with CLL or SLL, with or without 17p deletion, who have received at least one prior therapy in combination with rituximab or as monotherapy.9

Use and Important Safety Information (US)

Use
What is VENCLEXTA (venetoclax tablets)?
VENCLEXTA is a prescription medicine used to treat people with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with or without 17p deletion, who have received at least one prior treatment.

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

Important VENCLEXTA (venetoclax tablets) 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 health care provider will do tests for TLS. It is important to keep your appointments for blood tests. 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. Tell your health care provider right away if you 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.

Drink plenty of water when taking 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.

Who should not take VENCLEXTA?
Certain medicines must not be taken when you first start taking VENCLEXTA and while your dose is being slowly increased because of the risk of increased tumor lysis syndrome.

Tell your health care 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 health care provider.
Before taking VENCLEXTA, tell your health care 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 health care provider tells you it is okay. If you are not sure about the type of immunization or vaccine, ask your health care 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. If you are able to become pregnant, your health care provider should do a pregnancy test before you start treatment with VENCLEXTA, and you 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 your breast milk. Do not breastfeed during treatment with VENCLEXTA.
What should I avoid while taking VENCLEXTA?
You should not drink grapefruit juice, eat grapefruit, Seville oranges (often used in marmalades), or starfruit while you are taking 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 count (neutropenia). Low white blood cell counts are common with VENCLEXTA but can also be severe. Your health care provider will do blood tests to check your blood counts during treatment with VENCLEXTA. Tell your health care provider right away if you have a fever or any signs of an infection.
The most common side effects of VENCLEXTA when used in combination with rituximab include low white blood cell count, diarrhea, upper respiratory tract infection, cough, tiredness, and nausea.

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

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

These are not all the possible side effects of VENCLEXTA. Tell your health care provider if you have any side effect that bothers you or that does not go away.

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

The full U.S. prescribing information, including Medication Guide, for VENCLEXTA can be found here. Globally, prescribing information varies; refer to the individual country product label for complete information.

Patient Assistance
For those who qualify, patient assistance options are available for people taking VENCLEXTA in the U.S. If people cannot afford their medication, they should contact www.pparx.org for assistance.