Genentech, a member of the Roche Group, announced today that the U.S. Food and Drug Administration (FDA) granted accelerated approval to Venclexta™ (venetoclax) for the treatment of people with chronic lymphocytic leukemia (CLL) with 17p deletion, as detected by an FDA approved test, who have received at least one prior therapy. The pivotal study showed a clinically meaningful improvement (overall response rate, ORR) in 80.2 percent of people (95 percent CI 71.3-87.3). Venclexta is the first approved medicine designed to help restore a process in which cells self-destruct (apoptosis) by selectively blocking the BCL-2 protein and is Genentech’s tenth new medicine approved in the past seven years. 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.
"Up to half of people whose CLL progressed have 17p deletion, a genetic marker that makes the disease difficult-to-treat," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "Venclexta is the first approved medicine designed to trigger a natural process that helps cells self-destruct, and is a new way to help people who have been previously treated and have this high-risk form of the disease."
Possible serious side effects with Venclexta include pneumonia, low white blood cell count with fever, fever, abnormal immune response that results in low red blood cell count, low red blood cell count and tumor lysis syndrome (TLS). The most common side effects of Venclexta include low white blood cell count, diarrhea, nausea, low red blood cell count, upper respiratory tract infection, low platelet count and tiredness.
The FDA's Accelerated Approval Program allows conditional approval of a medicine that fills an unmet medical need for a serious condition based on early evidence suggesting clinical benefit. This indication is approved under accelerated approval based on ORR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Venclexta will be available to people in the United States within approximately one week. For those who qualify, Genentech and AbbVie plan to offer patient assistance programs for people taking Venclexta.
Venclexta was granted Breakthrough Therapy Designation by the FDA for the treatment of people with previously treated (relapsed or refractory) CLL with 17p deletion. Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases and to help ensure people have access to them through FDA approval as soon as possible. The New Drug Application for Venclexta was granted Priority Review, a designation for medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease.
A Marketing Authorization Application (MAA) has also been validated by the European Medicines Agency (EMA).
About the M13-982 Study
M13-982 (NCT01889186) is a Phase II, open-label, single arm, multicenter study evaluating the safety and efficacy of Venclexta (400 mg orally once daily following a weekly ramp-up schedule for the first five weeks) in patients with relapsed, refractory or previously untreated chronic lymphocytic leukemia (CLL) with 17p deletion. The study included 106 patients with relapsed or refractory disease with 17p deletion. In the study, 17p deletion was confirmed in blood samples from patients using the Vysis CLL FISH Probe Kit, which is FDA-approved for selection of patients for Venclexta treatment. The primary endpoint of the study is overall response rate (ORR) as determined by an independent review committee (IRC), and secondary endpoints include complete response (CR), partial response (PR) and duration of response (DOR). The level of minimal residual disease (MRD) in peripheral blood and bone marrow was assessed in a subset of patients. Results showed:
• The study met its primary endpoint, with an ORR of 80.2 percent with Venclexta, as assessed by IRC (95 percent CI 71.3-87.3).
• In addition, 7.5 percent of patients achieved a complete response with complete or incomplete recovery of blood counts in the bone marrow (5.7 percent CR, 1.9 percent CRi, respectively).
• Median DOR has not been reached with approximately 12 months median follow-up (DOR range: 2.9 to more than 19.0 months).
• MRD was evaluated in the blood and bone marrow for those who achieved a CR or CRi following treatment with Venclexta. Three percent (3/106) were MRD-negative, meaning no cancer could be detected using a specific test.
A pooled safety analysis of 240 patients with previously treated CLL from three clinical trials showed serious side effects were reported in 43.8 percent of patients. The most frequent serious side effects (occurring in at least 2 percent of patients) were pneumonia, low white blood cell count with fever, fever, abnormal immune response that results in low red blood cell count, low red blood cell count and tumor lysis syndrome (TLS). The most common Grade 3 or 4 side effects were low white blood cell count (41 percent), low red blood cell count (18 percent) and low platelet count (15 percent).
About Chronic Lymphocytic Leukemia (CLL)
CLL is the most common type of adult leukemia, and in 2016, there will be an estimated 4,660 deaths from the disease in the United States. Although signs of CLL may disappear for a period of time after initial treatment, the disease is considered incurable and many people will require additional treatment due to the return of cancerous cells.
In certain cases of CLL, a part of chromosome 17 is lost and along with it an important gene that controls apoptosis (programmed cell death) called p53. The 17p deletion is found in 3 to 10 percent of previously untreated cases and up to 30 to 50 percent of relapsed or refractory cases.
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Venclexta is a small molecule designed to selectively bind and inhibit the BCL-2 protein, which plays an important role in a process called apoptosis (programmed cell death). Overexpression of the BCL-2 protein in chronic lymphocytic leukemia (CLL) has been associated with resistance to certain therapies. It is believed that blocking BCL-2 may restore the signaling system that tells cells, including cancer cells, to self-destruct. Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group.
Together, the companies are committed to research with Venclexta, which is currently being evaluated in Phase III clinical trials for the treatment of relapsed, refractory and previously untreated CLL, along with studies in several other cancers. Venclexta is jointly commercialized by the companies in the United States and commercialized by AbbVie outside of the United States.
Venclexta™ (venetoclax) is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy.
This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Important Safety Information
Strong CYP3A inhibitors, a certain type of medicine, must not be taken when patients first start taking Venclexta and while their dose is being slowly increased.
Patients must tell their doctor right away about any side effects they experience.
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. A patient’s doctor will do tests for TLS. It is important for patients taking Venclexta to keep their appointments for blood tests. Patients will receive other medicines before starting and during treatment with Venclexta to help reduce their risk of TLS. Patients may also need to receive intravenous (IV) fluids into their vein. Patients taking Venclexta 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 pain or joint pain.
Patients should drink plenty of water when taking 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 their first dose, on the day of their first dose of Venclexta, and each time the dose is increased.
Certain medicines must not be taken when patients first start taking Venclexta and while their dose is being slowly increased.
• 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 should not start new medicines during treatment with Venclexta without first talking with their doctor.
Before taking Venclexta, patients should tell their doctor about all of their medical conditions, including if they:
• Have any kidney or liver problems.
• Have problems with their body salts or electrolytes, such as potassium, phosphorus, or calcium.
• Have a history of high uric acid levels in their blood or gout.
• Are scheduled to receive a vaccine. Patients should not receive a “live vaccine” during or after treatment with Venclexta.
• Are pregnant or plan to become pregnant. Venclexta may harm an unborn baby. If a patient is able to become pregnant, the doctor should do a pregnancy test before they start treatment with Venclexta, and they 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 breast milk. Patients should not breastfeed during treatment with Venclexta.
Patients taking Venclexta 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 Count (neutropenia): Low white blood cell counts are common with Venclexta, but can also be severe. A doctor will do blood tests to check a patient’s blood counts during treatment with Venclexta. Patients should tell their doctor right away if they have a fever or any signs of an infection.
The most common side effects of Venclexta include diarrhea, nausea, low red blood cell count, upper respiratory tract infection, low platelet count, and feeling tired.
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 tell their doctor if they have any side effect that bothers them or that does not go away.
Report side effects to the FDA at (800) FDA-1088 or fda.gov/medwatch. Patients and caregivers may also report side effects to Genentech at (888) 835-2555.
Please see additional Important Safety Information in full Prescribing Information, including Patient Information.
About Genentech In Hematology
For more than 20 years, Genentech (gene.com/hematology) 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. In addition to approved medicines, Genentech’s pipeline of investigational hematology medicines includes an anti-PDL1 antibody (atezolizumab/MPDL3280A), an anti-CD79b antibody drug conjugate (polatuzumab vedotin/RG7596) and a small molecule antagonist of MDM2 (idasanutlin/RG7388). Genentech’s dedication to developing novel molecules in hematology expands beyond oncology, with the development of the investigational hemophilia A treatment emicizumab (ACE910).
Founded 40 years ago, Genentech (gene.com) is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California.