Monday, Dec 3, 2018
New analyses from the Phase III MURANO study in previously treated chronic lymphocytic leukemia show continued benefit from fixed-duration regimen after a median follow-up of three years
Updated results from two studies in newly-diagnosed acute myeloid leukemia demonstrate Venclexta combinations continued high rates of deep remission
South San Francisco, CA -- December 3, 2018 --
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced new data from the Venclexta® (venetoclax) clinical development program, including longer-term results from the Phase III MURANO study in people with previously treated chronic lymphocytic leukemia (CLL) and updated data from two Phase Ib/II studies in people with previously untreated acute myeloid leukemia (AML) ineligible for intensive chemotherapy due to coexisting medical conditions. Data from the Venclexta clinical development program that ranges across multiple blood cancers, including CLL, AML, non-Hodgkin’s lymphoma and multiple myeloma, will be featured in more than 30 abstracts, including 12 oral presentations, at the 60th American Society of Hematology (ASH) 2018 Annual Meeting.
“We’re excited by the versatility of Venclexta in treating a range of distinct types of blood cancer, including difficult-to-treat forms with limited options,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “These data support our broad clinical development program through which we hope to discover more ways Venclexta can be used alone or in combination with other medicines to treat additional types of cancer.”
Updated Data in CLL
Two new analyses of the Phase III MURANO study in relapsed or refractory (R/R) CLL demonstrated the continued clinical benefit of Venclexta plus Rituxan® (rituximab) was sustained after patients completed the chemotherapy-free, two-year fixed-duration course of therapy.
Updated Data in AML
Updated data from the Phase Ib M14-358 and Phase I/II M14-387 studies evaluating Venclexta in combination with a hypomethylating agent or low-dose cytarabine (LDAC) in people with previously untreated AML who are ineligible for intensive chemotherapy will also be presented. These results showed that among patients who were dependent upon blood transfusions at baseline, about half were able to achieve transfusion independence (the absence of transfusions during any consecutive 56 days during the study treatment period). No unexpected safety signals were observed with Venclexta in combination with hypomethylating agents or LDAC.
Results from the two studies were presented in an oral session on Sunday, December 2 at 7:45 A.M. PST and 8:00 A.M. PST, respectively (Abstract #284 and #285).
Based on earlier results from the M14-358 and M14-387 studies, Venclexta was granted accelerated approval by the U.S. Food and Drug Administration (FDA) for the treatment of people with newly-diagnosed AML who are age 75 years or older, or for those ineligible for intensive induction chemotherapy due to coexisting medical conditions. A robust clinical development program for Venclexta in AML is ongoing, including two ongoing Phase III studies evaluating Venclexta in combination with azacitidine or with LDAC for people with previously untreated AML who are ineligible for intensive chemotherapy based on results from the M14-358 and M14-387 studies.
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.
About the MURANO study
MURANO (NCT02005471) is a Phase III open-label, international, multicenter, randomized study evaluating the efficacy and safety of Venclexta in combination with Rituxan compared to bendamustine in combination with Rituxan (BR). All treatments were of fixed duration. Following a five-week dose ramp-up schedule for Venclexta, patients on the Venclexta plus Rituxan arm received six cycles of Venclexta plus Rituxan followed by Venclexta monotherapy for up to two years total. Patients on the BR arm received six cycles of BR. The study included 389 patients with chronic lymphocytic leukemia (CLL) who had been previously treated with at least one line of therapy. Patients were randomly assigned in a 1:1 ratio to receive either Venclexta plus Rituxan or BR. The primary endpoint of the study was progression-free survival (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR) and complete response rate (with or without complete blood count recovery, CR/CRi).
About the M14-358 study
The M14-358 study (NCT02203773) is an open-label, non-randomized, Phase Ib dose escalation and expansion study evaluating the safety and efficacy of Venclexta in combination with hypomethylating agents, azacitidine or decitabine, in 115 newly-diagnosed people with AML who were 60 years or older, or ineligible to receive intensive induction chemotherapy due to coexisting medical conditions. Study endpoints included complete remission rates, transfusion independence, overall survival and safety.
About the M14-387 study
The M14-387 study (NCT02287233) is an open-label, single-arm, Phase I/II dose escalation and expansion study evaluating the safety and efficacy of Venclexta in combination with LDAC in 82 newly-diagnosed people with AML who were 60 years or older, or ineligible to receive intensive induction chemotherapy due to coexisting medical conditions. Study endpoints included complete remission rates, transfusion independence, overall survival and safety.
Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia, and in 2018, it is estimated there will be more than 20,000 new cases of CLL diagnosed 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.
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 2018, 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 standard intensive chemotherapy treatment.
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 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 research with Venclexta, which is currently being studied in clinical trials across several types of blood and other cancers.
In the U.S., Venclexta has been granted four Breakthrough Therapy Designations by the FDA: in combination with Rituxan for people with relapsed or refractory chronic lymphocytic leukemia (CLL); as a monotherapy for people with relapsed or refractory CLL with 17p deletion; in combination with hypomethylating agents (azacitidine or decitabine) for people with untreated acute myeloid leukemia (AML) ineligible for intensive chemotherapy; and in combination with low-dose cytarabine for people with untreated AML ineligible for intensive chemotherapy.
Venclexta is a prescription medicine used:
‒ 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 through 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 tumor lysis syndrome.
Before taking Venclexta, patients must tell their doctor about all of their medical conditions, including if they:
What to avoid while taking Venclexta:
Patients should not drink grapefruit juice, 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:
The most common side effects of Venclexta when used in combination with rituximab in people with CLL include low white blood cell counts; diarrhea; upper respiratory tract infection; cough; tiredness; and nausea.
The most common side effects of Venclexta when used alone in people with CLL/SLL include low white blood cell counts; diarrhea; nausea; upper respiratory tract infection; low red blood cell counts; tiredness; low platelet counts; muscle and joint pain; swelling of arms, legs, hands, and feet; and cough.
The most common side effects of Venclexta in combination with azacitidine, or decitabine, or low-dose cytarabine in people with AML include low white blood cell counts; nausea; diarrhea; low platelet counts; constipation; fever with low white blood cell counts; low red blood cell counts; infection in blood; rash; dizziness; low blood pressure; fever; swelling of arms, legs, hands, and feet; vomiting; tiredness; shortness of breath; bleeding; infection in lung; stomach (abdominal) pain; pain in muscles or back; cough; and sore throat.
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 about any side effect that bothers them or that does not go away.
Report side effects to the FDA at 1-800-FDA-1088 or http://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.
Rituxan® (rituximab) injection, for intravenous use, is indicated for the treatment of:
It is not known if Rituxan is safe and effective in children.
Important Safety Information:
Rituxan can cause serious side effects that can lead to death, including:
Patients must tell their doctor or get medical help right away about any of these symptoms during or after an infusion of Rituxan:
Patients must tell their doctor right away about worsening tiredness, or yellowing of the skin or white part of the eyes during treatment with Rituxan.
Patients must tell their doctor right away about new or worsening symptoms or if anyone close to the patient notices these symptoms:
What should patients tell their doctor before receiving Rituxan?
Before receiving Rituxan, patients should tell their doctor if they:
What are the possible side effects of Rituxan?
Rituxan can cause serious side effects, including:
TLS can happen within 12 to 24 hours after an infusion of Rituxan. The patient’s doctor may do blood tests to check for TLS. The patient’s doctor may give medicine to help prevent TLS. Patients must tell their doctor right away if they have any of the following signs or symptoms of TLS:
The patient’s doctor will stop treatment with Rituxan if they have severe, serious, or life-threatening side effects.
What are the most common side effects during treatment with Rituxan?
Other side effects include:
These are not all of the possible side effects with Rituxan.
Please see the Rituxan full Prescribing Information, including the Medication Guide, for additional Important Safety Information at www.Rituxan.com.
Report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. Report side effects to Genentech at (888) 835-2555.
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.
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.