NORTH CHICAGO, Ill.,?June 12, 2021?/PRNewswire/ -- AbbVie (NYSE: ABBV) today announced new data from the Phase 3 GLOW study comparing the efficacy and safety of the combination of IMBRUVICA^??(ibrutinib) plus VENCLEXTA^?/VENCLYXTO^??(venetoclax) (I+V) versus chlorambucil plus obinutuzumab (C+O) for first-line treatment in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had active disease requiring treatment per the International Workshop on CLL (iwCLL) criteria. The study met its primary endpoint of superior progression-free survival (PFS) as assessed by an independent review committee (IRC) with a HR 0.216 (95% CI, 0.131-0.357; p < 0.0001), demonstrating a reduction in the risk of disease progression or death for I+V of approximately 78% compared to C+O. I+V is the first all-oral, once-daily, chemotherapy-free, fixed-duration investigational combination. Results of the study will be presented at the European Hematology Association (EHA) 2021 Virtual Congress (Abstract #LB1902) during late-breaking abstract session on June 12 from 4:00-5:30 p.m. CEST. The PFS benefit with I+V was consistent across pre-specified subgroups, including patients 65 years and older and those with comorbidities (CIRS >6). The median PFS for C+O was 21 months while the median PFS for I+V had not been reached at the time of analysis. The safety profile of I+V was generally consistent with the safety profile of the single agents and tolerability profiles were consistent with CLL treatment in the enrolled patient population. "With CLL being one of the most common types of blood cancer, the expansion of research into additional treatment options for patients is an important clinical undertaking," said?Arnon Kater, M.D., Ph.D., deputy head of hematology, University of Amsterdam Faculty of Medicine. "The progression-free survival findings of ibrutinib and venetoclax in the GLOW study are promising and show the potential to become an additional treatment option for people living with CLL." Secondary endpoints included rates of undetectable minimal residual disease (uMRD), complete response rate (CR) and overall response rate (ORR). The rate of uMRD in the bone marrow as assessed by next generation sequencing was significantly higher for patients treated with I+V compared to those treated with C+O (p<0.0001). Three months after the completion of treatment uMRD was observed in 51.9% and 17.1%, respectively. Peripheral blood (PB) uMRD persisted 12 months after end of treatment in 49% with I+V and 12% with C+O. The CR rate was also significantly higher with I+V vs. C+O (38.7% vs. 11.4%) (p < 0.0001). The ORR was not significantly different between I+V and C+O treated groups. Time to subsequent therapy was longer for I+V (HR 0.143, 95% CI 0.05-0.41). "We are encouraged by these results, which further support the efficacy of these two well-established therapies," said?Mohamed Zaki, M.D., Ph.D., vice president and head, global oncology development, AbbVie. "We remain steadfast in our commitment to continue the research and development of this combination as a potential treatment for CLL with the ultimate goal to put patients into remission with a fixed-duration, oral therapy."   The safety profile of I+V was generally consistent with the safety profile of the single agents and tolerability profiles were consistent with CLL treatment in the enrolled patient population. Most common grade =3 treatment-emergent adverse events (AEs) were neutropenia (34.9%), infections (17%), and diarrhea (10.4%) for I+V; neutropenia (49.5%), infections (11.4%), and thrombocytopenia (20%) for C+O. At time of analysis, overall survival was immature; there were eleven deaths in the fixed-duration I+V arm and twelve in the C+O arm. Deaths during treatment occurred in seven patients on I+V and two patients on C+O.   Results from the ongoing Phase 2 CAPTIVATE study, assessing the I+V combination for first-line treatment of patients with CLL or SLL (PCYC-1142), were presented at the 2021 American Society of Clinical Oncology Annual Meeting (Abstract #7501) and the EHA 2021 Virtual?Congress. About CLL CLL is one of the two most common forms of leukemia in adults and is a type of cancer that can develop from cells in the bone marrow that later mature into certain white blood cells (called lymphocytes).?While these cancer cells start in the bone marrow, they later spread into the blood. There are approximately 195,129 people with CLL living in?the United States?with more than 21,000 newly diagnosed patients in 2021.^1,2?CLL is predominately a disease of the elderly, with a median age at diagnosis of 70 years and is more common among men than women.³ About the GLOW Study
The GLOW study is a randomized, open label Phase 3 trial comparing progression-free survival in patients treated with either I+V or C+O as assessed by an Independent Review Committee. It enrolled patients (pts) aged =65 years or 18-64 years with cumulative illness rating scale score >6 or creatinine clearance <70 mL/min who had active disease requiring treatment per the International Workshop on CLL (iwCLL) criteria. Patients with del(17p) or known TP53?mutations were excluded.?There were 211 patients randomly assigned in a 1:1 ratio to receive either I+V (106) and or C+O (105) and the median age was 71 years. Patients assigned to I+V received treatment for 15 cycles (1 cycle is 28 days), starting with three cycles of ibrutinib monotherapy lead-in followed by the combination of I+V for 12 cycles. Patients assigned to C+O were treated for six cycles. About?IMBRUVICA^??(Ibrutinib) IMBRUVICA^??(ibrutinib) is a once-daily, first-in-class BTK inhibitor that is administered orally, and is jointly developed and commercialized by Pharmacyclics, LLC, an AbbVie Company, and Janssen Biotech, Inc. (Janssen). The BTK protein sends important signals that tell B cells to mature and produce antibodies. BTK signaling is needed by specific cancer cells to multiply and spread.^4,5?By blocking BTK, IMBRUVICA may help move abnormal B cells out of their nourishing environments in the lymph nodes, bone marrow, and other organs.⁶ Since its launch in 2013, IMBRUVICA?has received 11 FDA approvals across six disease areas: chronic lymphocytic leukemia (CLL) with or without 17p deletion (del17p); small lymphocytic lymphoma (SLL) with or without del17p; Waldenstr?m macroglobulinemia; previously-treated patients with mantle cell lymphoma (MCL)*; previously-treated patients with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy* ? and previously-treated patients with chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy.⁷ IMBRUVICA?is now approved in more than 100 countries and has been used to treat more than 230,000 patients worldwide across its approved indications. IMBRUVICA?is the only FDA-approved medicine in WM and cGVHD. IMBRUVICA?has been granted four Breakthrough Therapy Designations from the U.S. FDA. This designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases. IMBRUVICA?was one of the first medicines to receive FDA approval via the Breakthrough Therapy Designation pathway. Since 2019, the National Comprehensive Cancer Network^??(NCCN^?), a not-for-profit alliance of 28 leading cancer centers devoted to patient care, research, and education, recommends ibrutinib (IMBRUVICA^?) as a preferred regimen for the initial treatment of CLL/SLL and has Category 1 treatment status for treatment-na?ve patients without deletion 17p. Since January 2020, the NCCN Guidelines^??have categorized IMBRUVICA with or without rituximab as a preferred regimen for the treatment of relapsed/refractory MCL. As of?September 2020, the NCCN guidelines were updated to reflect IMBRUVICA?with or without rituximab as the only Category 1 preferred regimen for both untreated and previously treated WM patients. IMBRUVICA?is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA?is the most comprehensively studied BTK inhibitor, with more than 150 ongoing clinical trials. There are approximately 30 ongoing company-sponsored trials, 14 of which are in Phase 3, and more than 100 investigator-sponsored trials and external collaborations that are active around the world. For more information, visit?www.IMBRUVICA.com *Accelerated approval was granted for the MCL and MZL indications based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials. About VENCLEXTA^?/VENCLYXTO^??(venetoclax) VENCLEXTA^?/VENCLYXTO^??(venetoclax) is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers, BCL-2 prevents cancer cells from undergoing their natural death or self-destruction process, called apoptosis. VENCLXEXTA/VENCLYXTO targets the BCL-2 protein and works to help restore the process of apoptosis. VENCLEXTA/VENCLYXTO 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. Together, the companies are committed to BCL-2 research and to studying venetoclax in clinical trials across several blood cancers. Venetoclax is approved in more than 80 countries, including the U.S. IMPORTANT SAFETY INFORMATION US IMBRUVICA^??Important Side Effect Information^7? Before taking IMBRUVICA^?, tell your healthcare provider about all of your medical conditions, including if you:

• have had recent surgery or plan to have surgery. Your healthcare provider may stop IMBRUVICA^??for any planned medical, surgical, or dental procedure.
• have bleeding problems.
• have or had heart rhythm problems, smoke, or have a medical condition that increases your risk of heart disease, such as high blood pressure, high cholesterol, or diabetes.
• have an infection.
• have liver problems.
• are pregnant or plan to become pregnant. IMBRUVICA^??can harm your unborn baby. If you are able to become pregnant, your healthcare provider will do a pregnancy test before starting treatment with IMBRUVICA^?. Tell your healthcare provider if you are pregnant or think you may be pregnant during treatment with IMBRUVICA^?.
  • Females?who are able to become pregnant should use effective birth control (contraception) during treatment with IMBRUVICA^??and for 1 month after the last dose.
  • Males?with female partners who are able to become pregnant should use effective birth control, such as condoms, during treatment with IMBRUVICA^??and for 1 month after the last dose.
• are breastfeeding or plan to breastfeed. Do not breastfeed during treatment with IMBRUVICA^??and for 1 week after the last dose.

Tell your healthcare provider about all the medicines you take,?including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking IMBRUVICA^??with certain other medicines may affect how IMBRUVICA^??works and can cause side effects. How should I take IMBRUVICA^??

• Take IMBRUVICA^??exactly as your healthcare provider tells you to take it.
• Take IMBRUVICA^??1 time a day.
• Swallow IMBRUVICA^??capsules or tablets whole with a glass of water.
• Do not open, break or chew IMBRUVICA^??capsules.
• Do not cut, crush or chew IMBRUVICA^??tablets.
• Take IMBRUVICA^??at about the same time each day.
• If you miss a dose of IMBRUVICA^??take it as soon as you remember on the same day. Take your next dose of IMBRUVICA^??at your regular time on the next day. Do not take extra doses of IMBRUVICA^??to make up for a missed dose.
• If you take too much IMBRUVICA^??call your healthcare provider or go to the nearest hospital emergency room right away.

What should I avoid while taking IMBRUVICA^??

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

What are the possible side effects of IMBRUVICA^?? IMBRUVICA^??may cause serious side effects, including:

• Bleeding problems (hemorrhage)?are common?during treatment with IMBRUVICA^?, and can also be serious and may lead to death. Your risk of bleeding may increase if you are also taking a blood thinner medicine. Tell your healthcare provider if you have any signs of bleeding, including: blood in your stools or black stools (looks like tar), pink or brown urine, unexpected bleeding, or bleeding that is severe or that you cannot control, vomit blood or vomit looks like coffee grounds, cough up blood or blood clots, increased bruising, dizziness, weakness, confusion, change in your speech, or a headache that lasts a long time or severe headache.
• Infections?can happen during treatment with IMBRUVICA^?.?These infections can be serious and may lead to death. Tell your healthcare provider right away if you have fever, chills, weakness, confusion, or other signs or symptoms of an infection during treatment with IMBRUVICA^?.
• Decrease in blood cell counts.?Decreased blood counts (white blood cells, platelets, and red blood cells) are common with IMBRUVICA^?, but can also be severe. Your healthcare provider should do monthly blood tests to check your blood counts.
• Heart problems.?Serious heart rhythm problems (ventricular arrhythmias, atrial fibrillation, and atrial flutter), heart failure, and death have happened in people treated with IMBRUVICA^?, especially in people who have an increased risk for heart disease, have an infection, or who have had heart rhythm problems in the past. Tell your healthcare provider if you get any symptoms of heart problems, such as feeling as if your heart is beating fast and irregular, lightheadedness, dizziness, shortness of breath,?swelling of the feet, ankles, or legs, chest discomfort, or you faint.?If you develop any of these symptoms, your healthcare provider may do a test to check your heart (ECG) and may change your IMBRUVICA^??dose.
• High blood pressure (hypertension).?New or worsening high blood pressure has happened in people treated with IMBRUVICA^?. Your healthcare provider may start you on blood pressure medicine or change current medicines to treat your blood pressure.
• Second primary cancers.?New cancers have happened during treatment with IMBRUVICA^?, including cancers of the skin or other organs.
• Tumor lysis syndrome (TLS).?TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure and the need for dialysis treatment, abnormal heart rhythm, seizure, and sometimes death. Your healthcare provider may do blood tests to check you for TLS.

The most common side effects of IMBRUVICA^??in adults with B-cell malignancies (MCL, CLL/SLL, WM and MZL) include:

• diarrhea
• tiredness
• muscle and bone pain
• rash
• bruising

The most common side effects of IMBRUVICA^??in adults with?cGVHD?include:

• tiredness
• bruising
• diarrhea
• mouth sores (stomatitis)
• muscle spasms
• nausea
• pneumonia

Diarrhea is a common side effect in people who take IMBRUVICA^?. Drink plenty of fluids during treatment with IMBRUVICA^??to help reduce your risk of losing too much fluid (dehydration) due to diarrhea. Tell your healthcare provider if you have diarrhea that does not go away. These are not all the possible side effects of IMBRUVICA^?. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. General information about the safe and effective use of IMBRUVICA^?? Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use IMBRUVICA^??for a condition for which it was not prescribed. Do not give IMBRUVICA^??to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about IMBRUVICA^??that is written for health professionals. Please?click?here?for?full?Prescribing?Information. Uses of VENCLEXTA^??(venetoclax) in US 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 VENCLEXTA^??(venetoclax) US Safety Information US VENCLEXTA^??Important Safety Information⁸ 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 treatment and?during treatment with VENCLEXTA.?It is important to keep your appointments for blood tests. Tell your healthcare 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 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 have side effects.?When restarting VENCLEXTA after stopping for 1 week or longer, your healthcare provider?may again check for your risk of TLS and change your dose. 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 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. If you are able to become pregnant, your healthcare provider should do a pregnancy test before you start treatment with VENCLEXTA, and you should use effective birth control during treatment and for at least 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 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 counts (neutropenia).?Low white blood cell counts are common with VENCLEXTA, but can also be severe. Your healthcare provider will do blood tests to check your 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. Your healthcare provider will closely monitor and treat you right away if you have a fever or any signs of infection during treatment with VENCLEXTA.

Tell your healthcare provider right away if you 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 counts; low platelet counts; low red blood cell counts; 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. 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?drug?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. The full U.S. prescribing information, including Medication Guide, for VENCLEXTA^??can be found?here. Indications and Important VENCLYXTO^??(venetoclax) EU Safety Information⁹ Indication?
Venclyxto in combination with obinutuzumab is indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL). Venclyxto in combination with rituximab is indicated for the treatment of adult patients with CLL who have received at least one prior therapy. Venclyxto monotherapy is indicated for the treatment of CLL:

• In the presence of 17p deletion or?TP53?mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor, or
• In the absence of 17p deletion or?TP53?mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.

Venclyxto in combination with a hypomethylating agent is indicated for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy. Contraindications Hypersensitivity to the active substance or to any of the excipients is contraindicated.?Concomitant use of strong CYP3A inhibitors at initiation and during the dose-titration phase due to increased risk for tumour lysis syndrome (TLS). Concomitant use of preparations containing?St. John's?wort as Venclyxto efficacy may be reduced. Special Warnings & Precautions for Use Tumour Lysis syndrome, including fatal events, has occurred in patients when treated with Venclyxto. For CLL and AML, please refer to the indication-specific recommendations for prevention of TLS in the Venclyxto summary of product characteristic (SmPC). Patients should be assessed for risk and should receive appropriate prophylaxis, monitoring, and management for TLS.?The risk of TLS is a continuum based on multiple factors,