- 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
- Data will be presented during the late-breaking abstract session at the European Hematology Association (EHA) 2021 Virtual Congress (Abstract #LB1902)
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.
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; Waldenström 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-naïve 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 Information7
Before taking IMBRUVICA®, tell your healthcare provider about all of your medical conditions, including if you:
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®?
What should I avoid while taking IMBRUVICA®?
What are the possible side effects of IMBRUVICA®?
IMBRUVICA® may cause serious side effects, including:
The most common side effects of IMBRUVICA® in adults with B-cell malignancies (MCL, CLL/SLL, WM and MZL) include:
The most common side effects of IMBRUVICA® in adults with cGVHD include:
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.
Pleaseclick herefor full Prescribing Information.
Uses of VENCLEXTA® (venetoclax) in US
VENCLEXTA is a prescription medicine used:
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.
Before taking VENCLEXTA, tell your healthcare provider about all of your medical conditions,including if you:
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:
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
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:
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.
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, including comorbidities. Venclyxto poses a risk for TLS at initiation and during the dose-titration phase. Changes in electrolytes consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of Venclyxto and at each dose increase.
Neutropenia (grade 3 or 4) has been reported. Complete blood counts should be monitored throughout the treatment period.
In patients with AML, neutropenia (grade 3 or 4) is common before starting treatment. The neutrophil counts can worsen with Venetoclax in combination with a hypomethylating agent. Neutropenia can recur with subsequent cycles of therapy. Dose modification and interruptions for cytopenias are dependent on remission status.
For CLL and AML, please refer to the indication-specific recommendations for dose modifications for toxicities in the Venclyxto SmPC.
Serious infections including sepsis with fatal outcome have been reported. Monitoring of any signs and symptoms of infection is required. Suspected infections should receive prompt treatment including antimicrobials and dose interruption or reduction as appropriate.
Live vaccines should not be administered during treatment or thereafter until B-cell recovery.
In CLL and AML CYP3A inhibitors may increase Venclyxto plasma concentrations.
In CLL, at initiation and dose-titration phase, strong CYP3A inhibitors are contraindicated due to increased risk for TLS and moderate CYP3A inhibitors should be avoided. If moderate CYP3A inhibitors must be used, please refer to the recommendations for dose modifications in the Venclyxto SmPC.
In AML, please refer to the AML-specific recommendation for dose modifications for potential interactions with CYP3A inhibitors, in the Venclyxto SmPC.
Avoid concomitant use of P-gp and BCRP inhibitors at initiation and during the dose titration phase.
CYP3A4 inducers may decrease Venclyxto plasma concentrations. Avoid coadministration with strong or moderate CYP3A inducers. These agents may decrease venetoclax plasma concentrations.
Co-administration of bile acid sequestrants with VENCLYXTO is not recommended as this may reduce the absorption of VENCLYXTO.
The most commonly occurring adverse reactions (>=20%) of any grade in patients receiving venetoclax in the combination studies with obinutuzumab or rituximab were neutropenia, diarrhoea, and upper respiratory tract infection. In the monotherapy studies, the most common adverse reactions were neutropenia/neutrophil count decreased, diarrhoea, nausea, anaemia, fatigue, and upper respiratory tract infection.
The most frequently occurring serious adverse reactions (>=2%) in patients receiving venetoclax in combination with obinutuzumab or rituximab were pneumonia, sepsis, febrile neutropenia, and TLS. In the monotherapy studies, the most frequently reported serious adverse reactions (>=2%) were pneumonia and febrile neutropenia.
Discontinuations due to adverse reactions occurred in 16% of patients treated with venetoclax in combination with obinutuzumab or rituximab in the CLL14 and Murano studies, respectively. In the monotherapy studies with venetoclax, 11% of patients discontinued due to adverse reactions.
Dosage reductions due to adverse reactions occurred in 21% of patients treated with the combination of venetoclax and obinutuzumab in CLL14, in 15% of patients treated with the combination of venetoclax and rituximab in Murano, and in 14% of patients treated with venetoclax in the monotherapy studies. The most common adverse reaction that led to dose interruptions was neutropenia.
The most commonly occurring adverse reactions (>=20%) of any grade in patients receiving venetoclax in combination with azacitidine or decitabine in the VIALE-A and M14-358, respectively, were thrombocytopenia, neutropenia, febrile neutropenia, nausea, diarrhoea, vomiting, anaemia, fatigue, pneumonia, hypokalaemia, and decreased appetite, haemorrhage, dizziness/syncope, hypotension, headache, abdominal pain, and anaemia.
The most frequently reported serious adverse reactions (≥5%) in patients receiving venetoclax in combination with azacitidine were febrile neutropenia, pneumonia, sepsis and haemorrhage. In M14-358, the most frequently reported serious adverse reactions (≥5%) were febrile neutropenia, pneumonia, bacteraemia and sepsis.
Discontinuations due to adverse reactions occurred in 24% of patients treated with venetoclax in combination with azacitidine in the VIALE-A study, and 26% of patients treated with venetoclax in combination with decitabine in the M14-358 study, respectively.
Dosage reductions due to adverse reactions occurred in 2% of patients in VIALE-A, and in 6 % of patients in M14-358. Venetoclax dose interruptions due to adverse reactions occurred in 72% and 65 % of patients, respectively. The most common adverse reaction that led to dose interruption (>10%) of Venetoclax in VIALE-A, were febrile neutropenia, neutropenia, pneumonia, and thrombocytopenia. The most common adverse reactions that led to dose interruption (≥5%) of venetoclax in M14-358 were febrile neutropenia, neutropenia/neutrophil count decreased, pneumonia, platelet count decreased, and white blood cell count decreased.
Patients with reduced renal function (CrCl <80 mL/min) may require more intensive prophylaxis and monitoring to reduce the risk of TLS at initiation and during the dose-titration phase. Safety in patients with severe renal impairment (CrCl <30 mL/min) or on dialysis has not been established, and a recommended dose for these patients has not been determined.
For patients with severe (Child-Pugh C) hepatic impairment, a dose reduction of at least 50% throughout treatment is recommended.
Venclyxto may cause embryo-fetal harm when administered to a pregnant woman. Advise nursing women to discontinue breastfeeding during treatment.
This is not a complete summary of all safety information. See VENCLYXTO® full summary of product characteristics (SmPC) athttps://www.ema.europa.eu/en/documents/product-information/venclyxto-epar-product-information_en.pdf. Globally, prescribing information varies; refer to the individual country product label for complete information.
About AbbVie in Oncology
At AbbVie, we are committed to transforming standards of care for multiple blood cancers while advancing a dynamic pipeline of investigational therapies across a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potentially breakthrough medicines. We are evaluating more than 20 investigational medicines in over 300 clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit http://www.abbvie.com/oncology.
AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women's health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, Instagram, YouTube and LinkedIn.
Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, failure to realize the expected benefits from AbbVie's acquisition of Allergan plc ("Allergan"), failure to promptly and effectively integrate Allergan's businesses, competition from other products, challenges to intellectual property, difficulties inherent in the research and development process, adverse litigation or government action, changes to laws and regulations applicable to our industry and the impact of public health outbreaks, epidemics or pandemics, such as COVID-19. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2020 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.
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7 IMBRUVICA U.S. Prescribing Information.
8 VENCLEXTA (venetoclax) [Package Insert]. North Chicago, IL.: AbbVie Inc.
9 Summary of Product Characteristics for VENCLYXTO (venetoclax). Ludwigshafen, Germany: AbbVie Deutschland GmbH & Co. KG.
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