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NORTH CHICAGO, Ill., April 23, 2021 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for VENCLYXTO® (venetoclax) in combination with hypomethylating agents for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. The positive CHMP opinion is a scientific recommendation for marketing authorization to the European Commission (EC), which is expected to deliver its final decision on VENCLYXTO combination therapy for use in AML in the first half of 2021.
The positive CHMP opinion represents the third for an extension of indications for VENCLYXTO. The opinion is based on results from the double-blind, placebo-controlled VIALE-A (M15-656) and the Phase 1b open-label, nonrandomized, multicenter M14-358 trial.
"This positive CHMP opinion for VENCLYXTO in acute myeloid leukemia is a critical step to providing new therapeutic options in the European Union for patients with this devastating disease," said Mohamed Zaki, M.D., Ph.D., vice president and global head of oncology development at AbbVie. "Enabling improved outcomes including potentially prolonging the lives of patients with malignant diseases such as acute myeloid leukemia is part of our mission and an objective we pursue relentlessly every day."
AML is the most common acute leukemia in the world.1 An estimated 160,000 people are currently living with the disease globally. 1 The rate of new cases of acute myeloid leukemia is 4.3 per 100,000 men and women per year.3 It is also among the most difficult blood cancers to treat.2 Despite advances in available therapies and care, the five-year survival rate for patients diagnosed with AML remains approximately 29 percent.3 AML typically worsens quickly, and due to age and comorbidities, not all patients can tolerate intensive chemotherapy.4
"AML is an incredibly aggressive form of cancer, and patients who are diagnosed with this disease are often so ill that they cannot tolerate the intensive chemotherapy that healthcare providers would typically prescribe," said Hartmut Döhner, M.D., Professor of Medicine and Director, Department of Hematology, Oncology, Palliative Care, Rheumatology and Infectious Diseases at University Hospital in Ulm, Germany. "VENCLYXTO combination therapy is a promising advancement for patients and their healthcare providers facing this challenging, lethal form of cancer."
Venetoclax 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.
About the VENCLYXTO AML Clinical Trial Program AbbVie's clinical trial program to evaluate VENCLYXTO combination therapy in patients with newly diagnosed acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy included two studies conducted around the world.
VIALE-A (M15-656) Phase 3 Trial The randomized, double-blind, placebo-controlled VIALE-A (M15-656) trial evaluated the efficacy and safety of VENCLYXTO in combination with azacitidine in patients with newly diagnosed AML who were ineligible for intensive chemotherapy. The study met its primary endpoints of statistically significant improvement of overall survival (OS) and complete remission rate and complete remission with incomplete hematologic recovery (CR + CRi). OS was 14.7 months for the VENCLYXTO plus azacitidine arm versus 9.6 months in the placebo plus azacitidine arm. The study also met secondary endpoints, with the VENCLYXTO plus azacitidine arm resulting in a CR rate of 36.7 percent vs. 17.9 percent in the placebo plus azacitidine arm and a composite complete remission rate (CR + CRi) of 66.4 percent versus 28.3 percent. The safety profile of VENCLYXTO plus azacitidine was consistent with the known side-effect profiles of both agents, and adverse events (AEs) were consistent with expectations for an older AML population; no differences between the two treatment arms with respect to quality-of-life measures were seen. The most frequently reported serious AEs in the VENCLYXTO plus azacitidine arm and placebo plus azacitidine arm were febrile neutropenia (in 30 percent and 10 percent), pneumonia (in 17 percent and 22 percent), sepsis (in 6 percent and 8 percent), and haemorrhage (in 9 percent and 6 percent).5
M14-358 Phase 1b Trial The non-randomized, open-label M14-358 trial evaluated VENCLYXTO in combination with azacitidine or decitabine in patients with newly diagnosed AML. The trial showed patients treated with VENCLYXTO in combination with azacitidine achieved a CR rate of 44 percent and a CR+CRi rate of 71 percent. The median duration of response for patients treated with VENCLYXTO in combination with azacitidine who achieve a CR or CRi was 21.9 months. Median time to first CR or CRi was 1.2 months (range: 0.7 to 7.7 months). Patients who received VENCLYXTO in combination with decitabine achieved a CR rate of 55 percent and a CR+CRi rate of 74 percent. The median duration of response for patients treated with VENCLYXTO in combination with decitabine who achieved a CR or CRi was 15 months. Median time to first CR or CRi was 1.9 months (range: 0.9 to 5.4 months). The most frequently reported serious AEs in patients receiving VENCLYXTO in combination with azacitidine were febrile neutropenia (31 percent) and pneumonia (26 percent). The most frequently reported serious AEs in patients receiving VENCLYXTO in combination with decitabine were febrile neutropenia (42 percent), pneumonia (29 percent), bacteraemia (16 percent) and sepsis (6 percent).6
About VENCLYXTO® (venetoclax)
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. VENCLYXTO targets the BCL-2 protein and works to help restore the process of apoptosis.
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 and other cancers. Venetoclax is approved in more than 80 countries, including the U.S.
Indication and Important VENCLYXTO (venetoclax) EU Safety Information7
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:
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 tumor lysis syndrome (TLS). Concomitant use of preparations containing St. John's wort as VENCLYXTO efficacy may be reduced.
Special Warnings & Precautions for Use
TLS, including fatal events, has occurred in patients with CLL when treated with VENCLYXTO.
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 in the initial 5-week 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 and complete blood counts should be monitored throughout the treatment period.
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.
Drug Interactions
CYP3A inhibitors may increase VENCLYXTO plasma concentrations. 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, physicians should refer to the SmPC for dose adjustment recommendations. At steady daily dose: moderate or strong CYP3A inhibitors must be used, physicians should refer to the VENCLYXTO summary of product characteristics (SmPC) for dose adjustment recommendations.
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.
Adverse Reactions
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.
Specific Populations
Patients with reduced renal function (CrCl
