AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) has approved Venclexta (venetoclax) in combination with obinutuzumab (Gazyva®) for previously untreated patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).1 The FDA granted Breakthrough Therapy designation for this combination therapy, and early submission of the data was provided under the Real-Time Oncology Review (RTOR) pilot program, which led to approval in just over two months, following submission of the complete application.

"This FDA approval provides a new chemotherapy-free combination treatment option for patients, and underscores the growing utility of Venclexta in CLL," said Michael Severino, M.D., vice chairman and president, AbbVie.  "The approval is based on findings from the CLL14 trial in which patients received a 12-month treatment regimen. The majority of patients receiving Venclexta in the trial remained progression-free at two years."

Data from the CLL14 trial is expected to be presented at an upcoming medical meeting and published in a journal this year.

"Patients never treated for their CLL have had to rely largely on chemotherapy as their initial treatment," said Michael Hallek, M.D., lead investigator of the CLL14 study, Department of Internal Medicine and Center of Integrated Oncology at the University Hospital Cologne in Germany, and Head of the German CLL Study Group. "The approval of the Venclexta combination means that patients with previously untreated CLL now have a finite duration, chemotherapy-free treatment option that can allow them to live longer without disease progression, induce high rates of minimal residual disease (MRD) negativity and, importantly, allow them to complete their course of therapy within 12 months. This is a major step forward in how previously untreated CLL is managed and further supports the growing benefits offered by Venclexta in CLL."

The CLL14 trial demonstrated superior progression-free survival as assessed by an independent review committee (PFS; the time from initiation of treatment until disease progression or death) in patients treated with Venclexta plus obinutuzumab compared to patients who received chlorambucil plus obinutuzumab, a commonly used standard of care. With a median follow-up of 28 months (range: 0.1 to 36 months), Venclexta plus obinutuzumab reduced the risk of progression or death by 67% compared with chlorambucil plus obinutuzumab (hazard ratio: 0.33, 95% confidence interval [CI]: 0.22, 0.51; p<0.0001).1 Median PFS was not reached in either treatment arm.1  Minimal residual disease (MRD) negativity (undetectable disease in the blood or bone marrow) was assessed as a secondary endpoint and occurs when less than one CLL cell per 10,000 leukocytes can be detected using sensitive analytical methods.  Higher rates of MRD negativity were observed with Venclexta plus obinutuzumab compared to obinutuzumab plus chlorambucil in both bone marrow (57% versus 17%, p<0.0001) and peripheral blood (76% versus 35%, p<0.0001) three months after treatment completion .1

In the CLL14 trial, adverse events (AEs) were consistent with the known safety profiles of Venclexta and obinutuzumab alone. Serious adverse reactions (ARs) were reported in 49% of patients in the Venclexta plus obinutuzumab arm, most often due to febrile neutropenia and pneumonia (5% each). The most common ARs (≥15%) of any grade were neutropenia (60%), diarrhea (28%), fatigue (21%), nausea (19%), anemia (17%), and upper respiratory tract infection (17%).1 

Venclexta, an oral B-cell lymphoma-2 (BCL-2) inhibitor, has been granted five Breakthrough Therapy designations from the FDA.2,3,4,5,6

Venetoclax is being developed by AbbVie and Roche and 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 Chronic Lymphocytic Leukemia
CLL is typically a slow-progressing cancer of the bone marrow and blood in which types of white blood cells called B lymphocytes become cancerous and multiply abnormally.7 In the U.S., CLL accounts for more than 20,000 newly diagnosed cases of leukemia each year.7

About the CLL14 Trial                                                                                                        The prospective, multicenter, open-label, randomized Phase 3 CLL14 trial, which was conducted in close collaboration with the German CLL Study Group (DCLLSG), evaluated the efficacy and safety of a combined regimen of Venclexta and obinutuzumab (n=216) versus obinutuzumab and chlorambucil (n=216) in previously untreated patients with CLL and coexisting medical conditions (total Cumulative Illness Rating Scale [CIRS] score >6 or creatinine clearance <70 mL/min). The therapies were administered for a fixed duration of 12 months for Venclexta in combination with six cycles of obinutuzumab. The trial enrolled 432 patients, all of whom were previously untreated according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria. Efficacy was based on progression-free survival (PFS) as assessed by an Independent Review Committee (IRC).1,8

Key secondary endpoints were MRD negativity in peripheral blood and bone marrow, overall and complete response rates, MRD negativity in complete response in peripheral blood and bone marrow, and overall survival.8 

About Venclexta (venetoclax tablets) (US)                                                                    Venclexta 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. Venclexta targets the BCL-2 protein and works to help restore the process of apoptosis.1

Venclexta 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 being studied in several other hematologic malignancies including acute myeloid leukemia (AML), multiple myeloma (MM), non-Hodgkin lymphoma (NHL) and myelodysplastic syndrome (MDS).9,10,11,12,13

In April 2016, the U.S. FDA first granted accelerated approval of Venclexta for the treatment of patients with CLL with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy.14 The FDA approved this indication under accelerated approval based on overall response rate.14 Based on the results of the MURANO study, Venclexta was approved in June 2018 for the treatment of patients with CLL or SLL, with or without 17p deletion, who have received at least one prior therapy.1 In November 2018, Venclexta was approved 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.15

Venetoclax is approved in more than 50 countries, including the U.S. AbbVie, in collaboration with Roche, is currently working with regulatory agencies around the world to bring this medicine to additional eligible patients in need.

About AbbVie in Oncology                                                                                              At AbbVie, we strive to discover and develop medicines that deliver transformational improvements in cancer treatment by uniquely combining our deep knowledge in core areas of biology with cutting-edge technologies, and by working together with our partners – scientists, clinical experts, industry peers, advocates, and patients. We remain focused on delivering these transformative advances in treatment across some of the most debilitating and widespread cancers. We are also committed to exploring solutions to help patients obtain access to our cancer medicines. With the acquisitions of Pharmacyclics in 2015 and Stemcentrx in 2016, our research and development efforts, and through collaborations, AbbVie's oncology portfolio now consists of marketed medicines and a pipeline containing multiple new molecules being evaluated worldwide in more than 200 clinical trials and more than 20 different tumor types.

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