– Phase 3 MURANO results presented for the first time today as one of six late breaking abstracts during the 59th American Society of Hematology (ASH) Annual Meeting and Exposition in Atlanta, GA
– Prolonged progression-free survival (PFS) estimated at 24 months of 84.9 percent with VENCLEXTA/VENCLYXTO and Rituxan compared to 36.3 percent with bendamustine and Rituxan[1]
– An independent data monitoring committee reviewed the MURANO study, recommending the trial be unblinded based on the positive PFS results in the VENCLEXTA/VENCLYXTO and Rituxan arm
– At the time of the interim analysis, safety data were consistent with the known safety profiles of the medicines[1]
– Regulatory submissions to health authorities are underway based on MURANO results for this chemotherapy-free combination
NORTH CHICAGO, IL, USA I December 12, 2017 I AbbVie (NYSE: ABBV), a research and development based global biopharmaceutical company, today announced the first presentation of efficacy and safety results from MURANO, an international, multicenter, open-label, randomized Phase 3 study of VENCLEXTA™/VENCLYXTO™ (venetoclax) in combination with Rituxan® (rituximab) compared with bendamustine in combination with Rituxan in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL).
Investigator-assessed results showed that patients with R/R CLL achieved significantly prolonged median progression-free survival (PFS) with VENCLEXTA/VENCLYXTO in combination with Rituxan [median PFS, not reached], compared with bendamustine in combination with Rituxan [median PFS, 17.0 months; hazard ratio, 0.17; 95% CI, 0.11–0.25; P<0.0001].1 Twenty-four month PFS estimates were 84.9 percent and 36.3 percent, respectively.1 Independent Review Committee (IRC)-assessed PFS showed similar results.1 Additionally, consistent improvement in PFS was observed across the patient subgroups assessed in the trial, including patients with 17p deletion [hazard ratio 0.14; 95% CI, 0.06–0.33].1 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.
At the time of the interim analysis, safety data were consistent with the known safety profiles of the medicines.1
“The data from the MURANO trial represents the next evolution in a potential treatment option for patients with relapsed/refractory CLL, an indication for which we received Breakthrough Therapy Designation,” said Michael Severino, M.D., executive vice president, research and development, and chief scientific officer, AbbVie. “We are proud to present these findings at the ASH annual meeting and are working closely with regulatory authorities to bring this combination therapy to appropriate patients as soon as possible.”
The data also serves as the Phase 3 confirmatory study requested by the U.S. Food and Drug Administration (FDA) when VENCLEXTA was granted accelerated approval on April 11, 2016.2 Health authority regulatory submissions of VENCLEXTA/VENCLYXTO in combination with Rituxan are underway.
“This primary analysis of the MURANO trial showed a significant improvement in PFS with VENCLEXTA/VENCLYXTO and Rituxan versus bendamustine and Rituxan, with consistent results in all patient subsets assessed,” said John Seymour, M.D., Peter MacCallum Cancer Centre & Royal Melbourne Hospital in Australia and lead investigator of the MURANO trial. “Based on the efficacy and safety results of this trial, the VENCLEXTA/VENCLYXTO and Rituxan combination has the potential to offer a new chemotherapy-free regimen for patients with relapsed/refractory CLL. We continue to monitor safety and efficacy in trial patients to gain further data and information.”
Design and Results of Phase 3 Study Presented at ASH
A total of 389 patients with R/R CLL who had received one to three prior therapies were enrolled in the international, multicenter, open-label, randomized Phase 3 MURANO study.1 The study was designed to evaluate the efficacy and safety of VENCLEXTA/VENCLYXTO in combination with Rituxan (194 patients; median age, 64.5 years) compared with bendamustine in combination with Rituxan (195 patients; median age, 66.0 years).1
For patients receiving VENCLEXTA/VENCLYXTO in combination with Rituxan, a 4-week or 5-week dose ramp-up of VENCLEXTA/VENCLYXTO from 20 to 400 mg daily was used to mitigate potential tumor lysis syndrome (TLS) risk.1 Beginning at week 6, intravenous (IV) Rituxan was given monthly for six 28-day cycles (375 mg/m2 first dose, then 500 mg/m2).1 Patients continued with VENCLEXTA/VENCLYXTO 400 mg for a maximum of two years or until disease progression, whichever was first.1 For patients receiving bendamustine in combination with Rituxan, patients were given bendamustine (70 mg/m2 IV) on days 1 and 2 of each of six 28-day cycles in combination with Rituxan using the same dosing schedule.1
The primary endpoint was investigator-assessed PFS, which was determined using standard International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines.3 Secondary endpoints included Independent Review Committee (IRC)-assessed PFS, as well as PFS in patients with 17p deletion, best overall response (defined as complete response [CR], complete response with incomplete marrow recovery [CRi], nodular partial response [nPR], or partial response [PR]), overall survival (OS), event-free survival, duration of response, time to next anti-CLL treatment, and percentage of patients achieving minimal residual disease (MRD)-negativity.3 As of May 8, 2017, median follow-up was 23.8 months (range, 0-37.4 months).1
Study Results:1
|
Endpoint*
|
Investigator-Assessed |
Independent Review Committee |
| Progression-Free Survival |
VR: 84.9% |
VR: 82.8%4 |
| (24-month estimate) |
BR: 36.3% |
BR: 37.4%4 |
| |
|
|
| Median PFS |
VR: Not reached |
VR: Not reached4 |
| |
BR: 17.0 months |
BR: 18.1 months4 |
| |
|
|
| |
|
|
| HR (95% CI) |
HR=0.17 (0.11–0.25) |
HR=0.19 (0.13- 0.28) |
| P-value |
P <0.0001 |
P <0.0001 |
| |
|
|
| Overall Response |
VR: 93.3% (181/194) |
VR: 92.3% (179/194) |
| (CR, CRi, PR, nPR) |
BR: 67.7% (132/195) |
BR: 72.3% (141/195) |
| |
|
|
| Difference (95% CI) |
25.6% (17.9-33.3) |
20.0% (12.4-27.6) |
| |
|
|
| Complete Response |
VR: 26.8% (52/194) |
VR: 8.2% (16/194) |
| (CR/CRi) |
BR: 8.2% (16/195) |
BR: 3.6% (7/195) |
| |
|
|
| Difference (95% CI) |
18.6% |
4.7% (-0.3, 9.6) |
| P-value |
|
P=NS |
| |
|
|
| Partial Response |
VR: 66.5% (129/194) |
VR: 84.0% (163/194) |
| (PR/nPR) |
BR: 59.5% (116/195)
|
BR: 68.7% (134/195) |
| Overall Survival |
|
| (OS) |
|
| |
|
| Events |
VR 7.7% (15/194)4 |
| |
BR 13.8% (27/195)4 |
| |
|
| HR (95% CI) |
HR =0.48 (0.25-0.90)4 |
| |
|
| Peripheral blood Minimal Residual Disease Negativity |
VR: 83.5% (162/194)
BR: 23.1% (45/195) |
| (MRD-)** |
|
| |
|
| Difference (95% CI) |
60.4% (52.3–68.6) |
| *Abbreviations: VR (VENCLYXTO/VENCLEXTA+ Rituxan); BR (bendamustine + Rituxan); NS (not significant) |
| ** Best response at any timepoint; MRD negativity was defined as less than 1 CLL cell in 10,000 leukocytes |
In the study, the adverse events (AEs) were consistent with the known safety profile of VENCLEXTA/VENCLYXTO and Rituxan. Grade 3-4 neutropenia was higher in the VENCLEXTA/VENCLYXTO in combination with Rituxan arm of the trial. 1 For patients taking VENCLEXTA/VENCLYXTO in combination with Rituxan and bendamustine in combination with Rituxan, there were 6 (3.1 percent) and 2 (1.1 percent) grade ≥3 TLS AEs reported in each arm, respectively.1 For VENCLEXTA/VENCLYXTO in combination with Rituxan versus bendamustine in combination with Rituxan, respectively, Richter transformation was confirmed in 6 and 5 patients, and AEs leading to death were seen in 10 (5.2 percent) versus 11 (5.9 percent) patients.1
Summary of Adverse Events (AEs):1
|
Adverse Events*
|
Venetoclax in combination with
rituximab (N= 194)
|
Bendamustine in combination with
rituximab (N=195)
|
| Number of AEs |
335 |
255 |
|
Grade 3-4 AEs occurring in > 5
percent in either arm, n (%)
Neutropenia
Anemia
Thrombocytopenia
Febrile neutropenia
Pneumonia
Infusion-related reaction
|
112 (57.7)
21 (10.8)
11 (5.7)
7 (3.6)
10 (5.2)
3 (1.5)
|
73 (38.8)
26 (13.8)
19 (10.1)
18 (9.6)
15 (8.0)
10 (5.3)
|
|
Serious AEs in > 2 patients
in either arm, n (%)
Pneumonia
Influenza
Sepsis
Upper respiratory tract infection
Lung infection
Sinusitis
Appendicitis
Bronchitis
Pharyngitis
Respiratory tract infection
|
16 (8.2)
3 (1.5)
1 (0.5)
3 (1.5)
3 (1.5)
2 (1.0)
2 (1.0)
0
0
2 (1.0)
|
15 (8.0)
2 (1.1)
4 (2.1)
2 (1.1)
0
1 (0.5)
0
2 (1.1)
2 (1.1)
0
|
| Fatal AEs, n (%) |
10 (5.2) |
11 (5.9) |
| *AE reporting period: up to 90 days after end of bendamustine and rituximab treatment (maximum six months); up to 28 days after end of venetoclax and rituximab treatment (maximum two years). |
About VENCLEXTA™/VENCLYXTO™
VENCLEXTA/VENCLYXTO is an oral B-cell lymphoma-2 (BCL-2) inhibitor that targets a specific protein in the body called BCL-2.2,5 When you have CLL, BCL-2 may build up and prevent cancer cells from self-destructing naturally.2,5 VENCLEXTA/VENCLYXTO targets BCL-2 in order to help restore the process of apoptosis.2,5 Through apoptosis, your body allows cancer cells and normal cells to self-destruct.2,5
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 with venetoclax, which is currently being evaluated in clinical trials in several hematologic cancers.
VENCLEXTA/VENCLYXTO is currently approved in 49 nations, including the U.S., and in the EU. AbbVie, in collaboration with Roche and Genentech, is currently working with regulatory agencies around the world to bring this medicine to eligible patients in need.
About VENCLYXTO™ (venetoclax) Tablets (EU)
VENCLYXTO™ (venetoclax) is indicated in the European Union (EU) for the treatment of chronic lymphocytic leukemia (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; and for the treatment of CLL in the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.5 It is also being evaluated for the treatment of patients with various blood cancer types. 1,6,7,8,9 The BCL-2 protein prevents apoptosis (programmed cell death) of some cells, including lymphocytes, and can be overexpressed in CLL cells.1 VENCLYXTO, which is given once-daily, is designed to selectively inhibit the function of the BCL-2 protein.1
About VENCLEXTA™ (venetoclax) tablets (US)
In April 2016, the U.S. Food and Drug Administration (FDA) granted accelerated approval of VENCLEXTA™ (venetoclax) tablets 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.2 The FDA approved this indication under accelerated approval based on overall response rate, and continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial.
VENCLEXTA has been granted four Breakthrough Therapy Designations from the FDA including for the combination treatment of patients with untreated AML not eligible for standard induction chemotherapy. This designation is intended to expedite the development and review of therapies for serious or life-threatening conditions.10 In January 2016, AbbVie announced that the FDA granted priority review for the single agent NDA application for VENCLEXTA.
In November 2017, AbbVie and Genentech received the Prix Galien award for “Best Pharmaceutical Product” for VENCLEXTA.11
What is VENCLEXTA™ (venetoclax)?
VENCLEXTA™ (venetoclax) is a prescription medicine used to treat people with chronic lymphocytic leukemia (CLL) with 17p deletion who have received at least one prior treatment.
VENCLEXTA was approved based on response rate. There is an ongoing study to find out how VENCLEXTA works over a longer period of time.
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. For more information, please visit http://abbvieoncology.com.
About AbbVie
AbbVie is a global, research-driven biopharmaceutical company committed to developing innovative advanced therapies for some of the world’s most complex and critical conditions. The company’s mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook or LinkedIn.
1 American Society of Hematology 59th Annual Meeting and Exposition; December 9-12, 2017; Atlanta, GA. (2017). LBA-2 Venetoclax Plus Rituximab Is Superior to Bendamustine Plus Rituximab in Patients with Relapsed/ Refractory Chronic Lymphocytic Leukemia – Results from Pre-Planned Interim Analysis of the Randomized Phase 3 Murano Study. https://ash.confex.com/ash/2017/webprogram/Paper109076.html. Accessed November 2017.
2 Venclexta (venetoclax) [Package Insert]. North Chicago, Ill.: AbbVie Inc.
3 Clinicaltrials.gov. NCT02005471: A Study of Venetoclax in Combination With Rituximab Compared With Bendamustine in Combination With Rituximab in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia
4 American Society of Hematology 2017 Annual Meeting and Exposition. MURANO Study Interim Analysis Results. Presentation. December 12, 2017.
5 Venclyxto (venetoclax) Summary of Product Characteristics. December 2016.
6 Clinicaltrials.gov. NCT01994837: A Phase 2 Study of ABT-199 in subjects with Acute Myelogenous Leukemia (AML). Accessed October 2016.
7 Clinicaltrials.gov. NCT01794520: Study evaluating ABT-199 in subjects with relapsed or refractory Multiple Myeloma. Accessed October 2016.
8 Clinicaltrials.gov. NCT01328626: A Phase 1 study evaluating the safety and pharmacokinetics of ABT-199 in subjects with relapsed or refractory Chronic Lymphocytic Leukemia and Non-Hodgkin Lymphoma. Accessed October 2016
9 Clinicaltrials.gov. NCT01889186: A study of the efficacy of ABT-199 in subjects with relapsed or refractory chronic lymphocytic leukemia with the 17p deletion. Accessed October 2016
10 U.S. Food and Drug Administration. Fact Sheet: Breakthrough Therapies. Available from: https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/FDASIA/ucm329491.htm. Accessed November 2017
11 Galien Foundation. The Galien Foundation Honors Excellence in Scientific Innovation and Humanitarian Efforts at 2017 Prix Galien Awards Gala. Available from: https://www.prnewswire.com/news-releases/the-galien-foundation-honors-excellence-in-scientific-innovation-and-humanitarian-efforts-at-2017-prix-galien-awards-gala-300543930.html. Accessed November 2017.
SOURCE: AbbVie
Post Views: 34
– Phase 3 MURANO results presented for the first time today as one of six late breaking abstracts during the 59th American Society of Hematology (ASH) Annual Meeting and Exposition in Atlanta, GA
– Prolonged progression-free survival (PFS) estimated at 24 months of 84.9 percent with VENCLEXTA/VENCLYXTO and Rituxan compared to 36.3 percent with bendamustine and Rituxan[1]
– An independent data monitoring committee reviewed the MURANO study, recommending the trial be unblinded based on the positive PFS results in the VENCLEXTA/VENCLYXTO and Rituxan arm
– At the time of the interim analysis, safety data were consistent with the known safety profiles of the medicines[1]
– Regulatory submissions to health authorities are underway based on MURANO results for this chemotherapy-free combination
NORTH CHICAGO, IL, USA I December 12, 2017 I AbbVie (NYSE: ABBV), a research and development based global biopharmaceutical company, today announced the first presentation of efficacy and safety results from MURANO, an international, multicenter, open-label, randomized Phase 3 study of VENCLEXTA™/VENCLYXTO™ (venetoclax) in combination with Rituxan® (rituximab) compared with bendamustine in combination with Rituxan in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL).
Investigator-assessed results showed that patients with R/R CLL achieved significantly prolonged median progression-free survival (PFS) with VENCLEXTA/VENCLYXTO in combination with Rituxan [median PFS, not reached], compared with bendamustine in combination with Rituxan [median PFS, 17.0 months; hazard ratio, 0.17; 95% CI, 0.11–0.25; P<0.0001].1 Twenty-four month PFS estimates were 84.9 percent and 36.3 percent, respectively.1 Independent Review Committee (IRC)-assessed PFS showed similar results.1 Additionally, consistent improvement in PFS was observed across the patient subgroups assessed in the trial, including patients with 17p deletion [hazard ratio 0.14; 95% CI, 0.06–0.33].1 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.
At the time of the interim analysis, safety data were consistent with the known safety profiles of the medicines.1
“The data from the MURANO trial represents the next evolution in a potential treatment option for patients with relapsed/refractory CLL, an indication for which we received Breakthrough Therapy Designation,” said Michael Severino, M.D., executive vice president, research and development, and chief scientific officer, AbbVie. “We are proud to present these findings at the ASH annual meeting and are working closely with regulatory authorities to bring this combination therapy to appropriate patients as soon as possible.”
The data also serves as the Phase 3 confirmatory study requested by the U.S. Food and Drug Administration (FDA) when VENCLEXTA was granted accelerated approval on April 11, 2016.2 Health authority regulatory submissions of VENCLEXTA/VENCLYXTO in combination with Rituxan are underway.
“This primary analysis of the MURANO trial showed a significant improvement in PFS with VENCLEXTA/VENCLYXTO and Rituxan versus bendamustine and Rituxan, with consistent results in all patient subsets assessed,” said John Seymour, M.D., Peter MacCallum Cancer Centre & Royal Melbourne Hospital in Australia and lead investigator of the MURANO trial. “Based on the efficacy and safety results of this trial, the VENCLEXTA/VENCLYXTO and Rituxan combination has the potential to offer a new chemotherapy-free regimen for patients with relapsed/refractory CLL. We continue to monitor safety and efficacy in trial patients to gain further data and information.”
Design and Results of Phase 3 Study Presented at ASH
A total of 389 patients with R/R CLL who had received one to three prior therapies were enrolled in the international, multicenter, open-label, randomized Phase 3 MURANO study.1 The study was designed to evaluate the efficacy and safety of VENCLEXTA/VENCLYXTO in combination with Rituxan (194 patients; median age, 64.5 years) compared with bendamustine in combination with Rituxan (195 patients; median age, 66.0 years).1
For patients receiving VENCLEXTA/VENCLYXTO in combination with Rituxan, a 4-week or 5-week dose ramp-up of VENCLEXTA/VENCLYXTO from 20 to 400 mg daily was used to mitigate potential tumor lysis syndrome (TLS) risk.1 Beginning at week 6, intravenous (IV) Rituxan was given monthly for six 28-day cycles (375 mg/m2 first dose, then 500 mg/m2).1 Patients continued with VENCLEXTA/VENCLYXTO 400 mg for a maximum of two years or until disease progression, whichever was first.1 For patients receiving bendamustine in combination with Rituxan, patients were given bendamustine (70 mg/m2 IV) on days 1 and 2 of each of six 28-day cycles in combination with Rituxan using the same dosing schedule.1
The primary endpoint was investigator-assessed PFS, which was determined using standard International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines.3 Secondary endpoints included Independent Review Committee (IRC)-assessed PFS, as well as PFS in patients with 17p deletion, best overall response (defined as complete response [CR], complete response with incomplete marrow recovery [CRi], nodular partial response [nPR], or partial response [PR]), overall survival (OS), event-free survival, duration of response, time to next anti-CLL treatment, and percentage of patients achieving minimal residual disease (MRD)-negativity.3 As of May 8, 2017, median follow-up was 23.8 months (range, 0-37.4 months).1
Study Results:1
|
Endpoint*
|
Investigator-Assessed |
Independent Review Committee |
| Progression-Free Survival |
VR: 84.9% |
VR: 82.8%4 |
| (24-month estimate) |
BR: 36.3% |
BR: 37.4%4 |
| |
|
|
| Median PFS |
VR: Not reached |
VR: Not reached4 |
| |
BR: 17.0 months |
BR: 18.1 months4 |
| |
|
|
| |
|
|
| HR (95% CI) |
HR=0.17 (0.11–0.25) |
HR=0.19 (0.13- 0.28) |
| P-value |
P <0.0001 |
P <0.0001 |
| |
|
|
| Overall Response |
VR: 93.3% (181/194) |
VR: 92.3% (179/194) |
| (CR, CRi, PR, nPR) |
BR: 67.7% (132/195) |
BR: 72.3% (141/195) |
| |
|
|
| Difference (95% CI) |
25.6% (17.9-33.3) |
20.0% (12.4-27.6) |
| |
|
|
| Complete Response |
VR: 26.8% (52/194) |
VR: 8.2% (16/194) |
| (CR/CRi) |
BR: 8.2% (16/195) |
BR: 3.6% (7/195) |
| |
|
|
| Difference (95% CI) |
18.6% |
4.7% (-0.3, 9.6) |
| P-value |
|
P=NS |
| |
|
|
| Partial Response |
VR: 66.5% (129/194) |
VR: 84.0% (163/194) |
| (PR/nPR) |
BR: 59.5% (116/195)
|
BR: 68.7% (134/195) |
| Overall Survival |
|
| (OS) |
|
| |
|
| Events |
VR 7.7% (15/194)4 |
| |
BR 13.8% (27/195)4 |
| |
|
| HR (95% CI) |
HR =0.48 (0.25-0.90)4 |
| |
|
| Peripheral blood Minimal Residual Disease Negativity |
VR: 83.5% (162/194)
BR: 23.1% (45/195) |
| (MRD-)** |
|
| |
|
| Difference (95% CI) |
60.4% (52.3–68.6) |
| *Abbreviations: VR (VENCLYXTO/VENCLEXTA+ Rituxan); BR (bendamustine + Rituxan); NS (not significant) |
| ** Best response at any timepoint; MRD negativity was defined as less than 1 CLL cell in 10,000 leukocytes |
In the study, the adverse events (AEs) were consistent with the known safety profile of VENCLEXTA/VENCLYXTO and Rituxan. Grade 3-4 neutropenia was higher in the VENCLEXTA/VENCLYXTO in combination with Rituxan arm of the trial. 1 For patients taking VENCLEXTA/VENCLYXTO in combination with Rituxan and bendamustine in combination with Rituxan, there were 6 (3.1 percent) and 2 (1.1 percent) grade ≥3 TLS AEs reported in each arm, respectively.1 For VENCLEXTA/VENCLYXTO in combination with Rituxan versus bendamustine in combination with Rituxan, respectively, Richter transformation was confirmed in 6 and 5 patients, and AEs leading to death were seen in 10 (5.2 percent) versus 11 (5.9 percent) patients.1
Summary of Adverse Events (AEs):1
|
Adverse Events*
|
Venetoclax in combination with
rituximab (N= 194)
|
Bendamustine in combination with
rituximab (N=195)
|
| Number of AEs |
335 |
255 |
|
Grade 3-4 AEs occurring in > 5
percent in either arm, n (%)
Neutropenia
Anemia
Thrombocytopenia
Febrile neutropenia
Pneumonia
Infusion-related reaction
|
112 (57.7)
21 (10.8)
11 (5.7)
7 (3.6)
10 (5.2)
3 (1.5)
|
73 (38.8)
26 (13.8)
19 (10.1)
18 (9.6)
15 (8.0)
10 (5.3)
|
|
Serious AEs in > 2 patients
in either arm, n (%)
Pneumonia
Influenza
Sepsis
Upper respiratory tract infection
Lung infection
Sinusitis
Appendicitis
Bronchitis
Pharyngitis
Respiratory tract infection
|
16 (8.2)
3 (1.5)
1 (0.5)
3 (1.5)
3 (1.5)
2 (1.0)
2 (1.0)
0
0
2 (1.0)
|
15 (8.0)
2 (1.1)
4 (2.1)
2 (1.1)
0
1 (0.5)
0
2 (1.1)
2 (1.1)
0
|
| Fatal AEs, n (%) |
10 (5.2) |
11 (5.9) |
| *AE reporting period: up to 90 days after end of bendamustine and rituximab treatment (maximum six months); up to 28 days after end of venetoclax and rituximab treatment (maximum two years). |
About VENCLEXTA™/VENCLYXTO™
VENCLEXTA/VENCLYXTO is an oral B-cell lymphoma-2 (BCL-2) inhibitor that targets a specific protein in the body called BCL-2.2,5 When you have CLL, BCL-2 may build up and prevent cancer cells from self-destructing naturally.2,5 VENCLEXTA/VENCLYXTO targets BCL-2 in order to help restore the process of apoptosis.2,5 Through apoptosis, your body allows cancer cells and normal cells to self-destruct.2,5
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 with venetoclax, which is currently being evaluated in clinical trials in several hematologic cancers.
VENCLEXTA/VENCLYXTO is currently approved in 49 nations, including the U.S., and in the EU. AbbVie, in collaboration with Roche and Genentech, is currently working with regulatory agencies around the world to bring this medicine to eligible patients in need.
About VENCLYXTO™ (venetoclax) Tablets (EU)
VENCLYXTO™ (venetoclax) is indicated in the European Union (EU) for the treatment of chronic lymphocytic leukemia (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; and for the treatment of CLL in the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.5 It is also being evaluated for the treatment of patients with various blood cancer types. 1,6,7,8,9 The BCL-2 protein prevents apoptosis (programmed cell death) of some cells, including lymphocytes, and can be overexpressed in CLL cells.1 VENCLYXTO, which is given once-daily, is designed to selectively inhibit the function of the BCL-2 protein.1
About VENCLEXTA™ (venetoclax) tablets (US)
In April 2016, the U.S. Food and Drug Administration (FDA) granted accelerated approval of VENCLEXTA™ (venetoclax) tablets 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.2 The FDA approved this indication under accelerated approval based on overall response rate, and continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial.
VENCLEXTA has been granted four Breakthrough Therapy Designations from the FDA including for the combination treatment of patients with untreated AML not eligible for standard induction chemotherapy. This designation is intended to expedite the development and review of therapies for serious or life-threatening conditions.10 In January 2016, AbbVie announced that the FDA granted priority review for the single agent NDA application for VENCLEXTA.
In November 2017, AbbVie and Genentech received the Prix Galien award for “Best Pharmaceutical Product” for VENCLEXTA.11
What is VENCLEXTA™ (venetoclax)?
VENCLEXTA™ (venetoclax) is a prescription medicine used to treat people with chronic lymphocytic leukemia (CLL) with 17p deletion who have received at least one prior treatment.
VENCLEXTA was approved based on response rate. There is an ongoing study to find out how VENCLEXTA works over a longer period of time.
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. For more information, please visit http://abbvieoncology.com.
About AbbVie
AbbVie is a global, research-driven biopharmaceutical company committed to developing innovative advanced therapies for some of the world’s most complex and critical conditions. The company’s mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook or LinkedIn.
1 American Society of Hematology 59th Annual Meeting and Exposition; December 9-12, 2017; Atlanta, GA. (2017). LBA-2 Venetoclax Plus Rituximab Is Superior to Bendamustine Plus Rituximab in Patients with Relapsed/ Refractory Chronic Lymphocytic Leukemia – Results from Pre-Planned Interim Analysis of the Randomized Phase 3 Murano Study. https://ash.confex.com/ash/2017/webprogram/Paper109076.html. Accessed November 2017.
2 Venclexta (venetoclax) [Package Insert]. North Chicago, Ill.: AbbVie Inc.
3 Clinicaltrials.gov. NCT02005471: A Study of Venetoclax in Combination With Rituximab Compared With Bendamustine in Combination With Rituximab in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia
4 American Society of Hematology 2017 Annual Meeting and Exposition. MURANO Study Interim Analysis Results. Presentation. December 12, 2017.
5 Venclyxto (venetoclax) Summary of Product Characteristics. December 2016.
6 Clinicaltrials.gov. NCT01994837: A Phase 2 Study of ABT-199 in subjects with Acute Myelogenous Leukemia (AML). Accessed October 2016.
7 Clinicaltrials.gov. NCT01794520: Study evaluating ABT-199 in subjects with relapsed or refractory Multiple Myeloma. Accessed October 2016.
8 Clinicaltrials.gov. NCT01328626: A Phase 1 study evaluating the safety and pharmacokinetics of ABT-199 in subjects with relapsed or refractory Chronic Lymphocytic Leukemia and Non-Hodgkin Lymphoma. Accessed October 2016
9 Clinicaltrials.gov. NCT01889186: A study of the efficacy of ABT-199 in subjects with relapsed or refractory chronic lymphocytic leukemia with the 17p deletion. Accessed October 2016
10 U.S. Food and Drug Administration. Fact Sheet: Breakthrough Therapies. Available from: https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/FDASIA/ucm329491.htm. Accessed November 2017
11 Galien Foundation. The Galien Foundation Honors Excellence in Scientific Innovation and Humanitarian Efforts at 2017 Prix Galien Awards Gala. Available from: https://www.prnewswire.com/news-releases/the-galien-foundation-honors-excellence-in-scientific-innovation-and-humanitarian-efforts-at-2017-prix-galien-awards-gala-300543930.html. Accessed November 2017.
SOURCE: AbbVie
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