- Exploratory analysis from Cohort 3 of the Phase 2 REFINE study presented in an oral session at ASH
NORTH CHICAGO, Ill. , Dec. 10, 2022 /PRNewswire/ — AbbVie (NYSE: ABBV ) today announced new data through Cohort 3 of its Stage 2 IMPROVE study associated with investigational navitoclax in combination with ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis (MF). The exploratory analysis suggests the particular combination of navitoclax and ruxolitinib led to reductions in bone marrow fibrosis (BMF) and variant allele frequency (VAF) for common genetic mutations found in individuals with myelofibrosis that may indicate potential disease modification. 1 The findings were shared in a dental presentation (abstract #237) in the 64 th American Society of Hematology Annual Meeting & Exposition (ASH).
“While the current standard of care with regard to patients with myelofibrosis can improve disease symptoms, impact on underlying disease biology is limited. It is our hope that patients have an option that goes beyond symptom control, ” said Mohamed Zaki , M. D., Ph. D., vice president plus global head of oncology clinical development, AbbVie. “Consistent with previous evidence, these results suggest navitoclax combination may possess disease modifying potential, both as an anti-fibrosis agent and by reducing variant allele frequency associated with driver variations. ”
REFINE (NCT03222609) is a Phase 2 non-randomized open-label multi-cohort study evaluating the safety plus efficacy of navitoclax alone or in conjunction with ruxolitinib in MF. 2
These data build on AbbVie’s history of transforming standards associated with care inside blood cancers, including recent presentations of investigational navitoclax data from the REFINE research earlier this year at the American Association for Cancer Research (AACR) Annual Conference and the particular European Hematology Association (EHA) Annual Congress .
The findings presented from ASH were based on an exploratory evaluation of 32 JAK inhibitor -naïve individuals with MF from Cohort 3 from the Phase two REFINE study. The primary endpoint was spleen volume reduction associated with ≥35 percent (SVR35) from baseline with week 24. one Key secondary and exploratory endpoints evaluated in this analysis were a reduction in BMF and a reduction in VAF for the driver gene mutations ( JAK2 V617 , CALR , MPL or Triple-negative), respectively. 1
In this exploratory analysis, SVR35 at week 24 has been observed in higher-risk groups, improving over time. The particular four poor prognosis subgroups were: Type (primary or secondary) of MF (primary MF, 59 % [n = 10/17]; age (≥75 years, 50 percent [n = 4/8]); prognostic risk score, as measured by Dynamic International Prognostic Scoring System or DIPSS (intermediate-2, 63 percent [n = 12/19]; high, 33 percent [n = 1/3]); and presence of high molecular danger (HMR) variations (47 % [n = 9/19]. one
In Cohort a few, BMF grade improvement had been evaluable within 81 percent (26/32) of patients. 1 Of these research participants, 35 percent (9/26) achieved ≥ 1 grade improvement at any time during treatment with a median time-to-improvement of 12. 3 weeks. one Complete resolution of BMF was seen in 22 % (2/9) associated with patients. 1
Reduction inside driver gene mutation VAF > 20% from baseline at 7 days 12 or even 24 was noticed in fifty percent (14/28) of sufferers, while 18 percent (5/28) of patients achieved > 50% VAF reduction through baseline. There were no differences in > twenty percent VAF cutbacks from primary to week 12 or 24 between those along with or without HMR mutations (47 percent [7/15] versus 54 percent [7/13], respectively).
Preliminary safety analysis identified no fresh safety signals. Twenty-five (78 percent) individuals reported one or more adverse events (AE). The most common grade ≥3 AEs had been thrombocytopenia (47 percent), anemia (34 percent), and neutropenia (25 percent). 9. 4 % of patients discontinued therapy due to an AE. a few
“These results are promising for sufferers who need a treatment choice that goes beyond just symptom control, ” stated Francesco Passamonti, full professor of hematology, University of Insubria and chief, hematology, Varese Hospital, Italy . “The suggestion associated with disease customization with this analysis from mixture therapy with navitoclax is encouraging, particularly when combined with clinical efficacy in terms of SVR35 rates in the higher risk groups that will improved over time. ”
Navitoclax is an investigational, oral BCL-XL/BCL-2 inhibitor. Navitoclax is not approved simply by any health authority worldwide at this time. Its safety plus efficacy are under evaluation as part of ongoing Phase 2 and registrational Phase three or more studies.
AbbVie has an extensive late-stage clinical trial program for investigational navitoclax that is currently enrolling. Please visit us here for a lot more information about enrolling in a clinical trial.
About the IMPROVE Study
REFINE will be a multi-cohort, Phase two, randomized, open-label, multicenter study evaluating the tolerability and efficacy of navitoclax by yourself or when added to ruxolitinib inside patients along with myelofibrosis (MF). 2 The primary outcome measure is the percentage of patients who achieve spleen quantity reduction of greater than or equal to 35 percent (SVR35) from baseline in order to week twenty-four. two Secondary outcomes measures include percentage associated with participants achieving 50 % reduction in total symptom score from base to 7 days 24; anemia response every 12 several weeks up to approximately 96 days, measured according to current International Working Group-Myeloproliferative Neoplasms Research plus European LeukemiaNet (IWG-MRT/ELN) criteria; and change in quality of bone tissue marrow fibrosis assessed in accordance to the particular European Consensus Grading System. 2
Information presented on ASH 2022 include security and effectiveness results from Cohort 3 of REFINE (n=32). Patients in Cohort 3 or more had main or extra MF with splenomegaly (DIPSS ≥ intermediate-1) and had not received JAK-2 therapy or even bromodomain and extra terminal motif (BET) inhibitors prior to enrollment. The main endpoint associated with SVR35 has been assessed by MRI conducted by central review. Key secondary plus exploratory endpoints evaluated within this analysis were a reduction in BMF obtained through BM biopsies by local evaluation and a decrease in VAF for that car owner gene variations (JAK2V617, CALR, or MPL), respectively. Studied HMR mutations included ASXL1, EZH2, SRSF2, IDH1/2, plus U2AF1 p. Q157. Driver gene VAF and HMR mutations had been determined in whole blood with the 50-gene focus myeloid next-generation sequencing panel. The results presented at ASH 2022 are representative of information from Cohort 3 of the REFINE research as of February 7, 2022 .
More information about the REFINE study can be found in https://www.clinicaltrials.gov/ (NCT03222609).
Myelofibrosis (MF) is really a rare, difficult-to-treat blood cancer that results in excessive scar tissue formation (fibrosis) in the bone marrow. Patients living with MF experience symptoms such while an enlarged spleen, fatigue, weakness, and severe anemia which are often debilitating and greatly impact quality of life. MF also carries a risk of transformation to more aggressive illness such as acute myeloid leukemia. 4
About AbbVie in Oncology
At AbbVie, we are committed to changing standards associated with care regarding multiple blood cancers while advancing a dynamic pipeline of investigational therapies across a range of malignancy types. Our dedicated plus experienced team joins forces with innovative partners to accelerate the particular delivery of potentially breakthrough medicines. We are evaluating more than 20 investigational medicines inside over 300 clinical trials across some of the world’s most widespread and debilitating malignancies. As we work to have a remarkable impact on people’s lives, we are committed to exploring solutions to help individuals obtain access to our own cancer medicines. For a lot more information, please visit https://www.abbvie.com/oncology and the Blood Malignancy Press Kit page .
AbbVie’s mission is to discover plus deliver revolutionary medicines that solve serious health issues today and address the particular medical challenges of tomorrow. We strive to have a remarkable effect on people’s lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women’s health plus gastroenterology, in addition in order to products and services throughout our Allergan Aesthetics portfolio. For more information about AbbVie, much more us at www.abbvie.com . Follow @abbvie upon Twitter , Facebook , Instagram , YouTube and LinkedIn .
Some statements in this particular news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act associated with 1995. The words “believe, inch “expect, inches “anticipate, ” “project” and similar expressions, among others, generally identify forward-looking claims. AbbVie cautions that these forward-looking statements are usually subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the particular forward-looking statements. Such dangers and questions include, but are not small to, failure to realize the expected benefits from AbbVie’s acquisition of Allergan plc (“Allergan”), failure to promptly plus effectively integrate Allergan’s businesses, competition through other products, challenges in order 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 particular impact of public wellness outbreaks, epidemics or pandemics, like COVID-19. Additional information regarding the economic, competitive, governmental, technological and other factors that could affect AbbVie’s operations is set forth inside Item 1A, “Risk Factors, ” associated with AbbVie’s 2021 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 kind of revisions in order to forward-looking claims as a result of subsequent events or even developments, except as required by law.
- Passamonti F, Foran J, Tandra A, et al. The particular Combination of Navitoclax and Ruxolitinib in GRUNZOCHSE Inhibitor-Naïve Individuals With Myelofibrosis Mediates Responses Suggestive of Disease Modification. [Oral Presentation #237]. Presented from 2022 American Society associated with Hematology (ASH) Annual Meeting and Exhibition, December 10-13, 2022 .
- ClinicalTrials. gov. The Study Evaluating Tolerability plus Efficacy of Navitoclax Alone or in Combination With Ruxolitinib in Participants Along with Myelofibrosis (REFINE). NCT03222609. Available at https://www.clinicaltrials.gov/ct2/show/NCT03222609 . Last accessed October 2022 .
- Navitoclax plus ruxolitinib in JAK inhibitor-naïve sufferers with myelofibrosis: Preliminary protection and efficiency in the multicenter, open-label Phase two study. [Oral Presentation S197]. Presented at European Hematology Organization 2022 Our elected representatives (EHA 2022), June 9-12, 2022 .
- Tsujimoto Y. (1998). Role of Bcl-2 family proteins in apoptosis: apoptosomes or mitochondria?. Genes to cells: devoted to molecular & cellular mechanisms, 3(11), 697–707. https://doi.org/10.1046/j.1365-2443.1998.00223.x