• Data support early intervention in myelofibrosis to achieve better clinical outcomes in reduction in spleen volume (SVR), symptom score, bone marrow fibrosis (BMF), and anemia
  • Results are from an exploratory analysis of navitoclax plus ruxolitinib from Cohort 3 of the Phase 2 REFINE study in JAK inhibitor naïve myelofibrosis patients

NORTH CHICAGO, Illinois., June 10, 2022 /PRNewswire/ — AbbVie (NYSE: ABBV) today announced new data from Cohort 3 of its Phase 2 investigational REFINE study of navitoclax in combination with ruxolitinib in JAK inhibitor naïve patients with myelofibrosis (MF), a rare and difficult to treat blood cancer. These preliminary results show spleen volume and symptomatic improvement in this cohort. These data are consistent with data previously observed in relapsed/refractory patients in Cohort 1a1 and will be shared in an oral presentation at the 2022 European Hematology Association (EHA) Annual Congress (Abstract #S197).2

REFINE is a non-randomized, open-label, multicohort, phase 2 study evaluating the safety and efficacy of navitoclax alone or in combination with ruxolitinib in MF.

“Current treatment options for myelofibrosis are limited and focused on controlling the symptoms of the disease,” said mohamed zaki, MD, Ph.D., Vice President and Global Head of Oncology Clinical Development, AbbVie. “Along with the preclinical findings, early results from this study demonstrating the anti-fibrotic activity of navitoclax in combination with ruxolitinib are promising. Specifically, the data results regarding reduction in spleen volume, symptoms, and fibrosis of the bone marrow help support further exploration of the disease modifying myelofibrosis.”

The results presented at EHA 2022 were from a preliminary analysis of 32 patients with JAK inhibitor naïve MF from Cohort 3 of the Phase 2 REFINE trial (NCT03222609).2 The primary endpoint was reduction in spleen volume of ≥35% (SVR35) from baseline at week 24.2 Key secondary endpoints include ≥50% reduction in Total Symptom Score (TSS50) at week 24, anemia response, and reduction in BMF.2

In the results, SVR35 was achieved by 63% of evaluable patients at week 24 (20/32) and by 78% at any time during treatment (25/32).2 At week 24, 41% (11/27) of evaluable patients with measurable baseline symptoms achieved TSS50; notably, 67% of patients (18/27) achieved this endpoint at any time during the study.2 In this cohort, 35 percent of evaluable patients, with an available fibrosis grade at baseline and during the study, (9/26) achieved a BMF reduction of ≥ 1 grade at any time during the study with three patients with ≥2 grade reductions in BMF.2 Additionally, 40% of patients evaluable for anemic response (6/15) experienced improvement in anemia, a common clinical feature of MF.2

The preliminary security analysis did not identify any new security signals. Thirty-one (97%) patients reported one or more adverse events (AEs).1 The most common grade ≥3 AEs were thrombocytopenia (47%), anemia (34%) and neutropenia (25%).1 Seven patients (22%) reported having suffered serious AEs.1 Three patients (9%) experienced an AE leading to discontinuation of navitoclax and three patients (9%) reported an AE leading to discontinuation of ruxolitinib.2

“These data reinforce the importance of early intervention in myelofibrosis and the potential for improving clinical outcomes,” said Francesco Passamonti, Full Professor of Hematology at the University of Insubria and Head of Hematology Department at Varee Hospital. “These preliminary results show good responses to combination therapy with navitoclax that may continue to improve over time.”

About Navitoclax
Navitoclax is an investigational oral BCL-XL/BCL-2 inhibitor. The BCL-2 family of proteins are known regulators of the apoptosis pathway.3

Navitoclax is not currently approved by the United States Food and Drug Administration (FDA) or any health authority worldwide. Its safety and efficacy are being evaluated in Phase 2 studies and ongoing Phase 3 registration.

AbbVie has an extensive late-stage clinical trial program for investigational navitoclax that is currently being recruited. For more information about enrolling in a clinical trial, please visit us here.

About the REFINE study
REFINE is a multicenter, randomized, open-label, multicenter phase 2 study evaluating the safety and efficacy of navitoclax alone or when added to ruxolitinib in patients with myelofibrosis (MF).4 The primary outcome is the percentage of patients who achieve a reduction in spleen volume greater than or equal to 35% (SVR35) from baseline to week 24. Secondary outcomes include the percentage of participants achieving a reduction in 50% of total symptom score between baseline and week. 24 and change in grade of bone marrow fibrosis assessed according to the European Consensus Grading System.

Data presented at EHA 2022 include preliminary safety and efficacy results from REFINE Cohort 3 (n=32). Cohort 3 patients had primary or secondary MF with splenomegaly and had not received JAK-2 therapy or BET inhibitors prior to enrollment. Data presented at EHA 2022 are representative of data from Cohort 3 of the REFINE study at February 7, 2022.

Data included in the official EHA 2022 abstract book are representative of data from Cohort 3 of the REFINE study at October 42021.

More information can be found at https://www.clinicaltrials.gov/ (NCT03222609).

About myelofibrosis
Myelofibrosis (MF) is a rare and difficult to treat blood cancer that causes excessive scar tissue (fibrosis) to form in the bone marrow. Patients with MF present with symptoms such as an enlarged spleen, fatigue, weakness and severe anemia, which are often debilitating and have a significant impact on quality of life. MF also carries a risk of transformation into a more aggressive disease such as acute myeloid leukemia.4

About AbbVie in Oncology
At AbbVie, we are committed to transforming the standards of care for multiple blood cancers while advancing a dynamic pipeline of investigational therapies for a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potentially game-changing medicines. We’re evaluating more than 20 investigational drugs in more than 300 clinical trials for some of the world’s most common and debilitating cancers. As we strive to have a remarkable impact on people’s lives, we are committed to exploring solutions to help patients gain access to our cancer medicines. For more information, please visit http://www.abbvie.com/oncology.

About AbbVie
AbbVie’s mission is to discover and deliver innovative medicines that solve the serious health problems of today and meet the medical challenges of tomorrow. We strive to have a remarkable impact on people’s lives in several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women’s health and gastroenterology, in addition products and services from its Allergan Aesthetics portfolio. For more information about AbbVie, visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, instagram, Youtube and LinkedIn.

Forward-looking statements
Certain statements contained in this press release are, or may be deemed to be, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words “believe”, “expect”, “anticipate”, “project and similar expressions, among other things, 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. These risks and uncertainties include, but are not limited to, the failure to realize the anticipated benefits of the acquisition of Allergan plc by AbbVie (“Allergan”), the failure to quickly and effectively integrate the businesses of Allergan, competition from other products, intellectual property challenges, difficulties inherent in the research and development process, adverse litigation or government action, changes in laws and regulations applicable to our industry and the impact public health epidemics, epidemics or pandemics, such as COVID-19. Additional information about economic, competitive, governmental, technological and other factors that could affect AbbVie’s operations is set forth in Section 1A, “Risk Factors,” of 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 publicly release any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

References:

  1. Ruxolitinib with Navitoclax is effective and safe in myelofibrosis. Discovery of cancer May 1, 2022; 12 (5): OF4. https://doi.org/10.1158/2159-8290.CD-RW2022-037.
  2. Navitoclax plus ruxolitinib in JAK inhibitor naïve patients with myelofibrosis: preliminary safety and efficacy in a multicenter, open-label phase 2 study. [Oral Presentation S197]. Presented at the 2022 Congress of the European Hematology Association (EHA 2022), June 9-12, 2022.
  3. Harrison C, Garcia J, Somervaille T, et al. Addition of Navitoclax to ongoing ruxolitinib therapy for patients with myelofibrosis with progression or suboptimal response: Phase II Safety and Efficacy. J Clin Oncol. 2022; JCO2102188.
  4. Online Tsujimoto Y. (1998). Role of Bcl-2 family proteins in apoptosis: apoptosomes or mitochondria?. Genes to cells: devoted to molecular and cellular mechanisms, 3(11), 697-707. https://doi.org/10.1046/j.1365-2443.1998.00223.x

SOURCEAbbVie