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12-month Phase 2a open-label extension clinical data in sickle cell disease shows patients on tovinontrine maintained reduced annualized rate of vaso-occlusive crises
BOSTON, Dec. 13, 2021 (GLOBE NEWSWIRE) -- Imara Inc. (Nasdaq: IMRA), a clinical-stage biopharmaceutical company dedicated to developing and commercializing novel therapeutics to treat subjects suffering from rare inherited genetic disorders of hemoglobin and other serious diseases, today announced the presentation of 12-month data from its Phase 2a open-label extension (OLE) trial for tovinontrine (IMR-687) as a potential treatment for sickle cell disease (SCD) at the American Society of Hematology (ASH) Annual Meeting, held December 11-14, 2021.
“These 12-month OLE data highlight the potential for tovinontrine to have longer term impact on VOC reductions. They also build upon previously-reported positive VOC results from the Phase 2a and OLE clinical trials,” said Rahul Ballal, Ph.D., President and Chief Executive Officer of Imara. “Reducing VOC rate is an established endpoint for regulatory approval and is becoming the primary endpoint of our ongoing Ardent Phase 2b clinical trial of tovinontrine in patients with sickle cell disease. We expect to report initial VOC data from the Ardent clinical trial in the first quarter of 2022 and continue to work with the FDA on a path towards registration.”
SCD OLE Data Highlights:
Imara is conducting a four-year OLE clinical trial, a safety and tolerability study comprised of patients who completed Imara’s Phase 2a clinical trial of tovinontrine in SCD. Subjects in the OLE clinical trial have received a once-daily dose of tovinontrine of 200 mg, and are in the process of being dose escalated to a once-daily dose of up to 400 mg. Of the 26 subjects enrolled, 21 were evaluable at month 12 as of the data cut-off.
Tovinontrine was generally well-tolerated as a monotherapy as well as in combination with hydroxyurea. There were no clinically-significant changes in lab safety data, ECGs or vital signs, and no patients have discontinued the study due to adverse events. The median annualized VOC rate was reduced by 38% in subjects previously in the placebo group in the Phase 2a clinical trial (N=7), with median annualized VOC rates of 5.0 (Phase 2a) and 3.1 (OLE) per year; median duration of treatment was 6.4 months and 11.6 months, respectively.
The low median annualized VOC rate for tovinontrine-treated patients in the Phase 2a clinical trial was maintained in subjects in the OLE clinical trial (N=14), with median annualized VOC rates of 0 (Phase 2a) and 2.0 (OLE) per year; median duration of treatment was 6.4 months and 11.8 months, respectively.
22% (4/18) of evaluable subjects had an absolute increase in fetal hemoglobin (HbF) greater than 3%. 47% (9/19) of subjects had an absolute increase in F-cells greater than 6%; F-cell increases were observed in 18 out of 19 evaluable subjects.
“We’re happy to be closing out 2021 by sharing positive 12-month VOC data for tovinontrine as a potential candidate to treat sickle cell disease,” said Dr. Ballal. “The Imara team is looking forward to making further progress in 2022 towards our goal of delivering accessible, effective treatment options for patients suffering from disorders of hemoglobin.”
Beta-thalassemia Preclinical Data Highlights:
In addition to the 12-month OLE data, Imara also reported preclinical data studying the effects of tovinontrine in beta-thalassemia mouse models. The preclinical results showed tovinontrine improved markers of beta-thalassemia, including an increase in total hemoglobin and red blood cell count. Based in part on these results, Imara is currently conducting the Forte Phase 2b clinical trial of tovinontrine in beta-thalassemia and expects to report data from transfusion-dependent subjects with beta-thalassemia in the first quarter of 2022.
Presentations at the American Society of Hematology (ASH) Annual Meeting:
Title: Treatment with IMR-687, a Highly Selective PDE9 Inhibitor, Increases HbF and Reduces VOCs in Adults with Sickle Cell Disease in a Long-Term, Phase 2a, Open-Label Extension Study
Presenter: Biree Andemariam, M.D., Associate Professor at UConn School of Medicine, Director of the New England Sickle Cell Institute at UConn Health
Title: PDE9 Inhibition By IMR-687 Improves Markers of Beta-Thalassemia in the Hbbth1/th1 Experimental Mouse Model
Presenter: Jennifer O’Cain, Ph.D., Imara Inc.
The presentations will be available on the Investors section of the Imara website.
About Tovinontrine (IMR-687)
Tovinontrine is a highly selective and potent small molecule inhibitor of phosphodiesterase-9 (PDE9). Tovinontrine has a multimodal mechanism of action that acts primarily on red blood cells, or RBCs, and has the potential to act on white blood cells, or WBCs, adhesion mediators and other cell types. PDE9 selectively degrades cyclic guanosine monophosphate (cGMP), an active signaling molecule that plays a role in vascular biology and hemoglobin production on RBCs. Lower levels of cGMP are found in people with sickle cell disease (SCD) and beta-thalassemia. Blocking PDE9 acts to increase cGMP levels, which is associated with lower WBC activation and reduced adhesion across various cell types, both of which also contribute to SCD, including the occurrence of vaso-occlusive crises (VOCs). Increasing cGMP levels is also associated with several additional benefits including the potential reactivation of fetal hemoglobin (HbF), a natural hemoglobin produced during fetal development. Increased levels of HbF in RBCs have been demonstrated to improve symptomology and substantially lower disease burden in both patients with SCD and patients with beta-thalassemia.
Imara Inc. is a clinical-stage biotechnology company dedicated to developing and commercializing novel therapeutics to treat patients suffering from rare inherited genetic disorders of hemoglobin and other serious diseases. Imara is advancing tovinontrine (IMR-687), a highly selective, potent small molecule inhibitor of PDE9 that is an oral, potentially disease-modifying treatment currently in clinical development for sickle cell disease and beta-thalassemia and preclinical development for heart failure with preserved ejection fraction, or HFpEF. Imara is also advancing IMR-261, an oral activator of nuclear factor erythroid 2–related factor 2, or Nrf2. For more information, please visit www.imaratx.com.
Cautionary Note Regarding Forward-Looking Statements
Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute “forward-looking statements” within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to (i) the timing for reporting of additional data from the Company’s Ardent and Forte Phase 2b clinical trials of tovinontrine (IMR-687) in patients with sickle cell disease and beta-thalassemia and (ii) the Company’s engagement with the FDA regarding tovinontrine and (iii) the Company’s beliefs regarding the strength of its clinical data, the therapeutic potential of tovinontrine and advancement of its development programs. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the impact of extraordinary external events, such as the risks and uncertainties resulting from the impact of the COVID-19 pandemic on the Company’s business, operations, strategy, goals and anticipated milestones, including its ongoing and planned research activities and ability to readout data from the Ardent and Forte Phase 2b clinical trials of tovinontrine in sickle cell disease and beta-thalassemia; the Company’s ability to advance the development of tovinontrine under the timelines it projects in current and future clinical trials, demonstrate in any current and future clinical trials the requisite safety and efficacy of tovinontrine; and other factors discussed in the “Risk Factors” section of the Company’s most recent Quarterly Report on Form 10-Q, which is on file with the Securities and Exchange Commission and in other filings that the Company makes with the Securities and Exchange Commission in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and the Company expressly disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.
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