Imara Inc. (Nasdaq: IMRA) today announced results from interim
analyses of its Ardent Phase 2b clinical trial of tovinontrine
(IMR-687) in patients with sickle cell disease (SCD) and Forte
Phase 2b clinical trial of tovinontrine in patients with
beta-thalassemia. Imara also announced that because of the data
generated by these interim analyses, the company will discontinue
the Ardent and Forte trials as well as the further development of
tovinontrine in sickle cell disease and beta-thalassemia.
“We are disappointed in the outcome of both of the interim
analyses in our Phase 2b studies for sickle cell disease and
beta-thalassemia, and particularly that the Ardent trial interim
analysis did not replicate our previously observed positive
vaso-occlusive crisis data,” said Rahul Ballal, Ph.D., President
and Chief Executive Officer of Imara. “We plan to discontinue both
studies during the second quarter. As we do this, we remain deeply
grateful to the patients, investigators and their teams for their
participation in these trials and to the extended Imara team for
their role and dedication in generating the comprehensive interim
results."
Dr. Ballal continued, "Moving forward, we plan to consider our
strategic options, including development of tovinontrine in heart
failure with preserved ejection fraction (HFpEF) as well IMR-261
clinical development plans.”
Ardent Phase 2b Sickle Cell Disease Interim
Analysis:The interim analysis for the Ardent trial was
conducted when all participants completed the week 24 assessment or
terminated early. The intent-to-treat (ITT) population was used for
the primary efficacy analysis, which is a comparison of the median
annualized vaso-occlusive crisis (VOC) rate between the high dose
tovinontrine group (n=47, once daily oral dose of 300 mg or 400 mg
based on patient weight) and placebo group (n=32).
Safety was analyzed across all participants enrolled in the
Ardent trial, including the high dose, low dose (n=33, 200 mg or
300 mg once daily oral dose based on patient weight) and placebo
groups. Data from the interim analysis demonstrated that
tovinontrine was generally well-tolerated, with the most frequent
adverse events (≥10% of participants in any treatment group)
considered at least possibly related to study drug by the
investigator being nausea, headache, dizziness and vomiting. Four
(3.6%) participants discontinued prior to week 24 due to adverse
events.
The median annualized VOC rate in the placebo group was 2.02
VOCs per year and was 1.89 VOCs per year in the high dose
tovinontrine group, for a treatment difference of 0.13 VOCs per
year, or 6.4%. Based on the minimal decrease observed in VOCs with
the high dose and low VOC rate in the placebo arm, Imara enacted an
addendum to the statistical analysis plan for the trial and noted
trends of VOC benefit with tovinontrine. The median annualized rate
of VOCs in the low dose tovinontrine group was zero, as compared to
2.02 in the placebo group, and as compared to placebo, the low dose
tovinontrine group experienced an increase in median time to first
VOC and a higher proportion of participants who were VOC-free. A
trend for lower median annualized rate of VOCs was also observed
for participants in the high and low dose tovinontrine groups on
monotherapy (not on background hydroxyurea) as compared to placebo.
Although these additional data are encouraging, none were
statistically significant. In addition, no meaningful difference
was observed in fetal hemoglobin (HbF) response in either the high
or low dose tovinontrine groups as compared to placebo.
Collectively, the overall additional data did not materially
increase the likelihood of success for this trial.
Forte Phase 2b Beta-thalassemia Interim
Analysis:The Forte trial interim analysis evaluated safety
and biomarker data for both transfusion-dependent thalassemia (TDT)
and non-transfusion-dependent thalassemia (NTDT) cohorts, as well
as data on transfusion burden reduction in the TDT cohort. In both
cohorts, tovinontrine was well-tolerated, with the most frequent
adverse events (≥10% of participants in any treatment group)
considered at least possibly related to study drug by the
investigator being nausea and headache. One NTDT and eight TDT
participants (3.3% and 10.8%, respectively) discontinued study drug
due to adverse events.
Participants in the TDT cohort of the Forte trial were
randomized to either placebo (n=20), low dose (n=25, 200 mg or 300
mg) or high dose (n=29, 300 mg or 400 mg). No meaningful benefit
was observed in transfusion burden in either tovinontrine group
when compared to placebo. Participants in the NTDT cohort of the
Forte trial were randomized to either placebo (n=7), low-dose group
(n=8, 200 mg or 300 mg), or high-dose group (n=14, 300 mg or 400
mg). No meaningful improvements were observed in most
disease-related biomarkers, including total hemoglobin (Hb).
About the Ardent Phase 2b Clinical TrialThe
Ardent study was a randomized, double-blind, placebo-controlled,
multicenter Phase 2b study in adult patients with sickle cell
disease (SCD) randomized to either placebo, low-dose tovinontrine
(200 mg or 300 mg) or high-dose tovinontrine (300 mg or 400 mg).
The primary efficacy endpoint was annualized rate of VOCs in
participants dosed with high dose tovinontrine as compared to
placebo. The key secondary endpoints were time to first VOC and
proportion of participants with fetal hemoglobin (HbF) response,
defined as an absolute increase from baseline of at least 3% in HbF
in the high dose group vs placebo.
About the Forte Phase 2b Clinical TrialThe
Forte study was a randomized, double-blind, placebo-controlled,
multicenter Phase 2b clinical trial evaluating the safety and
tolerability of tovinontrine in adult patients with
beta-thalassemia. Patient randomization was stratified by
transfusion-dependent thalassemia (TDT) or
non-transfusion-dependent thalassemia (NTDT). The primary objective
of the study was safety and tolerability. For TDT participants, the
clinical trial also evaluated the effect of tovinontrine versus
placebo in reducing transfusion burden. For NTDT participants, the
clinical trial also evaluated the effect of tovinontrine versus
placebo on fetal hemoglobin as well as total hemoglobin.
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 on red blood cells, white blood cells, adhesion
molecules and blood vessels. PDE9 selectively degrades cyclic
guanosine monophosphate (cGMP), an active signaling molecule that
plays a role in vascular biology.
About ImaraImara Inc. is a clinical-stage
biotechnology company dedicated to developing and commercializing
novel therapeutics to treat patients suffering from serious
diseases. Imara is considering development plans for
tovinontrine in heart failure with preserved ejection fraction
(HFpEF), as well as for 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
StatementsStatements 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 the Company’s plans
to discontinue the Ardent and Forte clinical trials of tovinontrine
and the Company’s future strategy, prospects and plans, including
for tovinontrine in HFpEF and for IMR-261. 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; the risk that the
Company may not be able to successfully implement its strategic
plans; the Company’s ability to advance the development of its
product candidates under the timelines it projects in current and
future clinical trials and to demonstrate in any current and future
clinical trials the requisite safety and efficacy of such product
candidates; and other factors discussed in the “Risk Factors”
section of the Company’s most recent Annual Report on Form 10-K,
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.
Media Contact:Gina NugentTen Bridge
Communications617-460-3579gina@tenbridgecommunications.com
Investor Contact:Michael
Gray617-835-4061mgray@imaratx.com
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