Hepion Pharmaceuticals, Inc. (NASDAQ:HEPA), a clinical stage
biopharmaceutical company focused on the development of therapeutic
drugs for the treatment of liver disease arising from non-alcoholic
steatohepatitis ("NASH"), today announced positive topline results
from its Phase 2a ‘AMBITION’ NASH clinical trial. All primary
endpoints of the trial were met.
AMBITION was a Phase 2a randomized,
multi-center, placebo controlled, single-blind trial designed to
investigate once daily oral administration of CRV431 at doses of 75
mg and 225 mg administered as soft gelatin capsules to presumed F2
and F3 NASH subjects for 28 days, followed by a 14-day observation
period for safety.
The primary outcome measure of the AMBITION
trial was the incidence of safety and tolerability events of CRV431
versus placebo. CRV431 at both study doses was well tolerated, and
there were no serious adverse events (“SAEs”), and the few adverse
events (“AEs”) observed were mostly mild and unrelated to study
drug.
In the AMBITION trial, CRV431 blood
concentrations after oral dosing of either 75 mg or 225 mg once
daily were in the anticipated effective range for NASH treatment.
The drug reached maximum concentrations within two hours after
dosing with an effective half-life of approximately 30 hours, which
supports once daily dosing.
It has been reported in recent literature that
reductions in serum alanine aminotransferase (“ALT”) may be used as
a surrogate measure for histologic improvement in NASH.1,2 The
AMBITION trial did not include liver biopsies, however early
indications of efficacy in the form of ALT reductions were observed
with both CRV431 dosing cohorts. The percent ALT change from
baseline to Day 28 numerically demonstrated a CRV431 versus placebo
dose-response. These declines were statistically significant from
placebo (p < 0.05) when CRV431 doses were pooled. Area-under-the
ALT-Curve (“AUC”) for ALT changes, which has been useful in
evaluating the magnitude of effect for clinical laboratory
measurements of transaminases in NASH, was also calculated. As set
out in the table below, CRV431 demonstrated decreasing ALT AUCs
with increasing dose, indicating a positive dose-response. In
addition, the 225 mg cohort ALT AUC was statistically different
from the placebo group AUC.
Test |
Placebo(n=14) |
CRV431 75 mg(n=12) |
CRV431 225 mg(n=15) |
ALT (% change) |
-6.1±13.3(mean±SD)-5.2 (median) |
-18.4±25.8 (mean±SD)*-15.9 (median) |
-21.1±21.1 (mean±SD)*-20.0 (median) |
Area-Under-the-ALT-Curve (AUC)(IU*D/L) |
1465.1 ± 810.9 |
1190.5 ± 712.1 |
859.9 ± 387.0** |
* Pooled 75 mg & 225 mg
statistically significant from placebo, p < 0.05, unpaired
t-test.**Statistically significant from placebo, p < 0.05, ANOVA
with Bonferroni Post-Hoc
“The observed changes in serum ALT at this early
timepoint, along with the safety and tolerability data are very
encouraging and suggest a potential positive impact of CRV431 on
hepatocyte health relative to placebo,” commented Stephen Harrison,
MD, Principal Investigator of the AMBITION study, Medical Director
for Pinnacle Clinical Research, San Antonio, Texas, and Visiting
Professor of Hepatology, Oxford University. “I am eagerly
anticipating additional biomarker data for this cohort and am
hopeful to see corroborating evidence of a biochemical effect.
Given the chronic nature of this disease, long-term therapy is
likely going to be needed and, therefore, a therapy that is well
tolerated, oral and once daily would be advantageous.”
“Statistical significance in a dose response on
ALT is very encouraging, suggesting a rapid drug effect. A thorough
review of literature by our group suggested that a 10% to 15%
decline in ALT in four weeks over placebo would indicate a
beneficial drug effect,” stated Patrick Mayo, Ph.D., Hepion’s SVP,
Clinical Pharmacology and Analytics. “Our clinical pharmacology
group has already developed a population
pharmacokinetic-pharmacodynamic, or PK-PD, model which predicts
CRV431 blood concentration effect on ALT reductions, which is not
usually possible at this early stage in drug development.
Additionally, preliminary transcriptomic and lipidomic analyses
further support a drug effect when CRV431 blood concentrations
exceed 800 ng/mL. This Phase 2a study confirmed CRV431 tolerability
and successfully elucidated drug dose range for the upcoming Phase
2b trial.”
“In order to embark on a phase 2b program in
NASH, these results were critical to inform us on many key
parameters for use of CRV431 in this patient population,” said Todd
Hobbs, MD, Hepion’s Chief Medical Officer. “Despite the challenges
of starting clinical research during the COVID pandemic, the team
was able to successfully complete this important trial. We look
forward to the start of the large Phase 2b ‘ASCEND-NASH’ trial
later this year, which will evaluate CRV431 in biopsy-proven NASH
subjects with advanced fibrosis.”
“CRV431 is a cyclophilin inhibitor that
represents a new approach to treating NASH,” commented Robert
Foster, PharmD, Ph.D., Hepion’s CEO. “CRV431 is extensively
extracted by the liver after oral dosing and, as such, its
potential in treating liver disease is heavily dependent on liver
function. We know that liver function declines with NASH, so it was
important to design a study to delineate the effects of NASH on the
safety, tolerability and PK of CRV431. In addition, this study gave
us an opportunity to explore the efficacy potential of CRV431 in
NASH subjects. The current findings support this potential, and we
will continue to analyze additional incoming data from this trial
which should allow us to better understand CRV431. We expect this
additional data from the AMBITION trial in the near-term and will
report it once we complete our analyses.”
1Hoofnagle, JH, et al. Aliment Pharmacol Ther.
2013; 38:134-143.
2Loomba, R. Clin Gastroenterol Hepatol. 2014;
12:1731-1732.
About Hepion Pharmaceuticals
The Company's lead drug candidate, CRV431, is a
potent inhibitor of cyclophilins, which are involved in many
disease processes. CRV431 is currently in clinical-phase
development for the treatment of NASH, with the potential to play
an important role in the overall treatment of liver disease - from
triggering events through to end-stage disease. CRV431 has been
shown to reduce liver fibrosis and hepatocellular carcinoma tumor
burden in experimental models of NASH; and has demonstrated
antiviral activities towards HBV, HCV, and HDV through several
mechanisms, in nonclinical studies.
Hepion has created a proprietary AI platform,
called AI-POWR™, which stands for Artificial
Intelligence - Precision Medicine;
Omics (including genomics, proteomics,
metabolomics, transcriptomics, and lipidomics);
World database access; and
Response and clinical outcomes. Hepion intends to
use AI-POWR™ to help identify which NASH patients will best respond
to CRV431, potentially shortening development timelines and
increasing the delta between placebo and treatment groups. In
addition to using AI-POWR™ to drive its ongoing Phase 2a NASH
program, Hepion will use the platform to identify additional
potential indications for CRV431 to expand the company's footprint
in the cyclophilin inhibition therapeutic space.
Forward Looking Statements
Certain statements in this press release are
forward-looking within the meaning of the Private Securities
Litigation Reform Act of 1995. These statements may be identified
by the use of forward-looking words such as “anticipate,”
“believe,” “forecast,” “estimated,” and “intend,” among others.
These forward-looking statements are based on Hepion
Pharmaceuticals’ current expectations and actual results could
differ materially. There are a number of factors that could cause
actual events to differ materially from those indicated by such
forward-looking statements. These factors include, but are not
limited to, substantial competition; our ability to continue as a
going concern; our need for additional financing; uncertainties of
patent protection and litigation; risks associated with delays,
increased costs and funding shortages caused by the COVID-19
pandemic; uncertainties with respect to lengthy and expensive
clinical trials, that results of earlier studies and trials may not
be predictive of future trial results; uncertainties of government
or third party payer reimbursement; limited sales and marketing
efforts and dependence upon third parties; and risks related to
failure to obtain FDA clearances or approvals and noncompliance
with FDA regulations. As with any drug candidates under
development, there are significant risks in the development,
regulatory approval, and commercialization of new products. There
are no guarantees that future clinical trials discussed in this
press release will be completed or successful, or that any product
will receive regulatory approval for any indication or prove to be
commercially successful. Hepion Pharmaceuticals does not undertake
an obligation to update or revise any forward-looking statement.
Investors should read the risk factors set forth in Hepion
Pharmaceuticals’ Form 10-K for the year ended December 31, 2020 and
other periodic reports filed with the Securities and Exchange
Commission.
For further information, please contact:
Stephen KilmerHepion Pharmaceuticals Investor RelationsDirect:
(646) 274-3580skilmer@hepionpharma.com
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