All Endpoints Met in Hepion Pharmaceuticals’ Drug-Drug Interaction Study with CRV431
September 29 2021 - 9:00AM
Hepion Pharmaceuticals, Inc. (NASDAQ:HEPA), a clinical stage
biopharmaceutical company focused on Artificial Intelligence
(“AI”)-driven therapeutic drug development for the treatment of
non-alcoholic steatohepatitis (“NASH”) and liver disease, today
announced results from a Drug-Drug Interaction (‘DDI’) study with
its lead drug candidate, CRV431.
CRV431 targets several isoforms of cyclophilins
which comprise a family of enzymes involved in processes including
collagen production, inflammation, cell injury, cell death, and
protein folding. Attenuation of the activities of this
multifunctional enzyme family represents a novel approach to the
treatment of NASH.
The randomized, open label DDI study was
conducted in healthy volunteers (n = 24) to determine if single or
multiple oral doses of ketoconazole (400 mg) influence the
pharmacokinetics (‘PK’) of CRV431 (75 mg) and its major
metabolites. The study also examined if single or multiple once
daily oral doses of CRV431 effected the PK of midazolam (2 mg IV)
and its metabolite, 1-hydroxymethyl midazolam. Additionally, the
safety and tolerability of CRV431 when administered concomitantly
with either ketoconazole or midazolam was assessed. Each study
subject participated in both parts of the two-staged trial.
As expected, following five daily oral doses of
ketoconazole, the maximum blood concentration (‘Cmax’) of CRV431
increased approximately five-fold, while the exposure, as measured
by the area-under-the-curve from time of dosing to 24 hours
(‘AUC0-24’), increased almost four-fold. When CRV431 was dosed with
midazolam, the exposures of midazolam and 1-hydroxymethyl midazolam
were not significantly altered. However, both the Cmax and AUC0-24
of CRV431 were increased by approximately two-fold.
“DDI studies are important in determining
possible safety liabilities during drug development and are
standard in the industry,” commented Patrick Mayo, PhD, Hepion’s
SVP, Clinical Pharmacology & Analytics. “CRV431 is metabolized
by enzymes called ‘cytochrome P450’. In particular, cytochromes
P450 3A4 and 3A5, which are abundant in the gut and liver, play an
important role in the metabolism of many currently marketed drugs,
and are the main metabolic pathway for CRV431. This DDI study
demonstrated that a potent inhibitor of CYP3A4, ketoconazole,
raised CRV431 exposures by approximately five-fold while remaining
safe and well tolerated, confirming the safety of CRV431 even in
the presence of drug inhibitors. The minimal interaction with
midazolam demonstrates that CRV431 can be safely administered with
other drugs metabolized through this pathway. These findings open
the door for the safe use of myriad drug combinations for the
treatment of co-morbidities, including diabetes and high
cholesterol in NASH patients. This study also demonstrated that we
need not have any concerns regarding potential drug interactions
and safety. The observed PK profile was as we expected with this
DDI, further reassuring us of the overall safety profile of
CRV431.”
Todd Hobbs, MD, Hepion’s Chief Medical Officer
added, “Patients diagnosed with fatty liver disease and/or NASH are
commonly prescribed multiple life-long drug therapies to manage
associated medical conditions, such as diabetes and hypertension.
And typically, the number of medications prescribed to NASH
patients increases with increasing severity of disease, such that
those with advanced fibrosis and cirrhosis are at greatest risk for
drug interactions as a result of polypharmacy. In fact, a study
characterizing polypharmacy determined that NASH patients received,
on average, seven medications and patients with cirrhosis received
an average of 11 medications.1 It is, therefore, vitally important
to fully understand how the disposition of CRV431 may potentially
be altered by other drugs or how CRV431 might alter the PK and
performance of co-administered drugs. This knowledge will not only
be valuable when designing our future clinical trials but could
also ultimately help guide the use of CRV431 in a commercial
setting.”
1https://www.targetrwe.com/images/1118/target_nash_polypharmacy.pdf
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 NASH clinical
development program, Hepion intends to 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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