SAN DIEGO, July 16, 2020 /PRNewswire/ -- Heron Therapeutics,
Inc. (Nasdaq: HRTX), a commercial-stage biotechnology company
focused on improving the lives of patients by developing
best-in-class treatments to address some of the most important
unmet patient needs, today announced the initiation of the GUARDS-1
Study, a Phase 2 clinical study evaluating CINVANTI (aprepitant)
injectable emulsion in early hospitalized patients with Coronavirus
Disease 2019 (COVID-19). The study initiation follows clearance
from the U.S. Food and Drug Administration (FDA) of Heron's
Investigational New Drug application for CINVANTI for the treatment
of COVID-19.
CINVANTI is an intravenous formulation of aprepitant, a
substance P/neurokinin-1 (NK1) receptor antagonist (RA)
approved for use for the prevention of chemotherapy-induced nausea
and vomiting in patients with cancer. Substance P, and its receptor
NK1, is distributed throughout the body in the cells of
many tissues and organs, including the lungs. COVID-19, which is
caused by severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2), is associated with lower respiratory tract
inflammation that often progresses to Acute Respiratory Distress
Syndrome (ARDS). ARDS is associated with high mortality.
Heron's rationale for the investigation of CINVANTI for the
treatment of COVID-19 is based on multiple potential mechanisms for
activity. Suppressing the cytokine storm could be a crucial step to
prevent the clinical deterioration of patients with COVID-19.
Administration of aprepitant injectable emulsion to these patients
is expected to decrease the production and release of inflammatory
cytokines mediated by the binding of substance P to
NK1 receptors, which could prevent the progression
of lung injury to ARDS. A hallmark of COVID-19 is a non-productive
neurogenic cough, likely due to the increased susceptibility of
lung tissue to neurogenic inflammation caused by the disease.
Recent studies have demonstrated that administration of oral
aprepitant resulted in significantly decreased severity of cough in
patients with neurogenic cough associated with advanced lung
cancer. Additionally, aprepitant may have direct antiviral
activity. Using a computational screening approach, aprepitant was
found to have the ability to form hydrogen bonds to key residues
within the binding pocket of the main protease of SARS-CoV-2, which
is a key enzyme required for replication. CINVANTI is approved for
administration as a 2-minute intravenous injection. For these
potential benefits, the plasma concentrations of aprepitant
produced with the 2-minute intravenous injection of CINVANTI could
provide a unique advantage over other methods of
administration.
GUARDS-1, also referred to as Study HTX-019-202, is a
randomized, placebo-controlled, double-blinded, Phase 2 study
designed to investigate the efficacy and safety of adding daily
dosing of CINVANTI for 14 days as a 2-minute intravenous
injection to standard of care to reduce mortality and the need
for assisted ventilation in early hospitalized adult patients with
a confirmed SARS–CoV-2 infection. The use of remdesivir through the
Emergency Use Authorization and dexamethasone as standard of care
are both permitted in the study. The study will include up to
approximately 100 adult patients who are hospitalized with a
confirmed SARS-CoV-2 infection less than 24 hours prior to
randomization. Importantly, the participating clinical study sites
have a high concentration of racial and ethnic minority patients
affected by COVID-19.
"The COVID-19 pandemic has impacted millions of Americans. With
the rate of hospitalization increasing in many states, many
intensive care units (ICUs) are reaching capacity. Identifying
marketed drugs that may keep more patients out of the ICUs is the
most efficient way to impact the current crisis," said Barry Quart,
Pharm.D., President and Chief Executive Officer of Heron. "With an
existing commercial supply chain for CINVANTI and a positive safety
profile in over 1 million single-dose administrations to patients
with cancer who also receive dexamethasone, we are hopeful that we
can deliver an effective therapeutic option for patients with
COVID-19."
About CINVANTI (Aprepitant) Injectable Emulsion
CINVANTI, in combination with other antiemetic agents, is
indicated in adults for the prevention of acute and delayed nausea
and vomiting associated with initial and repeat courses of highly
emetogenic cancer chemotherapy (HEC) including high-dose cisplatin
as a single-dose regimen, delayed nausea and vomiting associated
with initial and repeat courses of moderately emetogenic cancer
chemotherapy (MEC) as a single-dose regimen, and nausea and
vomiting associated with initial and repeat courses of MEC as a
3-day regimen. CINVANTI is an IV formulation of aprepitant, a
substance P/neurokinin-1 (NK1) receptor antagonist (RA).
CINVANTI is the first IV formulation to directly deliver
aprepitant, the active ingredient in
EMEND® capsules. Aprepitant (including its prodrug,
fosaprepitant) is the only single-agent NK1 RA to
significantly reduce nausea and vomiting in both the acute phase
(0–24 hours after chemotherapy) and the delayed phase (24–120 hours
after chemotherapy). The FDA-approved dosing administration
included in the United States prescribing information for
CINVANTI is a 30-minute IV infusion or a 2-minute IV injection.
CINVANTI is under investigation for the treatment of COVID-19 as
a daily 2-minute IV injection when added to the current standard of
care.
Please see full prescribing information at www.CINVANTI.com.
IMPORTANT SAFETY INFORMATION
Contraindications
CINVANTI is contraindicated in patients with hypersensitivity to
any of the components of CINVANTI.
Concurrent use of pimozide with CINVANTI is contraindicated.
Warnings and Precautions
Clinically Significant CYP3A4 Drug Interactions
Aprepitant is a substrate, weak-to-moderate (dose-dependent)
inhibitor, and an inducer of CYP3A4.
- Use of CINVANTI with other drugs that are CYP3A4 substrates may
result in increased plasma concentration of the concomitant
drug.
-
- Use of pimozide with CINVANTI is contraindicated due to the
risk of significantly increased plasma concentrations of pimozide,
potentially resulting in prolongation of the QT interval, a known
adverse reaction of pimozide.
- Use of CINVANTI with strong or moderate CYP3A4 inhibitors
(e.g., ketoconazole, diltiazem) may increase plasma
concentrations of aprepitant and result in an increased risk of
adverse reactions related to CINVANTI.
- Use of CINVANTI with strong CYP3A4 inducers (e.g.,
rifampin) may result in a reduction in aprepitant plasma
concentrations and decreased efficacy of CINVANTI.
Hypersensitivity Reactions
Serious hypersensitivity reactions, including anaphylaxis,
during or soon after administration of CINVANTI have occurred.
Symptoms including dyspnea, eye swelling, flushing, pruritus, and
wheezing have been reported. If hypersensitivity reactions occur,
discontinue CINVANTI. Do not reinitiate CINVANTI in patients who
experience these symptoms with previous use.
Decrease in INR with Concomitant Warfarin
Co-administration of CINVANTI with warfarin, a CYP2C9 substrate,
may result in a clinically significant decrease in the
International Normalized Ratio (INR) of prothrombin time. Monitor
the INR in patients on chronic warfarin therapy in the 2-week
period, particularly at 7 to 10 days, following initiation of
CINVANTI with each chemotherapy cycle.
Risk of Reduced Efficacy of Hormonal Contraceptives
The efficacy of hormonal contraceptives may be reduced during
administration of and for 28 days following the last dose of
CINVANTI. Advise patients to use effective alternative or back-up
methods of non-hormonal contraception during treatment with
CINVANTI and for 1 month following administration of CINVANTI or
oral aprepitant, whichever is administered last.
Use in Specific Populations
Avoid use of CINVANTI in pregnant women as alcohol is an
inactive ingredient for CINVANTI. There is no safe level of alcohol
exposure in pregnancy.
Adverse Reactions
The most common adverse reactions are:
- Single-dose fosaprepitant with MEC (≥2%): fatigue, diarrhea,
neutropenia, asthenia, anemia, peripheral neuropathy, leukopenia,
dyspepsia, urinary tract infection, pain in extremity.
- 3-day oral aprepitant with MEC (≥1% and greater than standard
therapy): fatigue and eructation.
- Single-dose fosaprepitant with HEC: generally similar to 3-day
oral aprepitant. In addition, infusion site reactions (3%)
occurred.
- Single-dose CINVANTI (≥2%): headache and fatigue. The safety
profile of CINVANTI in healthy subjects who received a single
2-minute injection was similar to that seen with a 30-minute
infusion.
About Heron Therapeutics, Inc.
Heron Therapeutics, Inc. is a commercial-stage biotechnology
company focused on improving the lives of patients by developing
best-in-class treatments to address some of the most important
unmet patient needs. Heron is developing novel, patient-focused
solutions that apply its innovative science and technologies to
already-approved pharmacological agents for patients suffering from
pain or cancer.
For more information, visit www.herontx.com.
Forward-looking Statements
This news release contains "forward-looking statements" as
defined by the Private Securities Litigation Reform Act of 1995.
Heron cautions readers that forward-looking statements are based on
management's expectations and assumptions as of the date of this
news release and are subject to certain risks and uncertainties
that could cause actual results to differ materially, including,
but not limited to, those associated with: the timing and results
of the studies for the HTX-019-202 development program; the
potential market opportunity for HTX-019-202; and other risks and
uncertainties identified in the Company's filings with
the U.S. Securities and Exchange Commission. Forward-looking
statements reflect our analysis only on their stated date, and
Heron takes no obligation to update or revise these statements
except as may be required by law.
Investor Relations and Media Contact:
David Szekeres
Chief Legal, Business and Administrative Officer
Heron Therapeutics, Inc.
dszekeres@herontx.com
858-251-4447
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SOURCE Heron Therapeutics, Inc.