Enrollment completed in the U.S. Phase 2 study evaluating
opaganib's safety and initial efficacy signal in 40 hospitalized
patients with severe COVID-19 pneumonia
A parallel global Phase 2/3 study with orally administered
opaganib for severe COVID-19 is approximately 50% enrolled - on
track to enroll all 270 patients and report topline data in
Q1/2021
Potential emergency use applications expected as early as
Q1/2021
Opaganib's unique dual anti-inflammatory and antiviral
activity acts on the cause and effect of COVID-19 disease with host
cell targeting, minimizing potential for resistance due to viral
mutations
TEL AVIV, Israel and
RALEIGH, NC, Nov. 16, 2020 /PRNewswire/ -- RedHill Biopharma
Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty
biopharmaceutical company, today announced that the U.S. Phase 2
study with opaganib (Yeliva®, ABC294640)[1] in patients
hospitalized with severe COVID-19 pneumonia has completed
enrollment of the last patient in the study. The study is not
powered for statistical significance. Topline data is expected in
the coming weeks.
"Completing enrollment in this U.S. Phase 2 study of orally
administered opaganib in severe COVID-19 is a key milestone,
indicating that we are just weeks away from important safety data
and increased understanding of the potential of opaganib. In
parallel, our global Phase 2/3 study is approximately 50% enrolled
and is expected to undergo its first pre-planned safety analysis in
the coming days and report topline data in the first quarter of
2021. We are compiling a robust data set to support the planned
emergency use applications, expected as early as next quarter,
subject to study success." said Mark L.
Levitt, MD, Ph.D., Medical Director at RedHill.
"Opaganib has a demonstrated unique dual mode of action that is
both anti-inflammatory and antiviral – acting on the cause and the
effect of COVID-19. Moreover, opaganib acts on a host cell
component involved in viral replication and not the virus itself,
which could minimize issues of resistance due to emergence of viral
mutations. In light of the encouraging data from patients with
severe COVID-19 treated with opaganib under compassionate
use[2] and the potent anti-SARS-CoV-2 activity that
opaganib has demonstrated in vitro, we are excited to see
the data from the U.S. Phase 2 study and look to rapidly complete
the global Phase 2/3 development program for opaganib toward
potential emergency use authorization applications."
The randomized, double-blind, placebo-controlled Phase 2 study
with opaganib (NCT04414618) enrolled 40 patients in clinical sites
across the U.S. The study is not powered for statistical
significance and is focused on safety evaluation and identifying a
signal of efficacy. Patients in the study were randomized at a
1:1 ratio to receive either opaganib or placebo on top of
standard-of-care. The primary objective of the study is to evaluate
the reduction in total oxygen requirement over the course of
treatment for up to 14 days. Secondary endpoints include time to
50% reduction in oxygen requirements, the proportion of patients
without fever at Day 14, and proportion with negative nasal swabs
at Day 14.
In parallel, the global Phase 2/3 study with opaganib in
patients with severe COVID-19 pneumonia (NCT04467840) is
approximately 50% enrolled and is expected to report topline data
in the first quarter of 2021. The study is being conducted across
21 clinical sites and is on track to enroll up to 270 patients. A
first unblinded review of safety data from the first 70 patients
enrolled in the study by an independent Data and Safety Monitoring
Board (DSMB) is expected in the coming days. An unblinded futility
interim analysis will be conducted by the DSMB in the coming weeks,
evaluating data from the first 135 subjects that have reached the
primary endpoint. This study is focused on, and powered for,
efficacy evaluation. The study has been approved in the UK,
Italy, Russia, Mexico, Brazil and Israel, with further expansion
ongoing.
The clinical studies with opaganib are intended to support
potential emergency use applications as early as the first quarter
of 2021, subject to positive results.
About Opaganib (ABC294640, Yeliva®)
Opaganib, a new chemical entity, is a proprietary,
first-in-class, orally administered, sphingosine kinase-2 (SK2)
selective inhibitor with demonstrated dual anti-inflammatory and
antiviral activity that targets a host cell component of viral
replication, potentially minimizing the likelihood of viral
resistance. Opaganib has also shown anticancer activity and has the
potential to target multiple oncology, viral, inflammatory, and
gastrointestinal indications.
Opaganib received Orphan Drug designation from the U.S. FDA
for the treatment of cholangiocarcinoma and is being evaluated in a
Phase 2a study in advanced cholangiocarcinoma and in a Phase 2
study in prostate cancer. Opaganib is also being evaluated in a
global Phase 2/3 study and a U.S. Phase 2 study for the treatment
of COVID-19.
Preclinical data have demonstrated both anti-inflammatory and
antiviral activities of opaganib, with the potential to reduce
inflammatory lung disorders, such as pneumonia, and mitigate
pulmonary fibrotic damage. Opaganib demonstrated potent antiviral
activity against SARS-CoV-2, the virus that causes
COVID-19, completely inhibiting viral replication in an in
vitro model of human lung bronchial tissue. Additionally,
preclinical in vivo studies[3] have
demonstrated that opaganib decreased fatality rates from influenza
virus infection and ameliorated Pseudomonas
aeruginosa-induced lung injury by reducing the levels of IL-6
and TNF-alpha in bronchoalveolar lavage fluids.
Opaganib was originally developed by U.S.-based Apogee
Biotechnology Corp. and completed multiple successful preclinical
studies in oncology, inflammation, GI, and radioprotection models,
as well as a Phase 1 clinical study in cancer patients with
advanced solid tumors and an additional Phase 1 study in multiple
myeloma.
Under a compassionate use program, COVID-19 patients (as
classified by the WHO ordinal scale) were treated with opaganib in
a leading hospital in Israel. Data
from the treatment of these first patients with severe COVID-19
with opaganib have been published[2]. Analysis of
treatment outcomes suggested substantial benefit to patients
treated with opaganib under compassionate use in both clinical
outcomes and inflammatory markers as compared to a retrospective
matched case-control group from the same hospital. All patients in
the opaganib-treated group were discharged from hospital on room
air without requiring intubation and mechanical ventilation,
whereas 33% of the matched case-control group required intubation
and mechanical ventilation. Median time to weaning from high-flow
nasal cannula was reduced to 10 days in the opaganib-treated group,
as compared to 15 days in the matched case-control group.
The development of opaganib has been supported by grants
and contracts from U.S. federal and state government agencies
awarded to Apogee Biotechnology Corp., including from the NCI,
BARDA, the U.S. Department of Defense and the FDA Office of Orphan
Products Development.
The ongoing studies with opaganib are registered
on www.ClinicalTrials.gov, a web-based service by the U.S.
National Institute of Health, which provides public access to
information on publicly and privately supported clinical
studies.
About RedHill Biopharma
RedHill Biopharma Ltd. (Nasdaq: RDHL) is a specialty
biopharmaceutical company primarily focused on gastrointestinal and
infectious diseases. RedHill promotes the gastrointestinal drugs,
Movantik® for opioid-induced constipation in
adults with non-cancer pain[4],
Talicia® for the treatment of Helicobacter pylori
(H. pylori) infection in adults[5], and
Aemcolo® for the treatment of travelers' diarrhea
in adults[6]. RedHill's key clinical
late-stage investigational development programs include: (i)
RHB-204, with a planned Phase 3 study for pulmonary
nontuberculous mycobacteria (NTM) infections; (ii) opaganib
(Yeliva®), a first-in-class SK2
selective inhibitor targeting multiple indications with a Phase 2/3
program for COVID-19 and Phase 2 studies for prostate cancer and
cholangiocarcinoma ongoing; (iii) RHB-104, with positive
results from a first Phase 3 study for Crohn's disease; (iv)
RHB-102 (Bekinda®), with positive results
from a Phase 3 study for acute gastroenteritis and gastritis and
positive results from a Phase 2 study for IBS-D; (v)
RHB-107, a Phase 2-stage first-in-class, serine
protease inhibitor, targeting cancer and inflammatory
gastrointestinal diseases and is also being evaluated for COVID-19
and (vi) RHB-106, an encapsulated bowel preparation.
More information about the Company is available at
www.redhillbio.com.
This press release contains "forward-looking statements"
within the meaning of the Private Securities Litigation Reform Act
of 1995. Such statements may be preceded by the words "intends,"
"may," "will," "plans," "expects," "anticipates," "projects,"
"predicts," "estimates," "aims," "believes," "hopes," "potential"
or similar words and includes statements regarding the timing of
the reporting of data from the U.S. Phase 2 trial evaluating
opaganib, the timing of potential emergency use applications of
opaganib. Reporting of topline data, safety analysis and of
unblinded futility interim analysis for the global Phase 2/3 study
with opaganib. Forward-looking statements are based on certain
assumptions and are subject to various known and unknown risks and
uncertainties, many of which are beyond the Company's control and
cannot be predicted or quantified, and consequently, actual results
may differ materially from those expressed or implied by such
forward-looking statements. Such risks and uncertainties include,
without limitation, the risk that the Company's Phase 2/3 study
evaluating opaganib will not be successful; the risk of a delay in
receiving data to support emergency use applications or in making
such emergency use applications, if at all; the risk that the U.S.
Phase 2 clinical study evaluating opaganib will not be successful
and the risk that the reporting of data from this clinical study
will be delayed if at all; the risk that the Company will not
initiate the Phase 2/3 study for opaganib in certain geographies,
will not expand this study to additional countries and that it will
not be successful and that enrollment, reporting of topline data,
safety analysis and/or unblinded futility interim analysis will be
delayed; the risk that other COVID-19 patients treated with
opaganib will not show any clinical improvement; the development
risks of early-stage discovery efforts for a disease that is still
little understood, including difficulty in assessing the efficacy
of opaganib for the treatment of COVID-19, if at all; intense
competition from other companies developing potential treatments
and vaccines for COVID-19; the effect of a potential occurrence of
patients suffering serious adverse events using opaganib under
compassionate use programs, as well as risks and uncertainties
associated with (i) the initiation, timing, progress and results of
the Company's research, manufacturing, preclinical studies,
clinical trials, and other therapeutic candidate development
efforts, and the timing of the commercial launch of its commercial
products and ones it may acquire or develop in the future; (ii) the
Company's ability to advance its therapeutic candidates into
clinical trials or to successfully complete its preclinical studies
or clinical trials (iii) the extent and number and type of
additional studies that the Company may be required to conduct and
the Company's receipt of regulatory approvals for its therapeutic
candidates, and the timing of other regulatory filings, approvals
and feedback; (iv) the manufacturing, clinical development,
commercialization, and market acceptance of the Company's
therapeutic candidates and Talicia®; (v) the Company's
ability to successfully commercialize and promote
Movantik®, Talicia® and Aemcolo®;
(vi) the Company's ability to establish and maintain corporate
collaborations; (vii) the Company's ability to acquire products
approved for marketing in the U.S. that achieve commercial success
and build and sustain its own marketing and commercialization
capabilities; (viii) the interpretation of the properties and
characteristics of the Company's therapeutic candidates and the
results obtained with its therapeutic candidates in research,
preclinical studies or clinical trials; (ix) the implementation of
the Company's business model, strategic plans for its business and
therapeutic candidates; (x) the scope of protection the Company is
able to establish and maintain for intellectual property rights
covering its therapeutic candidates and commercial products and its
ability to operate its business without infringing the intellectual
property rights of others; (xi) parties from whom the Company
licenses its intellectual property defaulting in their obligations
to the Company; (xii) estimates of the Company's expenses, future
revenues, capital requirements and needs for additional financing;
(xiii) the effect of patients suffering adverse events using
investigative drugs under the Company's Expanded Access Program;
and (xiv) competition from other companies and technologies within
the Company's industry. More detailed information about the Company
and the risk factors that may affect the realization of
forward-looking statements is set forth in the Company's filings
with the Securities and Exchange Commission (SEC), including the
Company's Annual Report on Form 20-F filed with the SEC on
March 4, 2020. All forward-looking
statements included in this press release are made only as of the
date of this press release. The Company assumes no obligation to
update any written or oral forward-looking statement, whether as a
result of new information, future events or otherwise unless
required by law.
References:
[1] Opaganib is an investigational new drug, not available for
commercial distribution.
[2] Kurd R, Ben-Chetrit E, Karameh H, Bar-Meir M, Compassionate
Use of Opaganib For Patients with Severe COVID-19. medRxiv
2020.06.20.20099010; doi:
https://doi.org/10.1101/2020.06.20.20099010
[3] Xia C. et al. Transient inhibition of sphingosine kinases
confers protection to influenza A virus infected mice. Antiviral
Res. 2018 Oct; 158:171-177. Ebenezer DL et al. Pseudomonas
aeruginosa stimulates nuclear sphingosine-1-phosphate
generation and epigenetic regulation of lung inflammatory injury.
Thorax. 2019 Jun;74(6):579-591.
[4] Full prescribing information for Movantik®
(naloxegol) is available at: www.Movantik.com.
[5] Full prescribing information for Talicia®
(omeprazole magnesium, amoxicillin and rifabutin) is available at:
www.Talicia.com.
[6] Full prescribing information for Aemcolo®
(rifamycin) is available at: www.Aemcolo.com.
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Company
contact:
Adi Frish
Chief Corporate &
Business Development Officer
RedHill
Biopharma
+972-54-6543-112
adi@redhillbio.com
|
Media contact
(U.S.):
Bryan
Gibbs
Vice
President
Finn
Partners
+1 212 529
2236
bryan.gibbs@finnpartners.com
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