TEL AVIV, Israel and
RALEIGH, N.C., Dec. 31, 2020 /PRNewswire/ -- RedHill
Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a
specialty biopharmaceutical company, today announced that
preliminary top-line data from its U.S. Phase 2 study with
orally-administered opaganib (Yeliva®,
ABC294640)[1] in patients hospitalized with COVID-19
pneumonia demonstrated positive safety and efficacy signals.
The randomized, double-blind, placebo-controlled U.S. Phase 2
proof-of-concept study with opaganib (NCT04414618) enrolled 40
patients requiring oxygen support. The study was not powered for
statistical significance and aimed to evaluate safety and identify
preliminary signs of activity. Patients in the study were
randomized at a 1:1 ratio to receive either opaganib or placebo on
top of standard-of-care (SoC) and were followed up for up to 42
days post treatment initiation.
- Top-line results from the study found opaganib to be safe, with
no material safety differences between the opaganib and placebo
treatment arms. Overall, fewer patients suffered from serious
adverse events (SAEs) in the opaganib treatment arm than in the
placebo arm. In this small sample size, there were few events of
intubation or fatality and these were balanced between the two
arms.
- The opaganib-treated arm demonstrated a consistent trend of
greater improvement in reducing oxygen requirement by end of
treatment on Day 14 across key primary and secondary efficacy
outcomes, correlating with clinical improvement as defined by the
World Health Organization (WHO) ordinal scale:
- A greater improvement in the proportion of patients reaching room
air and no longer requiring oxygen support by Day 14 vs. the
control arm (52.6% vs. 22.2%).
- A greater improvement in the proportion of patients with 50%
reduction in supplemental oxygen by day 14 vs. the control arm
(89.5% vs. 66.7%).
- A higher proportion of patients discharged by Day 14 vs. the
control arm (73.7% vs. 55.6%).
- A greater reduction from baseline of the median total oxygen
requirement (AUC) over 14 days vs. the control arm (68.0% vs.
46.7%).
Full analysis of the data, including viral and inflammatory
biomarker analyses, baseline risk factors and SoC background
therapy stratifications, is expected in the coming weeks. The
Company will provide the data for peer review when available.
"We are pleased with these encouraging top-line results from our
exploratory Phase 2 study which confirm opaganib's safety and
demonstrate promising signals of activity when treating patients
with COVID-19 and who require oxygen support. These preliminary
results support our ongoing global Phase 2/3 study in severe
COVID-19 pneumonia, which is expected to read out in Q1/2021. We
continue to work diligently to compile a robust data set to support
potential filing of global emergency use applications," said
Mark L. Levitt, MD, Ph.D., Medical
Director at RedHill.
Gilead Raday, RedHill's Chief
Operating Officer, added: "Opaganib has a unique dual mode of
action that is both anti-inflammatory and antiviral – acting on
both the cause and the effects of COVID-19. Opaganib targets
sphingosine kinase-2, a human cell component involved in viral
replication and not the virus itself. The mounting evidence of new
SARS-CoV-2 mutations emerging globally underscores the importance
of this unique mechanism, which potentially minimizes the risk of
viral resistance to therapy. The trends of patient improvement
shown by the preliminary top-line data support the ongoing Phase
2/3 study with opaganib, which will provide a more in-depth
understanding of opaganib's activity."
The efficacy of opaganib in severe COVID-19 pneumonia is being
further explored in an ongoing global Phase 2/3 study and is
expected to report top-line data in the first quarter of 2021. This
study (NCT04467840) is being conducted across approximately 30
clinical sites in several countries and is on track to enroll up to
270 patients. The study has undergone two unblinded reviews of
safety data by an independent Data and Safety Monitoring Board
(DSMB), with unanimous recommendations to continue the study. An
interim DSMB futility analysis will be conducted in the coming
weeks, evaluating data from the first 135 subjects that have
reached the primary endpoint.
The top-line results from the U.S. Phase 2 study of opaganib in
patients hospitalized with COVID-19 pneumonia are preliminary and
were provided to the Company by an independent third-party
following an initial independent analysis and remain subject to
additional review and analysis. Such review and analysis may result
in findings inconsistent with the results disclosed in this release
and may not be replicated in future studies.
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 as a
treatment for COVID-19 pneumonia in a global Phase 2/3 study and
has demonstrated positive safety and efficacy signals in
preliminary top-line data from a U.S. Phase 2 study.
Preclinical data have demonstrated both anti-inflammatory and
antiviral activities of opaganib, with the potential to ameliorate
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[2] 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.
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[3],
Talicia® for the treatment of
Helicobacter pylori (H. pylori) infection in
adults[4], and Aemcolo® for the
treatment of travelers' diarrhea in adults[5]. RedHill's
key clinical late-stage investigational development programs
include: (i) RHB-204, with an ongoing 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 a full analysis of the data from the U.S. Phase 2
trial evaluating opaganib, the timing of potential emergency use
applications for opaganib and the timing of reporting of top-line
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 top-line data from the
Phase 2/2 study and in receiving data to support emergency use
applications or in making such emergency use applications, if at
all; the risk that the full analysis of data from the U.S. Phase 2
clinical study evaluating opaganib will be delayed or will differ
from the preliminary data; 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 top-line 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.
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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
1. Opaganib is an investigational new drug, not
available for commercial distribution.
2. 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.
3. Full prescribing information for
Movantik® (naloxegol) is available at:
www.Movantik.com.
4. Full prescribing information for Talicia®
(omeprazole magnesium, amoxicillin and rifabutin) is available at:
www.Talicia.com.
5. Full prescribing information for
Aemcolo® (rifamycin) is available at:
www.Aemcolo.com.
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SOURCE RedHill Biopharma Ltd.