Following interim review of unblinded safety and efficacy
data, independent DSMB unanimously recommends continuation of the
global Phase 2/3 study of orally-administered opaganib for severe
COVID-19
Opaganib targets a human cell component involved in viral
replication and is therefore expected to be
effective against emerging viral variants with mutations in the
spike protein
Preliminary data from the non-powered U.S. Phase 2 study of
opaganib demonstrated safety and positive efficacy data across key
primary and secondary endpoints
TEL AVIV, Israel and
RALEIGH, N.C., Jan. 29, 2021 /PRNewswire/ -- RedHill
Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a
specialty biopharmaceutical company, today announced that the
independent Data Safety Monitoring Board (DSMB) for the global
Phase 2/3 study of opaganib[1] in patients with severe
COVID-19, unanimously recommended to continue the study following a
pre-scheduled futility review of unblinded efficacy data from the
first 135 patients treated in the study and safety data from the
first 175 patients.
"Opaganib is a novel, orally-administered sphingosine kinase-2
(SK2) inhibitor with demonstrated antiviral, anti-inflammatory, and
anti-thrombotic activity. The positive and unanimous DSMB
recommendation is a significant milestone in the progress of our
development program for COVID-19 disease. Taken together with the
positive results from the Phase 2 study, this unanimous DSMB
recommendation to continue the global Phase 2/3 study suggests we
are heading in the right direction from both a safety and efficacy
perspective," said Mark L.
Levitt, M.D., Ph.D., Medical Director at RedHill. "This
is a particularly difficult time in the fight against the pandemic,
with viral mutations increasing infection rates and impacting many
aspects of society's response to the pandemic. The need for
effective therapeutics is clear. Opaganib's mechanism of action
targets the human host cell component SK2, which is involved in
both viral replication inside the cell and downstream
inflammatory/immune responses. This means that opaganib is expected
to maintain its activity irrespective of the worrisome mutations in
SARS-CoV-2 spike protein. These mutations underscore the potential
of SARS-CoV-2 to develop resistance to direct anti-viral mAbs, and
to potentially impact vaccine effectiveness. This is an important
advantage of opaganib in the face of the growing multitude of viral
strains and provides the promise of a much-needed treatment option
to help get patients off oxygen and out of hospital."
This positive DSMB futility review, which is suggestive that the
global Phase 2/3 study is progressing as expected, adds to positive
top-line safety and efficacy data from the U.S. Phase 2 study, in
which opaganib demonstrated 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.
The Phase 2 data also showed no material safety differences between
the opaganib and placebo treatment arms - further adding to the
growing safety database for opaganib. Full analysis of the Phase 2
data, including viral and inflammatory biomarker analyses, baseline
risk factors and standard-of-care background therapy
stratification, is expected in the coming weeks and is planned to
be provided for peer review.
In-line with rapidly evolving clinical practice and guidelines
for treatment of hospitalized COVID-19 patients, which aim to
minimize patient intubation and mechanical ventilation, the primary
endpoint of the global Phase 2/3 study is now the proportion of
patients reaching room air (no longer requiring oxygen
supplementation) by Day 14, previously a key secondary endpoint.
Intubation and mechanical ventilation remains as a secondary
endpoint. Correspondingly, a blind resizing of the study is
planned, to approximately 460 patients. There are approximately 30
study sites in 7 countries with additional sites and countries
being added in the coming days and weeks. Top-line data, and
potential global emergency use authorization applications are
expected in the second quarter of 2021.
About Opaganib (Yeliva®, ABC294640)
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 anti-inflammatory, antiviral
and anti-thrombotic 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. Opaganib also
demonstrated reduced blood clot length, weight and total thrombus
score in a preclinical model of Acquired Respiratory Distress
Syndrome. 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[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
development programs include: (i) RHB-204, with an
ongoing Phase 3 study for pulmonary nontuberculous mycobacteria
(NTM) disease; (ii) opaganib (Yeliva®,
ABC294640), 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-107
(upamostat), a serine protease inhibitor with a planned
Phase 2/3 study in symptomatic COVID-19 and targeting multiple
other cancer and inflammatory gastrointestinal diseases; (iv)
RHB-104, with positive results from a first Phase 3 study
for Crohn's disease; (v) 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; and (vi) RHB-106, an
encapsulated bowel preparation. More information about the Company
is available at www.redhillbio.com /
https://twitter.com/RedHillBio.
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 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 2/3 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 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.
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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