Country for PR: United Kingdom
Contributor: PR Newswire Europe
Tuesday, December 22 2020 - 23:41
RedHill's Phase 2/3 COVID-19 Study of Opaganib Passes Second DSMB with Unanimous Recommendation to Continue
TEL AVIV, Israel and RALEIGH, N.C., Dec. 22, 2020 /PRNewswire-AsiaNet/ --

Independent DSMB unanimously recommends continuation of the global Phase 2/3 
study of orally-administered opaganib in severe COVID-19 based on review of 
unblinded safety data from 155 treated patients 

Top-line data from the 270-patient global Phase 2/3 COVID-19 study expected 

Top-line data from the 40-patient U.S. Phase 2 study of opaganib in severe 
COVID-19 expected in the coming days; this non-powered study was designed to 
evaluate safety and potential identification of preliminary efficacy signals in 
support of the global Phase 2/3 study of opaganib

Opaganib potentially minimizes likelihood of resistance due to viral mutations 
by targeting a human cell component involved in viral replication

RedHill Biopharma Ltd. [ ] (Nasdaq: RDHL) 
("RedHill" or the "Company"), a specialty biopharmaceutical company, today 
announced that the global Phase 2/3 study with orally-administered opaganib 
(Yeliva®, ABC294640)[1] in patients hospitalized with severe COVID-19 pneumonia 
has received a second unanimous recommendation to continue, following a second 
independent Data Safety Monitoring Board (DSMB) safety review. The DSMB's 
recommendation is based on an analysis of unblinded safety data from the first 
155 patients treated for 14 days. 

"This second unanimous independent DSMB recommendation to continue the global 
Phase 2/3 study of opaganib in patients with severe COVID-19 confirms the 
safety of opaganib and means we can continue to focus on completing enrollment 
for this study as rapidly as possible, with a view to having top-line data in 
the first quarter of 2021. If successful, we expect to make subsequent global 
emergency use applications the same quarter," said Mark L. Levitt, M.D., Ph.D., 
Medical Director at RedHill. 

Enrollment in the 270-patient global Phase 2/3 study of orally-administered 
opaganib in hospitalized patients with severe COVID-19 pneumonia (NCT04467840) 
  is more than 60% complete, and is on track to deliver top-line data in the 
first quarter of 2021. This study is focused on and powered for efficacy 
evaluation. A pre-scheduled, 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.

The parallel U.S. Phase 2 study with opaganib (NCT04414618) 
 has completed enrollment of all 40 subjects, with top-line data expected by 
year's end. This study is not powered for efficacy and is focused on safety 
evaluation and potential identification of preliminary efficacy signals. 

Opaganib is a novel, orally-administered, sphingosine kinase-2 (SK2) selective 
inhibitor with a preclinically demonstrated triple-action mechanism that 
inhibits viral replication, reduces hyper-immune inflammatory response and 
diminishes ARDS-related thrombosis (blood clots) – a dangerous complication of 
COVID-19 disease – in effect acting on the cause and effect of COVID-19 
disease. Opaganib's target is a human host cell component involved in viral 
replication, potentially minimizing the likelihood of resistance due to viral 

About Opaganib (ABC294640, Yeliva®)
Opaganib, a new chemical entity, is a proprietary, first-in-class, 
orally-administered, sphingosine kinase-2 (SK2) selective inhibitor with a 
demonstrated unique triple-action effect on the pathophysiological processes 
associated with COVID-19 disease, that targets a host cell component, 
potentially minimizing the likelihood for resistance due to viral mutations. 
Opaganib has also shown anticancer activity and has the potential to target 
multiple oncology, viral, inflammatory and gastrointestinal indications. 
Opaganib is being evaluated in a global Phase 2/3 study and a U.S. Phase 2 
study for the treatment of severe COVID-19 pneumonia. Opaganib also 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.
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[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 

Under a compassionate use program, patients with severe COVID-19 (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[3]  
[]. Analysis of 
treatment outcomes suggests 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, a 
web-based service by the U.S. National Institute of Health, which provides 
public access to information on publicly and privately supported clinical 

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[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 development programs include: 
(i) RHB-204, with an ongoing Phase 3 study for pulmonary nontuberculous 
mycobacteria (NTM) disease; (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 (upamostat), a Phase 2-stage serine protease 
inhibitor with a planned Phase 2/3 study in symptomatic COVID-19 and targeting 
multiple other cancer and inflammatory gastrointestinal diseases;  and (vi) 
RHB-106, an encapsulated bowel preparation. More information about the Company 
is available at / 

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 include statements regarding the 
timing of the reporting of data from the U.S. Phase 2 trial evaluating 
opaganib, and the timing, if at all, of potential emergency use applications of 
opaganib and reporting of data, from 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 completed or successful; the risk of a delay in receiving data from 
the Phase 2/3 study with opaganib or delay in making 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 other 
COVID-19 patients treated with opaganib will not show any or insufficient 
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; the risk that the ongoing Phase 3 study for pulmonary nontuberculous 
mycobacteria (NTM) disease will be delayed, not be completed, or will not be 
successful, 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 
lack of sufficient financial resources which may result in material adverse 
impact on the Company's research, manufacturing, preclinical studies, clinical 
trials, and other therapeutic candidate development activities including delay 
or termination of preclinical or clinical activities or of any other such 
activities (iii) the Company's ability to advance its therapeutic candidates 
into clinical trials or to successfully complete its preclinical studies or 
clinical trials (iv) 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; (v) the manufacturing, clinical development, 
commercialization, and market acceptance of the Company's therapeutic 
candidates and Talicia®; (vi) the Company's ability to successfully 
commercialize and promote Movantik®, Talicia® and Aemcolo®; (vii) the Company's 
ability to establish and maintain corporate collaborations; (viii) 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; (ix) 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; (x) the implementation of the Company's business model, 
strategic plans for its business and therapeutic candidates; (xi) 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; (xii) parties from whom the Company licenses its 
intellectual property defaulting in their obligations to the Company; (xiii) 
estimates of the Company's expenses, future revenues, capital requirements and 
needs for additional financing; (xiv) the effect of patients suffering adverse 
events using investigative drugs under the Company's Expanded Access Program; 
and (xv) 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

Media contact (U.S.):
Bryan Gibbs
Vice President
Finn Partners
+1 212 529 2236

[1] Opaganib is an investigational new drug, not available for commercial 
[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] 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:
[4] Full prescribing information for Movantik® (naloxegol) is available at:   
[5] Full prescribing information for Talicia® (omeprazole magnesium, 
amoxicillin and rifabutin) is available at:       
[6] Full prescribing information for Aemcolo® (rifamycin) is available at:
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Source:  RedHill Biopharma Ltd.