RedHill Biopharma Announces Positive Assessment of DSMB Futility for Phase 2/3 Study of Opaganib for COVID-19
Wednesday, February 03, 2021
RedHill Biopharma Ltd., a specialty biopharmaceutical company, announced that the independent Data and Safety Monitoring Committee (DSMB) appointed for the global phase 2/3 study of opaganib [1] in patients with severe COVID-19 unanimously recommended the continuation of the study, after a pre-scheduled evaluation of futility of the unblinded data for the first 135 patients treated in the study, as well as the safety information of the first 175 patients.
"Opaganib is a novel orally administered sphingosine kinase-2 (SK2) inhibitor with proven antiviral, anti-inflammatory and antithrombotic activity. The positive and unanimous recommendation of the DSMB is an important milestone in the progress of our development program for the COVID-19 disease. Along with the positive results of the phase 2 study , this unanimous recommendation from DSMB to continue the global phase 2/3 study suggests that we are heading in the right direction from a safety and efficacy perspective, " commented Mark L. Levitt , MD, Ph.D., RedHill Medical Director. "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 therapies is clear. The mechanism of action for Opaganib targets the SK2 component of the human host cell, which is involved in both viral replication within the cell and subsequent inflammatory / immune responses. This means that opaganib is expected to maintain its activity regardless of worrisome mutations in the spike protein SARS-CoV-2 These mutations underscore the potential for SARS-CoV-2 to develop resistance to direct antiviral mAbs and to potentially affect the effectiveness of the vaccine.
This positive futility rating from the DSMB, suggesting that the global phase 2/3 study is progressing as expected, adds to the positive first-line safety and efficacy data from the phase 2 study in the United States, in that opaganib demonstrated improvement in the reduction of oxygen requirement at the end of treatment, on day 14, in the key primary and secondary efficacy outcomes, which correlates with clinical improvement according to the ordinal scale of the World Health Organization. Health (WHO). The phase 2 data also showed no substantial differences in safety between the opaganib and placebo treatment arms, adding to the growing safety database for opaganib. A full analysis of the phase 2 data is expected in the coming weeks,
In line with rapidly evolving clinical practice and guidelines for the treatment of hospitalized patients with COVID-19, which aim to minimize intubation and mechanical ventilation of patients, the primary endpoint of the global phase 2/3 study now is the proportion of patients who by day 14 are able to breathe on their own (no longer require supplemental oxygen), which was previously a key secondary variable. Intubation and mechanical ventilation remain a secondary endpoint. Consequently, a blind adjustment of the study is planned for approximately 460 patients. There are currently approximately 30 study sites in 7 countries, and more sites and countries will be added in the coming days and weeks.
About Opaganib (Yeliva ® , ABC294640)
Opaganib, a new proprietary and first-in-class chemical entity, is a novel orally administered selective sphingosine kinase-2 (SK2) inhibitor with demonstrated dual antiviral and inflammatory activity targeting the cellular component in the host which is responsible for the replication of the virus, and can reduce the probability of developing virus resistance. Opaganib has also shown anti-cancer activity and has the potential to target multiple oncological, viral, inflammatory, and gastrointestinal indications.
Opaganib received orphan drug designation from the United States Food and Drug Administration (FDA) for the treatment of cholangiocarcinoma and is being evaluated in a phase 2a study for patients with advanced cholangiocarcinoma and in a phase 2 study for prostate cancer patients. Opaganib is also being evaluated as a treatment for COVID-19 pneumonia in a global phase 2/3 study and has shown positive signs of safety and efficacy in preliminary first-line data from a phase 2 study in the United States. .
Preclinical data have demonstrated the anti-inflammatory, antiviral, and antithrombotic activities of opaganib, with the potential to alleviate inflammatory lung disorders, such as pneumonia, and to mitigate fibrotic lung damage. Opaganib demonstrated potent antiviral activity against SARS-CoV-2, the virus that causes COVID-19, by completely inhibiting viral replication in an in vitro model of human bronchopulmonary tissue. Opaganib also demonstrated a reduction in blood clot length, weight, and total thrombus score in a preclinical model of acquired respiratory distress syndrome. Additionally, in vivo preclinical studies [2] have shown that opaganib decreases the case fatality rate from influenza viral infection and improves lung damage induced by Pseudomonas aeruginosa by reducing the levels of IL-6 and TNF-alpha in bronchoalveolar irrigation fluids.
Opaganib was originally developed by Apogee Biotechnology Corp. in the United States and completed multiple successful preclinical studies in oncology, inflammatory, gastrointestinal, and radioprotective models, as well as a phase 1 clinical study in cancer patients with advanced solid tumors and one study additional phase 1 in patients with multiple myeloma.
The development of opaganib has been supported by grants and contracts from United States federal and state government agencies, awarded to Apogee Biotechnology Corp., which include the NCI, BARDA, the United States Department of Defense and the Office of Development of Orphan Products from the FDA.
Ongoing studies with opaganib are registered at www.ClinicalTrials.gov , a web service of the US National Institutes of Health , which provides public access to information on publicly and privately funded clinical trials.
About RedHill Biopharma
RedHill Biopharma Ltd. is a specialty biopharmaceutical company with a primary focus on gastrointestinal and infectious diseases. RedHill promotes gastrointestinal medications, 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 traveler's diarrhea in adults [5] . RedHill's key late-stage clinical research programs under development include the following: (i) RHB-204, with an ongoing phase 3 study for nontuberculous mycobacterial (NTM) lung 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 2/3 pass study for symptomatic COVID-19 and also targeting multiple inflammatory gastrointestinal diseases and cancer (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 preparation for the intestine. In www.redhillbio.com more information is available about the company / https://twitter.com/RedHillBio.
NOTE: This press release, presented for practical purposes, is a translated version of the official press release published by the company in English. To read the full press release in English, including the disclaimer of forward-looking statements, please visit: https://ir.redhillbio.com/press-releases
Company Contact:
Adi frish
Executive Director of Corporate & Business Development
RedHill Biopharma
+ 972-54-6543-112
adi@redhillbio.com
Press Contact (USA):
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 kinase provides protection against influenza A virus in infected mice. Antiviral Res. 2018 Oct; 158: 171-177. Ebenezer DL et al. Pseudomonas aeruginosa stimulates the nuclear generation of sphingosine-1-phosphate and the epigenetic regulation of inflammatory damage to the lung. 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 .
