HONG KONG – Israeli biopharma Redhill Biopharma Ltd. is looking to extend access to its investigational drug, opaganib (Yeliva, ABC-294640), following the drug’s initial success from a compassionate-use study treating six patients in Israel hospitalized with moderate to severe COVID-19 symptoms.
“We are exploring various collaborations in relation to opaganib,” Gilead Raday, Redhill’s chief operating officer, told BioWorld. “We are continuing our efforts to extend access to [the drug] in the U.S. and elsewhere via clinical development programs and compassionate use programs.”
The compassionate use study showed when the opaganib treatment commenced, patients had been treated with mostly hydroxychloroquine and required supplemental oxygenation. After starting treatment with opaganib, patients showed “objective significant measurable clinical improvement within days,” the company said in an April 27 press release. Five of the six patients were subsequently weaned from the supplemental oxygen, with three discharged from the hospital days after the treatment. The remaining patient, whose treatment began later than the others, continues to improve.
Redhill submitted its application to the U.S. FDA on April 17 for a proposed randomized, double-blind, placebo-controlled phase IIa study to evaluate opaganib in up to 60 adult COVID-19 and pneumonia patients in the U.S. Raday said the application is “currently subject to FDA clearance” and the company aims to start the study “promptly” once it is obtained.
“An ensuing phase IIb will be pursued and designed based on analysis of the phase IIa outcomes,” he added. “We have sufficient available drug supply to support phase IIb and phase III studies.”
A total of 131 subjects have been treated with opaganib so far via phase I and phase II studies in oncology indications in the U.S., and in pharmacokinetic studies in healthy volunteers and FDA-approved expanded access requests from physicians for individual oncology patients, according to Redhill.
Opaganib is an orally ingested sphingosine kinase-2 (SK2) selective inhibitor with potential in multiple oncology, inflammatory and gastrointestinal indications. It’s designed to work by blocking the synthesis of sphingosine 1-phosphate, preventing cancer tumor growth, pathological inflammation and potentially viral replication.
“Preclinical data have demonstrated both the anti-inflammatory and antiviral activities of opaganib, with the potential to reduce lung inflammatory disorders, such as pneumonia, and mitigate pulmonary fibrotic damage,” said Raday.
“Several prior preclinical studies support the potential role of SK2 in the replication-transcription complex of positive-strand single-stranded RNA viruses similar to the coronavirus, and its inhibition may potentially inhibit viral replication,” he added. “Preclinical in vivo studies have demonstrated that opaganib decreased fatality rates from influenza-virus infection and ameliorated Pseudomonas aeruginosa-induced lung injury.
“The combined anti-inflammatory activity and antiviral activity against +SS RNA viruses differentiates opaganib and makes it particularly suited to potentially treat the SARS-COVID-2 viral related lung inflammation.”
Opaganib is not the only drug that Redhill is testing against COVID-19. The company also inked an agreement on April 20 with the National Institute of Allergy and Infectious Diseases, part of the U.S. NIH, to test a second investigational drug, RHB-107 (upamostat, WX-671), in COVID-19 patients via nonclinical studies.
More than 300 people across 10 clinical studies have been injected with RHB-107 so far. The company completed phase II studies in cancer patients and a couple of phase I studies in healthy volunteers and cancer patients.
In contrast to opaganib, RHB-107 is a serine protease inhibitor that could inhibit viral attachment and replication, as well as decreasing lung damage from viral pneumonia.
Founded with a primary focus on gastrointestinal diseases, the company’s “robust development pipeline” includes other drugs in various stages of study in the clinic. RHB-104 yielded positive results from a first phase III MAP U.S. study for Crohn's disease in July 2018 following a successful phase IIa proof-of-concept study for multiple sclerosis in Israel in December 2016.
RHB-102 (Bekinda) reported positive results from a phase III study for acute gastroenteritis and gastritis as well as positive results from a phase II study for irritable bowel syndrome with diarrhea. RHB-106, an encapsulated bowel preparation, is being readied for phase II and phase III studies. And RHB-204 is planned to undergo a pivotal phase III study for pulmonary nontuberculous mycobacteria infections.
Redhill is headquartered in Tel Aviv, while its U.S. commercial operations team is based in Raleigh, N.C., and comprises mainly ex-Salix Pharmaceuticals employees.
Redhill is listed on New York’s Nasdaq board. Its stock (NASDAQ:RDHL) rose 12.1% on news of the successful trials. Shares closed April 29 at $7.93.