Veru Announces Preclinical Results from Expanded Sabizabulin Program into Influenza-Induced Severe Acute Respiratory Distress Syndrome and Provides Update on COVID-19 Program :: Veru Inc. (VERU) (verupharma.com)
In the final report, sabizabulin significantly reduced key cytokines involved in Acute Respiratory Distress Syndrome (ARDS) in H1N1 influenza pulmonary inflammation murine ARDS model
Positive Phase 3 COVID-19 clinical study and preclinical influenza study further support the potential use of sabizabulin as a broad antiviral and anti-inflammatory agent for viral-induced ARDS
Expedited meeting granted by U.S. FDA in April 2023 for Phase 3 confirmatory study in hospitalized COVID-19 patients at high risk for ARDSVeru plans Phase 3 clinical study in hospitalized influenza patients at high risk for ARDS
MIAMI, FL, April 04, 2023 (GLOBE NEWSWIRE) -- Veru Inc. (NASDAQ: VERU), Veru Inc., a biopharmaceutical company focused on developing novel medicines for COVID-19 and other viral ARDS-related diseases and for oncology, today announced results from a preclinical study of sabizabulin demonstrating robust anti-inflammatory activity with improved outcomes in an Influenza-Induced Pulmonary Inflammation Mouse Acute Respiratory Distress Syndrome (ARDS) Model.
Preclinical study background:
An animal study was conducted by a team of researchers at Labcorp Early Development Laboratories, Ltd, United Kingdom. The purpose of the study was to evaluate the efficacy of sabizabulin in the influenza H1N1 pulmonary inflammation mouse ARDS model. Two hours before starting treatment, mice were administered H1N1 or saline via the intranasal route to induce a viral infection and inflammatory response in the lung followed by daily treatments with saline, sabizabulin, dexamethasone (anti-inflammatory control), or oseltamivir (direct antiviral control).
Clinical signs and longitudinal lung function (Penh) were measured, bronchioalveolar lavage (BAL), which is washings from lungs, was collected to determine both amounts of inflammatory cells and levels of cytokines, and histopathologic examination of lungs was performed to evaluate inflammation.
Preclinical study results highlights:
Sabizabulin treatment resulted in a statistically significant decrease in the total number of inflammatory cells (-53%) (p<0.01) in BAL fluid, including statistically significant reductions in both the innate and adaptive immune cells. In addition, sabizabulin treatment showed a statistically significant reduction in key cytokines and chemokines in BAL fluid that are part of the cytokine storm responsible for the acute lung injury: Keratinocyte-derived chemokine (KC) (-38%;p<0.01), Interleukin-6 (IL-6) (-74%;p<0.001), TNF-a (-36%;p<0.05), Interferon-? ( INF-?) (-84%;p<0.001), and CXCL-10 (-60%;p<0.001). In contrast, dexamethasone treatment did not demonstrate a statistically significant reduction in the total number of inflammatory cells in the BAL fluid. Dexamethasone also had a different effect from sabizabulin on cytokine production in the BAL fluid. Dexamethasone treatment resulted in statistically significant reductions for IL-6 (-52 %;p<0.01) and INF-? (-81 %;p<0.001), but no statistically significant changes for KC (+20%), TNF-a (-13%), and CXCL- 10 (-8%).
Clinically, sabizabulin treatment resulted in a reduction in the severity of lung inflammation (by histopathology) and a dose-dependent improvement of lung function (lower Penh vs untreated H1N1 infection). Oral administration of 2 mg/kg sabizabulin resulted in the reduction of the clinical signs and body weight loss associated with H1N1 infection. From Day 11, four out of seven animals displayed no clinical signs associated with the induction of H1N1 infection. Whereas, oral administration of 1 mg/kg dexamethasone did not result in reduction of the clinical signs or body weight loss associated with H1N1 infection.
The Company expects to submit the full data set for presentation in future scientific meetings and peer-reviewed publications.
Sabizabulin’s anti-inflammatory effects were previously reported in a preclinical septic shock mouse model with suppression of key cytokines responsible for severe acute respiratory distress syndrome (ARDS). This mouse model predicted the clinical benefit of sabizabulin demonstrated in a positive randomized, multicenter placebo-controlled Phase 3 clinical trial in hospitalized moderate to severe COVID-19 patients who were at high risk for ARDS and death. Sabizabulin treatment plus standard of care resulted in a 51.6% relative reduction in deaths compared to placebo plus standard of care (odds ratio, 2.77; 95% CI confidence interval, 1.37 to 5.60; p=0.0046).
These data suggest that sabizabulin has the potential to be an effective treatment for hospitalized influenza patients at high risk for ARDS and death. Pathogenesis and mortality rates for patients with hospitalized influenza ARDS are similar to COVID-19-associated ARDS, representing a high unmet need with very limited treatment options. According to CDC, the influenza burden estimates in the United States were up to 630,000 hospitalizations and up to 55,000 deaths in the past 6 months. Accordingly, Veru is planning a double-blind randomized placebo-controlled Phase 3 clinical trial evaluating sabizabulin in hospitalized adult influenza patients at high risk for ARDS.
“Viral-induced acute respiratory distress syndrome is a leading cause of death in patients with COVID-19 and influenza and remains an unmet medical need worldwide,” said Mitchell Steiner, M.D., Chairman, President and Chief Executive Officer of Veru. “Sabizabulin, as a host targeted antiviral and broad spectrum anti-inflammatory agent, has the potential to address the two most common causes of viral-induced ARDS: COVID-19 and influenza. Based on the preclinical data highlighted today, we plan to initiate a Phase 3 study of sabizabulin in influenza patients at high risk for ARDS, as well as expand the sabizabulin program into other serious virus infections that result in ARDS and potentially death. Furthermore, we look forward to providing an update on the upcoming FDA meeting we will be having this month to finalize the clinical trial design for the Phase 3 confirmatory COVID-19 study and to confirm the requirements for an EUA submission and new drug application.” |
