The oral microtubule disruptor sabizabulin has been found in an RCT to significantly reduce mortality in high patients with severe COVID-19
Use of the oral microtubule disruptor, sabizabulin, has been found to significantly reduce the mortality risk among patients hospitalised with COVID-19 and at a high risk of acute respiratory distress syndrome according to the results of a randomised, placebo-controlled trial by an international group of researchers.
Within cells the cytoskeleton represents a complex and dynamic network of interacting protein filaments with multiple roles and is composed of three major types of protein filaments: actin filaments, intermediate filaments, and microtubules. During an infection, once a virus gains entry to a cell, it requires cytoplasmic transport to reach specific sub-cellular sites for replication and the cytoskeleton microtubules represent a heavily exploited network during viral infection. Sabizabulin is a novel agent that disrupts the microtubule and hence interferes with viral replication. Furthermore, in vivo data suggests that sabizabulin can suppress some of the key cytokines involved in the development of acute respiratory distress syndrome.
To test the value of the drug in vivo, researchers undertook the VERU-111 trial and which was designed to test the efficacy of VERU-111 (sabizabulin) in the treatment of COVID-19 infection. The study recruited adults with a laboratory confirmed COVID-19 infection, a World Health Organisation (WHO) 9-point ordinal scale for clinical improvement score of at least 4 (i.e., oxygen mask or nasal prongs), an elevated body mass index (BMI) and a co-morbidity known to place the individual at a high risk of more severe disease (e.g., asthma, diabetes, hypertension etc). Participants were randomised 2:1 to receive sabizabulin 9 mg daily or matching placebo for 21 days or until hospital discharge. The researchers set the primary efficacy endpoint as the level of 60-day all-cause mortality whereas secondary endpoints included differences in intensive care unit (ICU) days, the number of days on mechanical ventilation and time spent in hospital.
Sabizabulin and COVID-19 mortality
A total of 150 patients with a median age of 64 years (68% male) were randomised to sabizabulin (98) or placebo. For the entire study cohort, the median BMI was 31.7 and the median WHO ordinal scale score was 5. In addition, diabetes and hypertension were present in 37.3% and 60% of patients respectively. Overall, 55.3% of participants had not been vaccinated against COVID-19.
The primary outcome occurred in 20.2% of those taking sabizabulin and 45.1% of placebo patients and this difference was statistically significant (odds ratio, OR = 3.23, 95% CI 1.45 – 7.22, p = 0.0042). In fact, researchers observed that the benefits of treatment with sabizabulin were apparent after only 3 days and there were significant differences in mortality seen by day 15.
For the secondary endpoints and based on a relative risk reduction, treatment with sabizabulin led to a 43% lower number of ICU days (p = 0.0013), a 49% decrease in the number of days requiring mechanical ventilation (p = 0.0013) and a 26% decrease in the number of days spent in hospital (p = 0.00277).
Adverse events leading to discontinuation of treatment occurred in 4.7% and 5.9% of patients receiving sabizabulin and placebo respectively.
The authors concluded that sabizabulin was both effective at reducing mortality in patients with COVID-19 and had an acceptable safety profile.
Barnette KG et al. Oral Sabizabulin for High-Risk, Hospitalized Adults with Covid-19: Interim Analysis New Eng J Med 2022