New cancer drug halves deaths in hospitalized COVID-19 patients
The experimental cancer drug sabizabulin reduced all-cause deaths by 55.2% relative to placebo in high-risk hospitalized COVID-19 patients by 60 days and was linked to fewer side effects, according to interim results from a randomized, controlled phase 3 study published yesterday in NEJM Records†
Scientists at sabizabulin manufacturer Veru, Inc. led the multicenter trial of the oral drug, which demonstrated both antiviral and anti-inflammatory properties in preclinical models. The drug binds to the microtubules critical for SARS-CoV-2 cell entry and replication and for the excessive inflammatory response that leads to acute respiratory distress syndrome (ARDS) and death.
A total of 204 adults with moderate to severe COVID-19 at high risk of poor outcomes were randomly assigned to receive 9 milligrams of sabizabulin or a placebo daily for up to 21 days. The study was stopped early due to the drug’s demonstrated efficacy, resulting in the inclusion of 150 patients (98 assigned to sabizabulin and 52 to placebo) in the analysis, of whom 145 completed the study and had a known status after 60 days.
Patients were enrolled at 27 sites in five countries – the United States, Brazil, Bulgaria, Argentina and Mexico – from May 18, 2021 to January 31, 2022.
Sabizabulin resulted in an absolute reduction of 24.9 percentage points and a relative reduction of 55.2% in the number of deaths relative to placebo (odds ratio, 3.23; 95% confidence interval, 1.45 to 7.22). Nineteen of 94 sabizabulin recipients (20.2%) died, compared with 23 of 51 placebo recipients (45.1%).
Relative to placebo recipients, the sabizabulin group also saw a 43% relative reduction in the mean number of days in an intensive care unit (-13.4 days), a relative reduction of 49% in the number of days on mechanical ventilation ( -14.1) and a relative reduction of 26% in hospital days (-8.4). Adverse reactions were less frequent in sabizabulin recipients (61.5%) than in the placebo group (78.3%).
“These data demonstrate that sabizabulin treatment significantly reduced mortality with an acceptable side effect and safety profile in hospitalized patients with moderate to severe COVID-19 at high risk for ARDS,” the researchers concluded.
6th of July NEJM Records study
Hospitalized immunocompromised people at higher risk of severe COVID
According to an analysis led by researchers at the Centers for Disease Control and Prevention (CDC), immunocompromised adults hospitalized for COVID-19 are at greater risk of intensive care (ICU) admission and death, regardless of vaccination status.
They based their findings on data from 10 of the states participating in the COVID-19-Associated Hospitalization Surveillance Network collected from March 1, 2020 to February 28, 2022. The team published its findings today in Morbidity and Mortality Weekly Report (MMWR)†
Of the 23,345 adults hospitalized for COVID-19, 12.2% were immunocompromised. By comparison, about 2.7% of the adult U.S. population is made up of people with immunocompromised levels. Of the unvaccinated patients, those with a weakened immune system had a higher chance of being admitted to the ICU (adjusted odds ratio [aOR] = 1.26; 95% CI = 1.08–1.49) and death (aOR = 1.34; 95% CI = 1.05–1.70). When the researchers looked at vaccinated patients, those who were immunocompromised had a greater chance of intensive care admission (aOR = 1.40; 95% CI = 1.01-1.92) and death (aOR = 1.87; 95% CI = 1.28-2.75).
By focusing only on the March 2021 to February 2022 period in people who were not immunocompromised, vaccinated people had a lower risk of death than unvaccinated people. However, in those who were immunocompromised, the odds of death did not vary by vaccination status.
“The generally consistent association of individual immunocompromising conditions with an increased risk of death suggests that immunocompromise itself was likely associated with serious outcomes,” the group wrote, adding that in-group COVID-19 vaccination is highly protective against hospitalization. but once included, vaccination status was not associated with IC admission or death.
The increased likelihood of serious outcomes in immunocompromised people hospitalized with COVID-19 underscores the need for multi-layered prevention strategies for this group, such as ensuring close contacts are up-to-date with vaccinations, and encouraging immunocompromised people to using pre-exposure prophylaxis, such as Evusheld, and early testing and treatment.
8 July MMWR report