John Parkinson

RA Therapy Studied for COVID-19 Does Not Meet Endpoint

Tocilizumab does not meet its primary endpoint of improved clinical status in hospitalized adult patients with severe 

 from Roche followed the results of the company’s phase 3 COVACTA trial.

“People around the world are waiting for further effective treatment options for COVID-19 and we are disappointed that COVACTA did not demonstrate a benefit for patients in either clinical status or mortality at week 4,” Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development, said. “We will continue to generate evidence to provide a more complete understanding of Actemra/RoActemra (tocilizumab) in COVID-19 associated pneumonia.”

In addition, the study’s key secondary endpoint, which included the difference in patient mortality at week 4, were not met.

The COVACTA trial is the first global, randomized, double-blind, placebo-controlled phase 3 study to investigate tocilizumab in adult patients hospitalized with severe COVID-19 associated pneumonia, with study locations in the US, Canada, and Europe.

A positive trend witnessed in the trial was the time to hospital discharge in patients treated with tocilizumab. Time to hospital discharge or ‘ready to discharge’ was shorter in patients treated with tocilizumab than in those treated with placebo.

The median time to discharge or ‘ready to discharge’ for tocilizumab was 20 days and for placebo was 28 days (median time [95% CI]: tocilizumab = 20.0 [17.0, 27.0]; placebo = 28.0 [20.0, NE], p=0.0370).

However, the difference cannot be considered statistically significant as the primary endpoint was not met.

Tocilizumab was the first approved anti-IL-6 receptor biologic available in both intravenous and subcutaneous formulations for the treatment of adult patients with moderate-to-severe active 

.

Other results from the CONVACTA trial included, there was no difference between tocilizumab and placebo in the percentage of patients that died by week 4; and the difference in ventilator-free days between tocilizumab and placebo was not statistically significant (median of 22 days for Tocilizumab and 16.5 days with placebo, difference in medians [95% CI] = 5.5 [-2.8, 13.0], p=0.3202).

The COVACTA trial was conducted in collaboration with the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the United States Department of Health and Human Services.

The study did not identify any new safety signals.

Articles

Findings of the trial on tocilizumab fall short.

Tocilizumab Does Not Meet Primary Endpoint in COVID-19 Phase 3 Trial

Pregnant Women with COVID-19 Are at Increased Risk of ICU Admission

,” was originally published online on ContagionLive.

 have more hospitalizations and are at an increased risk of intensive care unit admission and mechanical ventilation.

A team of investigators found 31.5% of pregnant women with COVID-19 were reported to have been hospitalized compared to just 5.8% of nonpregnant women.

 from the US Centers for Disease Control and Prevention (CDC), demonstrated pregnant women were more likely to be admitted to the ICU (aRR = 1.5, 95% confidence interval [CI] = 1.2—1.8) and receive mechanical ventilation (aRR = 1.7, 95% CI = 1.2–2.4).

The study period ran from January 22—June 7, with 326,335 women ages 15-44 testing positive. Of the COVID-19 positive group, 8207 were pregnant.

And Hispanic and black women who are pregnant appear to be at a greater risk to contract COIVD-19, according to the report.

In the COVID-19 pregnant grouping, Hispanics made up 46.2% of the overall group, whites were 23.0%, blacks made up 22.1%, and Asians made up 3.8%.

“These findings suggest that pregnant women who are Hispanic and black might be disproportionately affected by SARS-CoV-2 infection during pregnancy,” the MMWR reported.

In terms of mortality, both groups displayed similar results. In the pregnancy group, there were 16 (0.2%) COVID-19—related deaths, and among nonpregnant women, 208 (0.2%) such deaths.

In terms of limitations, the investigators listed the missing pregnancy status for three-quarters of women of reproductive age with the virus; the need for additional time to see the prevalence of outcomes; data on patients’ pregnancy trimester at the time of infection or whether the hospitalization was related to pregnancy conditions rather than for COVID-19; and routine case surveillance does not capture pregnancy or birth outcomes. The investigators stated that it remained unclear whether COVID-19 during pregnancy is associated with adverse pregnancy outcomes.

In looking to address the aforementioned data gaps, CDC has initiated COVID-19 pregnancy-related surveillance to report pregnancy-related information and outcomes in pregnant women with COVID-19. CDC will be collaborating with local health departments.

“To reduce severe COVID-19-associated illness, pregnant women should be aware of their potential risk for severe COVID-19 illness,” the MMWR stated.

The findings show 31.5% of pregnant women with COVID-19 are hospitalized compared to just 5.8% of nonpregnant women.

COVID-19 Increases ICU Risk Among Pregnant Women

Dexamethasone Reduces Death by 35% in Patients with COVID-19 Respiratory Complications

,” was published online on ContagionLive,

Findings of a new study suggest dexamethasone reduces deaths by one-third in ventilated patients and by one-fifth in patients with 

Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial

,” a UK-based, randomized trial compared the therapy to patients randomized to usual care (control group). The team had 2104 patients receiving dexamethasone 6 mg once daily for 10 days and 4321 patients in the control group.

It was reported that patients on dexamethasone saw a 35% reduction in deaths (rate ratio [RR], 0.65; 95% CI, 0.48-0.88; 

= .0003) versus usual care. Treated patients receiving oxygen reported a 20% reduction in deaths (RR, 0.80; 95% CI, 0.67-0.96; 

Among the patients who received only usual care, the 28-day mortality was highest in those who required ventilation (41%), intermediate in those patients who required oxygen only (25%), and lowest among those who did not require any respiratory intervention (13%).

No benefit was seen in patients who did not require respiratory support (RR, 1.22; 95% CI, 0.86-1.75]; 

Based on these results, 1 death would be prevented by treatment of approximately 8 ventilated patients, or 25 patients requiring oxygen alone.

Co-chief investigator Peter Horby, MD, PhD, professor, Emerging Infectious Diseases in the Nuffield Department of Medicine, University of Oxford, talked about the fact that this is not only the first drug to improve the survival rate in these sicker COVID-19 patients but touted its other benefits as well.

“The survival benefit is clear and large in those patients who are sick enough to require oxygen treatment, so dexamethasone should now become standard of care in these patients,” Horby said. “Dexamethasone is inexpensive, on the shelf, and can be used immediately to save lives worldwide.”

The therapy reduces death by 35% in patients with respiratory complications.

Dexamethasone Demonstrates Strong Results for COVID-19

Phase 3 Study for Baloxavir Shows Efficacy in High-Risk Influenza Patients

,” was originally published on ContagionLive.

Findings of a recent study suggest baloxavir marboxil reduces the time to improvement of 

 symptoms (TTIIS) in patients having at least 1 high-risk factor.

Baloxavir, a selective inhibitor of influenza cap-dependent endonuclease, was approved in the US and Japan in 2018 for the treatment of flu in patients 12 years and older.

Investigators performed a double-blind, placebo-controlled and oseltamivir-controlled trial in patients aged 12 years and older to study the efficacy of baloxavir in outpatients at high risk of developing flu-associated complications. Enrollment included a total of 2184 outpatients.

The study was led by Michael Ison, MD, professor, Division of Infectious Disease and Organ Transplantation, Northwestern University, and an international group of investigators from 551 sites in 17 countries and territories.

“This study supports early therapy for patients at high risk of complications of influenza to speed clinical recovery and reduce complications,” Ison and the team of investigators wrote.

For inclusion, patients had to be diagnosed with an influenza-like illness, had symptoms for less than 48 hours, and had at least 1 risk factor for associated complications.

The primary endpoint was TTIIS in the modified intention-to-treat population. All the patients had to receive at least 1 dose of a study drug and had RT-PCR-confirmed influenza virus. In addition, patient safety was reviewed in all that received at least 1 dose of a study drug.

Overall, 730 participants received baloxavir, 729 received placebo, and 725 received oseltamivir.

TTIIS performance in baloxair (73.2 hours [95% CI, 67.2-85.1]) was better than placebo (102.3 hours [95% CI, 92.7-113.1]), indicating a difference of 29.1 hours (95% CI, 14.6-42.8]; 

< .0001). TTIIS in the oseltamivir-treated patients was 81.0 hours (95% CI, 69.4-91.5), with a difference from the baloxavir group of 7.7 hours (95% CI, −7.9 to 22.7). 

In terms of safety, adverse events were seen in 5 patients for the baloxavir group, 9 patients in the placebo group, and 8 patients in the oseltamivir group. There was 1 case each of hypertension and nausea in the placebo group and 2 cases of transaminase elevation in the oseltamivir group. These cases were considered to be treatment-related.

Overall, the investigators concluded that baloxavir is a viable influenza therapy for clinicians to include in their treatment armamentarium. 

“Single-dose baloxavir has superior efficacy to placebo and similar efficacy to oseltamivir for ameliorating influenza symptoms in high-risk outpatients,” Ison and the team concluded. “The safety of baloxavir was comparable to placebo.”

Early treatment with baloxavir marboxil in high-risk adolescent and adult outpatients with uncomplicated influenza (CAPSTONE-2): a randomized, placebo-controlled, phase 3 trial

The drug reduces the time to improvement of flu symptoms in patients having at least 1 high-risk factor.

Author | John Parkinson

Articles

Tocilizumab Does Not Meet Primary Endpoint in COVID-19 Phase 3 Trial

COVID-19 Increases ICU Risk Among Pregnant Women

Dexamethasone Demonstrates Strong Results for COVID-19

Baloxavir Effective in High-Risk Flu Patients