PCORI Biweekly COVID-19 Scan: Two Treatments for Patients with COVID-19 and Pneumonia (November 24-December 7, 2022)
The Briefing provides an at-a-glance view of some important developments in the information universe surrounding COVID-19. The views presented here are solely those of ECRI Horizon Scanning and have not been vetted by other stakeholders.
As winter approaches, the numbers of COVID-19 cases, positive COVID-19 tests, and COVID-19–related hospitalizations appear to be increasing. Because many Americans are now testing at home, the National Institutes of Health (NIH) have launched the MakeMyTestCount website, which enables people with internet access to report their at-home test results.
Paxlovid has been shown to decrease hospitalization rates for adults. A recent Centers for Disease Control and Prevention (CDC) investigation of electronic health records (EHR) of 699,848 adults aged 18 years and older who were eligible for Paxlovid during April–August 2022, found that only 28.4 percent of eligible patients received a Paxlovid prescription within 5 days of COVID-19 diagnosis. Those who took Paxlovid within 5 days of diagnosis had a 51 percent lower rate of hospitalization than those who did not. Hesitency around taking the drug seems to stem from concerns regarding treatment side effects and viral rebound.
Preventing hospitalizations is especially important while flu cases and hospitalizations are rising, and emerging SARS-CoV-2 variants appear to be outpacing treatments for severe COVID-19. Most recently, the Emergency Use Authorization (EUA) for the antibody bebtelovimab was revoked because the drug does not neutralize Omicron subvariants BQ.1 and BQ1.1, which are currently dominant in the US. See Topics to Watch for 2 emerging treatments for hospitalized patients.
ECRI Horizon Scanning has selected the topics below as those with potential for impact relative to COVID-19 in the United States within the next 12 months. All views presented are preliminary and based on readily available information at the time of writing.
Because these topics are rapidly developing, we cannot guarantee the accuracy of this information after the date listed on this publication. In addition, all views expressed in the commentary section are solely those of ECRI Horizon Scanning and have not been vetted by other stakeholders. Topics are listed in alphabetical order.
Subcutaneous Anakinra (Kineret) to Treat Hospitalized COVID-19 Patients with Pneumonia at Risk of Progressing to Severe Respiratory Failure
At a Glance
- The clinical course of SARS-CoV-2 infection can be unpredictable. Detecting early biomarkers of severe disease might aid in management and improve patient health outcomes. Urokinase plasminogen activator receptor (uPAR) is a protein expressed by activated immune cells. Early detection of elevated levels of soluble urokinase plasminogen activator receptor (suPAR) in blood might effectively predict progression to severe COVID-19.
- Anakinra (Kineret) is an immunosuppressive drug that blocks the activity of cytokines IL-1α and β and is being developed as a treatment for patients hospitalized with COVID-19 pneumonia who are at risk of progressing to severe respiratory failure.
- A recent phase 3 study reported that early, suPAR-guided anakinra plus standard-of-care treatment reduced 28-day mortality, progression to severe respiratory failure by 3-fold, and the average time until intensive care unit discharge by 4 days.
- Based on these results, in November 2022, the FDA granted anakinra Emergency Use Authorization (EUA) for this indication.
- A 10-day course of anakinra, given as a 100-mg once-daily injection under the skin, might cost about $1,810.
Anakinra (Kineret) (Amgen, Thousand Oaks, California) is an anti-inflammatory drug designed to neutralize the biological activity of cytokines IL-1α and β, which are thought to play a role in COVID-19–induced hyperinflammation and disease progression. It is currently being developed to treat patients hospitalized with COVID-19 pneumonia who are at risk of progressing to severe respiratory failure.
Severe COVID-19 is characterized by excessive cytokine production and inflammation, which might lead to lung damage, respiratory difficulty, and even death. Disease progression is variable among patients and remains difficult to predict. Evidence suggests that early elevations in serum levels of soluble urokinase plasminogen activator receptor (suPAR) might give health care providers a valuable tool to predict which patients are at increased risk of progression to respiratory failure. Earlier intervention using anakinra to dampen the IL-1 pathway might improve patient outcomes.
A recent phase 3 clinical trial, enrolling patients (n = 594) hospitalized with COVID-19 pneumonia at risk for respiratory failure, found that suPAR-guided (levels > 6 ng/ml) treatment with anakinra plus standard-of-care (SOC) reduced 28-day mortality (hazard ratio = 0.45, P = 0.045), decreased progression to severe respiratory failure by 3-fold, and reduced the average time until intensive care unit discharge by 4 days compared with placebo. These effects were reported to be durable and sustained. Based on these data, in November 2022, the FDA granted anakinra EUA to treat hospitalized adults with pneumonia that required supplemental (low- or high-flow) oxygen who are at risk of progressing to severe respiratory failure.
A 10-day course of anakinra, given as a 100-mg once-daily injection under the skin, might cost about $1,810. In Europe, anakinra treatment reduced the median cost of hospitalization by 46 percent relative to SOC.
Reliable biomarkers of progression to severe COVID-19, and effective treatments to respond to these indications, are needed to improve patient outcomes. Evidence suggests suPAR-guided anakinra treatment reduces risk of severe respiratory failure and mortality, as well as time in an intensive care unit (ICU).
Feedback from ECRI stakeholders suggested that physicians might be more inclined to prescribe anakinra because it is FDA-approved for several other indications. Anakinra might improve patient outcomes and reduce hospitalization times, thereby decreasing hospital costs, freeing up resources, and enhancing the facility’s ability to effectively manage patients. However, COVID-19 booster vaccination uptake rates are lower than with previous doses, and this might result in higher demand for acute care treatments.
Although anakinra is reported to reduce progression to severe respiratory failure, hospital resources are still being utilized until discharge when patients require pulmonary rehabilitation. However, as supported by data from European hospitals, overall cost might be decreased compared to current standard of care. Disparities in access might arise for those uninsured.
- Category: Treatment
- Areas of potential impact: Patient management, patient outcomes, health care costs, health care disparities
Vilobelimab (IFX-1) to Treat Severe COVID-19 Pneumonia
At a Glance
- Severe COVID-19 pneumonia is associated with poor overall outcomes and high mortality rate (40%) in hospitalized, mechanically ventilated patients. A significant unmet need remains for effective treatments.
- The complement system enhances the immune system’s ability to fight bacterial and viral infection. In some diseases, possibly including COVID-19, dysregulation of the complement system can instead contribute to disease pathology.
- Vilobelimab is a monoclonal antibody which inhibits complement factor C5a. It is designed to dampen the runaway, damaging immune response, but preserve the ability to respond to and eliminate pathogens.
- Results published in September 2022 indicate that vilobelimab was well tolerated and decreased overall mortality by 10% in patients hospitalized with COVID-19–related severe pneumonia and who were mechanically ventilated. The developer has applied for EUA based on these data.
Vilobelimab (IFX-1) is an investigational treatment for COVID-19–related severe pneumonia in patients who are hospitalized and mechanically ventilated. It is being developed by InflaRx NV (Jena, Germany).
COVID-19 pneumonia is a condition where the lungs become inflamed and filled with fluid as the immune system fights SARS-CoV-2 infection, leading to respiratory distress (difficulty breathing). The overall severity of COVID-19 is heavily influenced by the individual’s immune response; patients with mild COVID-19 and patients who recover from severe COVID-19 exhibit normal immune responses to eliminate the virus, whereas immune hyperactivation in critical patients instead contributes to pathology. Evidence suggests that the complement system, a part of the innate immune system that is vital for the body’s first-line response in clearing pathogens, is hyperactive in patients with severe COVID-19 and might be a therapeutic target.
Complement factor C5a recruits inflammatory cells (eg, neutrophils, T-cells) and activates inflammatory cytokines (eg, interleukin-6, tumor necrosis factor alpha). Vilobelimab is a monoclonal antibody designed to inhibit C5a activity, and is therefore intended to reduce systemic inflammation, and reduce the risk of progression to severe COVID-19 pneumonia. Results published from the phase 2/3 PANAMO trial found that vilobelimab was well tolerated and improved survival of patients on invasive mechanical ventilation. In September 2022,the developers submitted an EUA for vilobelimab to treat patients critically ill with COVID-19.
We were unable to find information regarding the potential cost of a course of vilobelimab treatment.
Severe COVID-19 pneumonia remains associated with high mortality, especially in resource-constrained settings, and new treatments are needed to improve patient health outcomes.
Feedback from ECRI stakeholders suggested that vilobelimab, when added to SOC treatment, might increase survival rates in a patient population with limited treatment options (eg, dexamethasone). As the pandemic persists, new SARS-CoV-2 variants arise making viral spike protein–targeted treatments ineffective, so additional options are needed. Selective suppression of complement factor C5a might differentiate this treatment from comparators by preserving other critical immune functions.
With vilobelimab’s current cost unknown, disparities regarding its affordability, even for the insured, might arise. Additional studies on vilobelimab might help determine the treatment’s disruptive potential.
- Category: Treatment
- Areas of potential impact: Patient health outcomes, costs, population health outcomes, patient management
Horizon scanning is a systematic process that serves as an early warning system to inform decision makers about possible future opportunities and threats. Health care horizon scanning identifies technologies, innovations, and trends with potential to cause future shifts or disruptions—positive or negative—in areas such as access to care, care delivery processes, care setting, costs of care, current treatment models or paradigms, health disparities, health care infrastructure, public health, and patient health outcomes.
The PCORI Health Care Horizon Scanning System (HCHSS) conducts horizon scanning to better inform its patient-centered outcomes research investments. Initially, PCORI defined the HCHSS project scope to focus on interventions with high potential for disruption in the United States in 5 priority areas: Alzheimer’s disease and other dementias, cancer, cardiovascular diseases, mental and behavioral health conditions, and rare diseases. In addition, the system captures high-level disruptive trends across all clinical areas, which may lead PCORI to expand the project scope to include other priority areas in the future.
In early 2020, the COVID-19 pandemic created a fast-moving, widespread public health crisis. In May 2020, PCORI expanded its HCHSS to elucidate the landscape of potentially impactful applications for COVID-19. The HCHSS COVID-19 supplement scans for, identifies, monitors, and reports on emerging and available COVID-19-related treatments, diagnostics, preventive measures, management strategies, and systems changes with potential for high impact to patient outcomes—for individuals and populations—in the United States in the next 12 months.
The HCHSS COVID-19 supplement produces 3 main outputs:
- Biweekly COVID-19 Scans (eg, this document) provide ECRI Horizon Scanning with a vehicle to inform PCORI and the public in a timely manner of important topics of interest identified during ongoing scanning and topic identification or through the ECRI stakeholder survey process.
- Status Reports (quarterly) briefly list and describe all COVID-19-related topics identified, monitored, and recently archived.
- High Impact Reports (every 4 months) highlight those topics that ECRI internal stakeholders (eg, physicians, nurses, allied health professionals, public health professionals, first responders, health systems experts, clinical engineers, researchers, business and finance professionals, and information technology professionals) have identified as having potential for high impact relative to COVID-19 in the United States.
In May 2021, the COVID-19 supplement was modified and merged with the HCHSS. The Biweekly COVID-19 Scans continue, while the Status Reports and High Impact Reports were folded into the PCORI Horizon Scanning Database and High Potential Disruption Reports.
Commentary in this COVID-19 Scan reflects preliminary views of ECRI Horizon Scanning and internal ECRI stakeholders.
The information contained in this document has not been vetted by other stakeholders.
We welcome your comments on this Scan. Send them by email to [email protected].
Posted: December 19, 2022
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