PCORI Biweekly COVID-19 Scan: Treating COVID-19 Pneumonia and Mild to Moderate COVID-19 (September 30-October 13, 2021)
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.
The work to develop a robust treatment for COVID-19 continues (see Topics to Watch). Recently, Merck and Ridgeback Biotherapeutics submitted an Emergency Use Authorization (EUA) application to the US Food and Drug Administration (FDA) for molnupiravir (for horizon scanning details, see PCORI Biweekly COVID-19 Scan: June 10-23, 2021). However, as some aspects of the pandemic continue, some are asking what comes next.
Predicting pandemics and their impacts has historically been a niche practice. However, many hope to leverage this predictive practice to a greater extent now that society has experienced the consequences of being unprepared. Recent discussions have examined how we might learn from pandemics of the past, acknowledge that present human activity will create spillover events in the future and prepare for that future, possibly with pan-coronavirus vaccines.
A pair of solution scans have compiled the numerous societal and policy options that could give policymakers a head start to prevent animal diseases from crossing to humans and reduce the spread among people to lower the impact or prevent a pandemic when the next virus does spill over.
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.
Lenzilumab to Treat Patients Hospitalized with COVID-19 Pneumonia
At a Glance
- Lenzilumab is a monoclonal antibody that is under investigation to treat patients hospitalized with COVID-19 pneumonia.
- Lenzilumab purportedly binds to and blocks the immune signaling ability of granulocyte-macrophage colony-stimulating factor (GM-CSF), preventing the cytokine storm associated with severe COVID-19 outcomes, including multi-organ failure and death.
- Data released in October 2021 found that lenzilumab improved the likelihood of survival without the need for mechanical ventilation in hospitalized patients who had low oxygen levels. Lenzilumab is currently being compared with placebo in combination with remdesivir in a phase 3 trial with estimated completion in December 2021.
- The FDA rejected the EUA for lenzilumab in September 2021, before the release of new data, but the FDA remains receptive to additional data as it becomes available.
- A preliminary report suggested that before the EUA submission, the manufacturer announced plans to charge about $10 000 per treatment course.
Lenzilumab (Humanigen, Burlingame, California) is a first-in-class monoclonal antibody under investigation to treat patients hospitalized with COVID-19 pneumonia.
Some patients with COVID-19 experience an inflammatory condition leading to pulmonary dysfunction and cardiovascular events thought to contribute to COVID-19–related death. Patients with COVID-19 exhibit elevated levels of various proinflammatory cytokines, including GM-CSF, which is thought to play a key role in disease progression.
Lenzilumab binds to and neutralizes circulating GM-CSF to prevent the cytokine from binding to its receptor and activating downstream inflammatory signaling. This inhibition purportedly reduces the occurrence of cytokine release syndrome, a hyperinflammatory cascade associated with severe COVID-19, and improves outcomes, such as survival without a ventilator, for patients with low oxygen levels.
Preprint results from the phase 3 LIVE-AIR study that enrolled 520 patients hospitalized with severe or critical COVID-19 pneumonia, found that at least 1 dose of lenzilumab treatment significantly improved the likelihood of ventilator-free survival by 54% compared with standard treatment (dexamethasone and other corticosteroids, remdesivir, or both). The treatment was also well-tolerated, with no serious adverse reactions attributed to lenzilumab. Another study investigating lenzilumab or placebo in combination with remdesivir in 400 hospitalized participants is ongoing, with estimated completion expected in December 2021. A preliminary report suggested that before the EUA submission, the manufacturer announced plans to charge about $10 000 per course.
Although vaccine uptake is high, many individuals are still at risk of contracting COVID-19 due to breakthroughs from viral variants. Lenzilumab might be able to improve health outcomes for those hospitalized with COVID-19 pneumonia by preventing the hyperinflammation that can be critical and requires respiratory support.
Early feedback from ECRI internal stakeholders suggests that, if effective, lenzilumab might improve patient health outcomes by reducing the onset of strong and uncontrolled immune responses and the need for treatment with ventilation. Severe COVID-19 is associated with worsening outcomes but lenzilumab might be able to limit disease progression early in patients requiring hospitalization before it advances to severe health complications or death. Treatment with lenzilumab might also decrease the time spent in the hospital, thereby reducing costs and allowing resources to be used for other hospitalized patients.
Stakeholders expressed concerns that disparities might be increased if the treatment is only available to large health systems and not accessible to those living in rural areas. Although an effective treatment might positively impact treatment outcomes, increased availability of effective treatment options might encourage some patients to remain unvaccinated and solely depend on new treatments if infected.
- Categories: Public health, systems, and management
- Areas of potential impact: Patient outcomes, population health outcomes, patient management, health care disparities, health care delivery and process
PUL-042 to Treat Mild to Moderate COVID-19
At a Glance
- PUL-042 is an inhaled nebulized drug that comprises 2 synthetic toll-like receptor (TLR) agonists, TLR 2/6 and TLR 9, and is being investigated to treat adults with mild to moderate COVID-19.
- Treatment with PUL-042 purportedly stimulates the body’s natural first-line immune responses (ie, innate immunity) to rapidly eliminate the SARS-CoV-2 virus and reduce the duration of respiratory symptoms.
- Topline data reported from a phase 2 randomized controlled clinical trial in 101 adults with mild to moderate COVID-19 found that after the 6-day treatment period, the median time to the improvement of respiratory symptoms (eg, cough, shortness of breath) was 6 days for PUL-042, compared with 9 days for patients given placebo.
- Pulmotect plans to submit an EUA to the FDA for PUL-042 in 2021.
The innate immune system is the first line of defense against COVID-19 infection. TLRs play a central role in triggering the body’s immune response to viruses. PUL-042 (Pulmotect, Inc., Houston, Texas) is a nebulized inhaled drug that comprises 2 synthetic TLR agonists, acting on TLR 2/6 and TLR 9, and is being investigated to treat adults with mild to moderate COVID-19 by purportedly stimulating the body’s innate immune system to eliminate the SARS-CoV-2 virus.
PUL-042 is thought to work rapidly, within hours, to activate natural first-line immune responses in surface lung cells, preventing viral entry and replication. This agent has shown benefit in preclinical studies against other coronaviruses, including Middle East respiratory syndrome (CoV MERS-CoV) and severe acute respiratory syndrome [CoV (SARS)]. Treatment with PUL-042 might protect the lungs from damage caused by viral entry, reducing disease severity and the duration of respiratory symptoms. In pre-clinical studies, PUL-042 demonstrated protection against a wide range of respiratory infections, including other coronaviruses.
Topline data from a phase 2 randomized controlled clinical trial in 101 adults with mild to moderate COVID-19, but not requiring high-flow oxygen or mechanical ventilation, found that after the 6-day treatment period, the median time to the improvement of respiratory symptoms (eg, cough, shortness of breath) was 6 days for PUL-042, compared with 9 days for patients given placebo. Development of PUL-042 is funded by the US Department of Defense and is also being investigated in a phase 2 randomized controlled clinical trial to prevent infection and progression to COVID-19 in adults exposed to SARS-CoV-2. Pulmotect plans to submit an EUA to the FDA for PUL-042 in 2021. The authors were unable to find information regarding the potential cost of PUL-042.
PUL-042 is an investigational nebulized inhaled therapy to treat patients with mild to moderate COVID-19. If authorized by the FDA, it could be the first inhaled therapy administered at home to reduce the duration of respiratory symptoms associated with COVID-19 infection.
Early feedback from ECRI internal stakeholders suggests that, if safe and effective, PUL-042 might prevent disease progression, speed recovery, and reduce transmission, leading to improved patient health outcomes.
The drug might decrease demands on the health care system by limiting disease duration and severity, potentially alleviating staffing and bed shortages. Stimulating the body’s innate immune response might reduce the risk of cytokine release syndrome, preventing the damaging hyperinflammatory response associated with severe COVID-19. Additionally, PUL-042’s broad efficacy against a range of viruses might help mitigate the threat of infections due to current or emergent variants.
PUL-042 might lower health care costs associated with hospitalization, mechanical ventilation, and COVID-19–related health complications. Diffusion is more likely if PUL-042 costs less than monoclonal antibodies. Health disparities might increase if access to the treatment is limited by insurance coverage, geographic availability, or patient eligibility.
- Category: Treatment
- Areas of potential impact: Patient outcomes, patient management, health care disparities, health care costs
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.
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: October 26, 2021
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