PCORI Biweekly COVID-19 Scan: Treating Post-COVID Conditions and Patients in Critically Ill Conditions (September 29-October 12, 2022)

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.

Description

Apabetalone, formerly known as RVX-208, is an oral small-molecule drug being investigated as a treatment for post-COVID conditions (PCC), which encompasses a broad range of new or worsening symptoms lasting months after SARS-COV-2 infection. This commonly includes fatigue, headaches, difficulty concentrating, joint and muscle pain, and breathing problems. It is intended to work by blocking bromodomain and extra-terminal (BET) proteins, which play an important role in the transcriptional regulation of inflammation. BET proteins are involved in the initial, innate immune response to infection and dysregulated BET proteins might play a role in systemic inflammation and symptoms of chronic diseases.

Apabetalone was being studied in a phase 2/3 trial as a potential treatment for severe COVID-19 after 2 in vitro studies suggested that apabetalone might inhibit SARS-CoV-2 infection by decreasing the expression of cell surface receptors that the virus uses to enter and infect cells and prevent cardiac dysfunction caused by inflammation and cell damage. In September 2022, Resverlogix (Alberta, Canada), which partnered with EVERSANA (Chicago, Illinois) to develop apabetalone, announced that the drug’s future COVID-19–related clinical development will focus on treating and preventing PCC. A phase 3 study protocol of apabetalone for this indication is being finalized and the trial is planned to begin in the first half of 2023. By blocking BET proteins, apabetalone might reduce the production of dysregulated proteins that might initially help resolve the acute COVID-19 disease state, but contribute to chronic symptoms after acute COVID-19 infection, potentially improving health outcomes for patients with PCC.

We were unable to find information regarding the potential cost of apabetalone to treat PCC.

Commentary

Effective interventions are needed to treat the growing number of patients experiencing PCC, which affects about 1 in 3 adults who had COVID-19.

Initial feedback from ECRI internal stakeholders suggested that apabetalone might improve PCC symptoms associated with chronic inflammation, one of the primary drivers of PCCs, given its purported mechanism of action. Clinical trial data are needed to determine whether apabetalone can significantly benefit patients with PCC. Research should also explore how long the functional changes in transcription might last by blocking BET proteins, and the potential safety and efficacy implications of this.

Stakeholders thought that the safety profile of apabetalone observed in previous clinical trials (e.g., in cardiovascular disease), might help expedite its clinical development for PCC compared with novel drug candidates with lesser-known safety profiles.

• Category: Treatment
• Areas of potential impact: Patient outcomes, health care disparities, health care costs

Description

EB05 (Edesa Biotech, Inc, Ontario, Canada) is a monoclonal antibody under development as a single-dose treatment for adult patients who are hospitalized with COVID-19–related respiratory disease.

A leading cause of death in patients with COVID-19 is acute respiratory distress syndrome (ARDS), resulting from the overproduction of proinflammatory cytokines. The SARS-CoV-2 spike protein is thought to bind and activate TLR4, an innate immune receptor on the cell surface that triggers an inflammatory response. This might prolong or exaggerate innate immune responses during COVID-19, leading to ARDS, critical lung injury, organ failure, and death. EB05 inhibits TLR4 activation and its inflammatory pathway, which might prevent further lung injury and reduce the risk of ventilation or death.

The developer reported updated results from a phase 2 trial of EB05 to treat COVID-19 in 237 adults who were hospitalized with COVID-19 (33 patients critically ill and 204 patients with severe disease) on September 22, 2022. Patients with COVID-19 who were critically ill received a single intravenous infusion of EB05 in addition to standard of care (SOC) had a mortality rate of 7.7 percent, compared with 40 percent in those given placebo and SOC, an 84 percent reduction in the risk of death at 28 days.

Edesa Biotech has submitted a phase 3 trial protocol design and statistical plan to the FDA to evaluate the efficacy of EB05 in patients critically ill with COVID-19. Phase 3 trials using this trial design are ongoing in Canada, Colombia, and Poland.

We were unable to find information regarding the potential cost of EB05 to treat COVID-19–related respiratory disease.

Commentary

EB05 might improve health outcomes for patients hospitalized with COVID-19–related respiratory disease by mitigating the hyperinflammatory immune response associated with severe illness and death. Phase 2 results show a clinically meaningful reduction in mortality for patients with COVID-19 who were critically ill compared with placebo, and clinical improvement in patients with COVID-19 who were severely ill.

Feedback from ECRI stakeholders suggested that, if effective, EB05 could be a beneficial addition to the SOC for patients with COVID-19 who are critically ill, potentially improving patient health outcomes and reducing health care costs and burden on the health care system. EB05 has the potential to provide effective treatment for this subset of patients with poor prognosis despite the many therapies investigated during the COVID-19 pandemic.

Stakeholders also thought EB05 might increase health care disparities if its cost is high, and it is not accessible. Some stakeholders were concerned that approval for phase 3 trials is still pending and that the timing of prospective FDA regulatory events might continue to limit the availability of EB05 for some time.

• 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.

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.