PCORI Biweekly COVID-19 Scan: Deupirfenidone (LYT-100) to Treat Adults, Vaccine Mandates (July 22-August 4, 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.
Viral loads in people infected with the Delta variant of SARS-CoV-2 are higher in the nose and throat. As Delta cases surge in their state, two scientists from Alabama have suggested that next-generation COVID vaccines—or, at minimum, boosters—should be intranasal. Vaccines delivered as a nasal spray could drive a different immune response that might be better at defeating the virus before it reaches the lungs. Currently, all available vaccines are intramuscular (ie, a shot in the arm muscle) which protects best against viruses that reach the lungs. Combining primary intramuscular vaccines with an intranasal booster could deliver the best of both worlds. In the United States, only three nasal vaccines are in very early clinical trials.
In the previous scan, we explored the reemergence of mask mandates as the Delta variant overtook the country. Now we see an increase in vaccine mandates (see Topics to Watch). Currently, various states, cities, and employers are creating a patchwork of individualized mandates, such as New York City’s requirement that people prove they are vaccinated before eating inside at restaurants. Meanwhile, the US Food and Drug Administration (FDA) is now expected to grant full approval to the Pfizer vaccine by early September, much earlier than originally anticipated. Many hope this move will either encourage the vaccine-hesitant to take the shot, provide a strong base of support for national vaccine mandates, or both.
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.
Deupirfenidone (LYT-100) to Treat Adults with Post-Acute COVID-19 Respiratory Complications
At a Glance
- Deupirfenidone (LYT-100) is an oral small-molecule drug being investigated to treat respiratory complications after recovery from the acute phase of COVID-19–related pneumonia.
- Deupirfenidone is a deuterated form of pirfenidone, an anti-inflammatory and antifibrotic drug approved by the FDA to treat idiopathic pulmonary fibrosis. The chemical modification purportedly slows down metabolism of the drug, which might reduce adverse effects associated with the accumulation of pirfenidone metabolites.
- Deupirfenidone purportedly reduces inflammation and cytokine release, and slows lung fibrosis, which might improve functional exercise capacity and shortness of breath, facilitating recovery from respiratory complications and preventing further lung injury.
- An ongoing phase 2 randomized clinical trial evaluating deupirfenidone in 168 adults with respiratory complications after hospitalization for COVID-19–related pneumonia has primary completion expected in August 2021.
Patients hospitalized with COVID-19–associated pneumonia might continue to experience breathlessness, lower than normal blood oxygen levels, and persistent lung infiltrates for months after their initial illness, which indicates acute lung injury and the potential for lung scarring (fibrosis). Deupirfenidone (LYT-100; PureTech Health plc, Boston, Massachusetts) is an oral small-molecule drug being investigated for treating respiratory complications after recovery from the acute phase of COVID-19-related pneumonia.
Deupirfenidone is a deuterated form of pirfenidone, an anti-inflammatory and antifibrotic drug approved by the FDA to treat idiopathic pulmonary fibrosis. The deuterated form, in which one or more hydrogen atoms are replaced by a heavier and more stable isotope of hydrogen (deuterium), is purportedly metabolized slower. This might mitigate gastrointestinal-related intolerability, pill burden, and food effect issues associated with the accumulation of pirfenidone metabolic byproducts.
Although it is unknown why certain patients experience a slower recovery from COVID-19, lung damage and fibrosis caused by viral infiltration and inflammation is thought to play a major role. Deupirfenidone purportedly reduces inflammation and cytokine release and slows lung fibrosis. This might improve functional exercise capacity and shortness of breath, resulting in a quicker recovery from respiratory complications and the prevention of further lung injury.
An ongoing phase 2 randomized controlled clinical trial comparing deupirfenidone with placebo in 168 adults with respiratory complications after hospitalization for COVID-19–related pneumonia has primary completion expected in August 2021.
The authors were unable to find information regarding the potential cost of deupirfenidone. However, it might be costly considering that pirfenidone is an expensive specialty drug with a list price of $94 000 annually when approved
Deupirfenidone is an investigational oral therapy for treating prolonged respiratory complications in patients who were previously hospitalized with COVID-19 pneumonia and required oxygen administration. If authorized by the FDA, it could be the first outpatient treatment for respiratory complications associated with long COVID.
Early feedback from ECRI internal stakeholders suggests that, if safe and effective, deupirfenidone might speed recovery from lingering respiratory symptoms, prevent additional lung damage and scarring, and improve long-term health outcomes and quality of life. The drug might decrease demands on the health care system by reducing hospital readmissions and health care costs from long-term complications. Improving lung health in the months after infection might also decrease health disparities in populations that are more likely to develop COVID-19–related complications. However, deupirfenidone might be costly and cost-prohibitive for some patients, contributing to disparities.
Deupirfenidone has the potential to become the standard-of-care for patients who show signs of fibrosis after COVID-19. However, determining which patients are eligible for this treatment might be a challenge, possibly limiting diffusion. For context, in the past 12 months, 2.5 million COVID-19–related hospital admissions have been reported in the United States. Approximately one-third of hospitalized patients develop acute respiratory distress syndrome (ARDS), and post–COVID-19 pulmonary fibrosis affects about one third of patients hospitalized with COVID-19 and ARDS. Therefore, a rough estimate of the number of patients who might be eligible for this treatment in the United States is about 275 000 patients, or about 1 in 10 cases.
- Category: Treatment
- Areas of potential impact: Patient outcomes, patient management, paradigm of care, health care disparities, health care costs
Vaccine Mandates to Prevent COVID-19
At a Glance
- Vaccine mandates are being required by many government bodies, health care companies, and universities for their constituents to limit the surge of COVID-19 cases occurring around the United States.
- People must show proof of vaccination or submit to weekly COVID-19 testing, and those unqualified for exemptions may face penalties such as job loss or removal from classes.
- Although employees have quit and filed lawsuits against such mandates, the US Department of Justice determined that vaccine requirements are legal, even though the vaccine is only authorized under Emergency Use Authorization.
- With just under 60% of eligible Americans vaccinated, vaccine mandates for employees and students have the potential to help prevent the spread of COVID-19 and keep those unable to get vaccinated or awaiting vaccination safe.
Mandatory COVID-19 vaccine requirements put forth by some states and organizations for employees, health officials, and students are additional public health measures in response to increasing COVID-19 cases and decreasing vaccination rates around the country. Vaccine mandates can be classified depending on the consequence of opting out of vaccination. Hard mandates might refuse entry to a venue or the possibility of employment for non-vaccinated persons, whereas soft mandates might impose restrictions on non-vaccinated persons such as frequent COVID-19 testing or mandatory mask use.
Early adopters of vaccine mandates included colleges and universities, health care facilities, and other private employers. More recently, the Department of Veterans Affairs became the first federal agency to mandate COVID-19 vaccines for its workers. Additionally, the federal government will require that federal workers and members of the military be vaccinated or face regular testing, social distancing, mask use, and limits to official travel.
Several state governments have also instituted soft vaccine mandates for some workers. For example, California declared that all state and health care workers must show proof of vaccination or be tested regularly. Similarly, New York City's mayor announced that workers in all city municipal offices, as well as city-operated hospitals and health clinics must get vaccinated or be tested weekly. Most vaccine mandates include the possibility of exemptions for medical or religious reasons; however, the mandates might impose restrictions on exempt persons.
Regarding the legality of mandates for vaccines lacking full FDA approval, the US Department of Justice has indicated that vaccine mandates and requirements may be legal, even when used for vaccines granted Emergency Use Authorization.
With the Pfizer vaccine potentially receiving full approval as early as September, mandating vaccines for employees and students might improve patient and population health outcomes by increasing vaccination rates throughout the country, thereby decreasing the risk of transmitting the virus and related complications.
Early feedback from ECRI internal stakeholders suggested that vaccine mandates, if effective, might streamline reopening procedures and push society toward normalcy. The mandates might also be an active public health measure against the spread of variants, such as the Delta variant, and might help prevent the rise of other variants. High vaccination rates are likely to result in reduced COVID-19 deaths and health disparities. Prevention of severe COVID-19 through vaccination might also mitigate future health care costs associated with COVID-19.
Stakeholders had concerns that mandates might result in vaccine-hesitant people quitting their jobs, which could lead to staffing issues or pushback from parents or students, which could cause health disparities. Although many governmental bodies, health care facilities, and universities are implementing this initiative, small business owners might not be subject to such mandates, decreasing the disruptive potential of the mandate.
- Category: Public Health
- Areas of potential impact: Patient outcomes, 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: August 20, 2021
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