PCORI Biweekly COVID-19 Scan: Colchicine, Monoclonal Antibodies for Treating Patients with COVID-19 (October 1-14, 2020)
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.
Drugs modeled on natural immune responses to viruses are taking center stage in the fight against COVID-19 (see Topics to Watch). The National Institutes of Health (NIH) announced a phase 2 trial investigating the antibodies risankizumab (Boehringer Ingelheim) and lenzilumab (Humanigen).
These treatments show promise, but obstacles remain. Eli Lilly’s antibody trial was paused on October 13, 2020, due to safety concerns. Researchers are investigating to determine whether the safety issues are related to the treatment group or the placebo group.
Short supply and high costs could pose additional obstacles. Regeneron estimates that enough doses to treat up to 300 000 patients with REGN-COV2 will be available in coming months. But, this might not be enough, given the number of COVID-19–related hospitalizations in the United States. Less expensive, widely available treatments, such as colchicine (see Topics to Watch), might reach more people; however, the disparities in care that many are already experiencing could increase if expensive treatments with limited availability turn out to be more effective.
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.
Colchicine to Treat Patients Hospitalized with COVID-19
At a Glance
- Colchicine is an oral drug approved for treating gout and familial Mediterranean fever that is being investigated for treating COVID-19 because of its purported anti-inflammatory and antiviral properties.
- An open-label, phase 2 clinical trial conducted in Greece found that colchicine treatment added to standard care provided a longer time before patients’ symptoms worsened, compared with standard care alone. A cohort study also found that hospitalized patients given colchicine and standard care were about 5 times as likely to be discharged and more than 3 times less likely to die, compared with standard care.
- Colchicine is being investigated in 4 ongoing clinical trials in the United States, including a trial enrolling about 6000 outpatients, with primary study completion expected in December 2020.
- One course of colchicine for treating COVID-19 costs about $80 to $150.
Colchicine is an oral drug that has been approved by the US Food and Drug Administration (FDA) for treating gout and familial Mediterranean fever. It is being investigated as a repurposed treatment for COVID-19 because of its anti-inflammatory and antiviral properties. According to investigators, colchicine might dampen COVID-19–related cytokine storm, decreasing inflammation as well as preventing cardiovascular complications, although more research is needed.
Data published in June 2020 from an open-label, phase 2 clinical trial of 105 Greek patients hospitalized with COVID-19 found that colchicine treatment added to standard care provided a longer time before patients’ symptoms worsened than standard care alone. A cohort study published in September 2020 found that hospitalized patients with COVID-19 given colchicine were about 5 times as likely to be discharged and were more than 3 times less likely to die compared with standard care.
Colchicine is being investigated in 4 ongoing clinical trials in the United States. One of these trials is a phase 3 randomized controlled trial enrolling 6000 high-risk outpatients with coronavirus infection; primary completion is expected in December 2020.
Based on trial dosing and colchicine pricing, 1 treatment course costs about $80 to $150.
Colchicine is an FDA-approved drug with established efficacy and safety for 2 inflammatory conditions. As such, it is already widely diffused into the US health care system and is available as a generic drug, which might reduce treatment costs compared with other COVID-19 treatments.
ECRI internal stakeholders providing early feedback on this topic thought that the initial clinical study data were promising, and that colchicine has potential to substantially improve patient health outcomes. Stakeholders thought colchicine is relatively inexpensive, which might reduce health care costs, compared with potentially more expensive treatments. The drug could help reduce health disparities by being accessible to more patients.
Known side effects of colchicine include nausea, vomiting, and diarrhea, which might be especially harmful in those with COVID-19, because dehydration is thought to worsen disease severity. More data from larger trials are needed to assess colchicine's safety and efficacy in patients with COVID-19.
- Area of Potential Impact: Patient outcomes, health care delivery and process, health care costs
- Category: Treatments
Monoclonal Antibodies Targeting the SARS-CoV-2 Spike Protein for Treating COVID-19
At a Glance
- Laboratory-grown neutralizing monoclonal antibodies target the coronavirus spike (S) protein, responsible for virus binding and entry into host cells. Treatment with these neutralizing antibodies might confer short-term, passive immunity against coronavirus infections, improving patient outcomes.
- Preliminary results from Eli Lilly found that nonhospitalized patients given neutralizing antibodies plus standard care had lower virus counts at day 11 and a lower hospitalization rate, compared with placebo plus standard care through day 29. Also, treatment with a cocktail of 2 antibodies reduced virus counts, improved symptoms, and reduced COVID-related hospitalization and emergency room visits, compared with placebo plus standard care.
- Regeneron reported nonhospitalized patients without detectable plasma coronavirus antibodies before treatment gained the most. These patients experienced reduced virus counts, shorter time to symptom alleviation, and fewer medical visits when given a 2-antibody cocktail, compared with placebo.
- Eli Lilly and Regeneron have submitted requests to the FDA for emergency use authorizations for LY-CoV555 monotherapy and REGN-COV2 dual-antibody treatment.
The coronavirus S protein is expressed on the virus’s surface and is responsible for binding and entry into host cells. Therefore, treatment with laboratory-grown neutralizing monoclonal antibodies targeting the S protein might interfere with this process and provide short-term, passive immunity against coronavirus infections, improving patient outcomes. Multiple neutralizing antibody candidates are in clinical trials, and 2 companies have reported initial results.
One of these companies, Eli Lilly, on September 16, 2020, reported on 450 nonhospitalized patients with mild to moderate COVID-19 symptoms in the BLAZE-1 trial that were given 1 of 3 LY-CoV555 doses or placebo within 3 days of positive test sample collection. Patients given the middle dose had lower virus counts at day 11 and a lower hospitalization rate through day 29. Additionally, an October 7, 2020, news release reported that treating 112 patients with 2 antibodies (LY-CoV555 and LY-CoV016) lowered virus counts, improved symptoms, and reduced COVID-related hospitalization and emergency room visits compared with these outcomes in 154 patients given placebo.
And on September 29, 2020, Regeneron reported on 275 nonhospitalized patients with or without symptoms in a phase 1/2/3 trial given standard care plus a 2-antibody cocktail (REGN-COV2) or placebo within 3 days of positive test sample collection. In this trial, patients without detectable plasma coronavirus antibodies before treatment gained the most in terms of reduced virus counts, shorter time to symptom alleviation, and fewer medical visits.
Early results with neutralizing antibodies in nonhospitalized patients are encouraging; however, questions remain regarding which patients should receive treatment. These issues include whether use should be restricted to patients lacking detectable coronavirus antibodies and whether neutralizing antibodies are effective in hospitalized patients with COVID-19. Additionally, questions remain about whether antibody cocktails improve outcomes relative to single antibodies, as well as the impact of antibody cocktails on supply levels and costs and on reducing viral resistance.
Early feedback from ECRI internal stakeholders suggests that neutralizing antibodies have substantial potential to improve patient health outcomes. However, stakeholders were concerned about the risk of neutralizing antibodies causing adverse immune reactions, which may be particularly concerning in COVID-19 patients because of the role of abnormal immune responses in the disease.
Stakeholders thought neutralizing antibodies would be costly, which could limit access for underinsured patients and lead to coverage disputes as well as disparities.
- Area of Potential Impact: Patient outcomes, population health, health care costs
- Category: Treatments
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 20, 2020
What's Happening at PCORI?
The Patient-Centered Outcomes Research Institute sends weekly emails about opportunities to apply for funding, newly funded research studies and engagement projects, results of our funded research, webinars, and other new information posted on our site.