PCORI Biweekly COVID-19 Scan: Bucillamine - Oral Anti-Inflammatory Drug, Direct-to-consumer Telehealth Platforms (November 25-December 5, 2021)

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

Bucillamine (Revive Therapeutics Ltd, Toronto, Ontario, Canada) is an oral anti-inflammatory drug under investigation to treat mild to moderate COVID-19 in an outpatient setting. Although most individuals with COVID-19 develop mild symptoms, individuals with or without high-risk conditions can develop severe, life-threatening disease. Therefore, effective treatments are needed early in the disease course to prevent disease progression, hospitalization, and death from COVID-19.

Bucillamine is a cysteine derivative with 2 thiol groups that is highly effective at restoring glutathione, a key intracellular antioxidant thought to help mitigate inflammatory reactive oxygen species generated during respiratory infections. This might help limit acute lung injury from hyperimmune responses. Research models have also shown that thiol-based drugs, including bucillamine, can decrease the binding of SARS-CoV-2 spike protein to its receptor and subsequent cellular entry. Bucillamine has a well-documented safety profile as a widely used, first-line, disease-modifying anti-rheumatic drug (DMARD) to treat rheumatoid arthritis in Japan and Korea. Thus, it is an attractive option to evaluate as a potential COVID-19 treatment.

An ongoing phase 3 clinical trial aims to assess bucillamine’s effectiveness at reducing hospitalization and death in up to 1000 patients with mild to moderate COVID-19 across 47 U.S. centers. Trial completion is expected in late November 2021. Bucillamine is taken 3 times per day at a dose of 100 mg to 200 mg, for up to 14 days. We were unable to find information regarding the potential cost of a treatment course of bucillamine in the United States. However, the current price for 100 mg tablets of bucillamine is $50 USD for 100 tablets in Japan. Based on this information, the costs might be comparable in the United States, if cleared by FDA and produced by manufacturers as a generic drug.

Commentary

The current lack of oral therapies to prevent disease progression amog nonhospitalized patients with mild to moderate COVID-19 highlights the need for new therapeutic options. Early feedback from ECRI internal stakeholders suggested that bucillamine has the potential to improve patient health outcomes if it can safely and effectively reduce hospitalizations requiring intensive treatments.

Stakeholders thought bucillamine’s  anti-inflammatory and antioxidant mechanisms sounded plausible to treat COVID-19. They noted that bucillamine could be an important addition to treatment regimens because, even if the FDA authorizes promising antiviral therapies such as molnupiravir and Paxlovid, shortages of these drugs are expected during the market rollout phase in 2022.

As an oral treatment, bucillamine might reduce current health disparities among patients with mild to moderate COVID-19 who are unable to access monoclonal antibody treatments as outpatients. Bucillamine, as a repurposed and well-tolerated drug, might be cheaper and more widely available than other new options, further reducing disparities.

Bucillamine might also reduce the burden on the health care system if there are fewer patients with worsening disease who require hospitalization. This, in turn, might mitigate costs associated with hospitalization, intensive care resource utilization, and long-term health complications.

• Categories: Treatment
• Areas of potential impact: Patient outcomes, patient management, care setting, care disparities, health care costs

Description

Direct-to-consumer telehealth platforms have integrated virtual care programs with pharmacy services to provide eligible patients with end-to-end care. ​Currently, healthcare providers have a limited number of treatment options for COVID-19 that do not require a clinic or hospital visit. ​If given in a timely manner, antiviral pills can improve health outcomes for those who test positive for COVID-19. These direct-to-consumer platforms intend to provide the infrastructure to support a complete at-home recovery from mild to moderate COVID-19 by continuing symptom management via follow-up telehealth visits. No payment or insurance co-payment is needed to enroll in these services. However, the cost for virtual visits and medications would depend on insurance coverage.

Oral antiviral treatments might reduce the spread of COVID-19 in areas with low uptake of vaccines or in cases of breakthrough infections. Broad, rapid access to effective antivirals, combined with existing foundational public health measures like vaccines and mask-wearing, would significantly reduce overall hospitalizations and deaths due to COVID-19.​

A digital health company, Truepill, plans to launch a comprehensive platform to support telehealth consultations, prescriptions, and next-day delivery of antiviral drugs such as molnupiravir and Paxlovid, if authorized. Another company, Carbon Health, also plans to incorporate oral antiviral treatments in its virtual acute COVID care program and is currently offered in 21 states and the District of Columbia. Following a visit with a virtual provider and confirmed positive COVID-19 test results, patients might receive a prescription for monoclonal antibodies or administration at select sites, an antiviral prescription, and a pulse oximeter to self-monitor their symptoms.​

Commentary

Virtual care platforms might help reduce the incidence of transmission, complications, and death due to COVID-19.

Early feedback from ECRI internal stakeholders suggested that these platforms might reduce healthcare disparities by allowing people with logistical barriers to receive treatment for mild to moderate COVID-19 at home. Since antiviral medications are most effective if administered within 3-5 days of symptom onset, these virtual care platforms could help patients initiate treatment sooner than traditional, in-person care. Virtual visit costs might be less than in-person care visits, and shifting care settings might decrease disparities and overall healthcare costs. However, it might increase health disparities if limited populations utilize these digital platforms.

The commenters also thought virtual care might help reduce the burden on the health care system if people received treatment at home. Virtual platforms would also support working adults who cannot take time off to recover at home. Increased access to antivirals might increase vaccine hesitancy, however, in people who prefer to receive medication only if they become infected with COVID-19. Given the limited projected supply of antiviral pills until early 2022, it is unclear if virtual care platforms will be widely utilized.  

• Categories: Systems and management
• Areas of potential impact: Patient outcomes, population health, care setting, treatment models, 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.