citation

Katherine Bliss and J. Stephen Morrison. "Covid-19 Therapies at the Crossroads." CSIS Commission on Strengthening America's Health Security, Center for Strategic and International Studies, July 06, 2022. Accessed July 13, 2022. https://healthsecurity.csis.org/articles/covid-19-therapies-at-the-crossroads/

The CSIS Commission on Strengthening America’s Health Security recommends accelerating U.S. leadership and global action to ensure availability and uptake of Covid-19 therapies, including through efforts to scale financing, sustain R&D, and strengthen health systems.

Photo Credit: Photo: JONATHAN NACKSTRAND/AFP/Getty Images

Photo: CHANDAN KHANNA/AFP/Getty Images

Overview

The last two and a half years of the global Covid-19 pandemic have witnessed unprecedented research and development collaboration that has resulted in the availability—in record time—of new vaccines. Significant gains have also been achieved in developing treatments that reduce the severity of illness for high-risk patients. With Covid-19 vaccine coverage in many low- and middle-income countries stuck at low levels, far below the 70 percent target set by the World Health Organization (WHO), therapies have become an even more central—and urgently needed—tool to mitigate the potential for a surge in infections and hospitalizations that can rapidly overwhelm fragile health systems and to reduce the transmission of virus among susceptible populations. To date, the Covid-19 therapies research landscape has shown great promise, with clinical trials of existing and new monoclonal antibodies, antivirals, and drug combinations leading to a diverse set of treatments that have been granted emergency authorization.

But the agenda to advance therapies is fraught. With so much early attention focused on vaccines, the effort to develop Covid-19 therapies was more limited and less well coordinated. Considerable progress has now been made, but there is a significant risk of stagnation imperiling efforts to scale production and delivery of therapies, in combination with diagnostics. There is also the very real possibility of interrupted progress in the United States and other wealthy countries and of even more pronounced setbacks in low- and middle-income countries where programmatic implementation capacity, demand, and financing all remain highly problematic. Each new mutation of SARS-CoV-2 threatens to undermine the efficacy of existing therapies and points to the importance of sustained investments in research and development to ensure continual innovation in next-generation treatments and availability of a range of options to serve diverse populations. Even as multiple highly transmissible sub-lineages of the Omicron variant circulate, skepticism persists that a “test and treat” approach in low- and middle-income countries is warranted or feasible in the near and even medium term. Both high-level political will and national and international financial commitments fall far short of what is required to ensure equitable and timely access to Covid-19 therapies. Despite several years of discussion, there is still no agreed, concrete plan for coordinating, scaling, financing, and holding to account an international mobilization to implement Covid-19 antiviral treatment in low- and middle-income countries.

In the fall of 2021, the CSIS Commission on Strengthening America’s Health Security convened a Covid-19 Therapies Working Group to develop policy recommendations aimed at strengthening U.S. leadership and global action to ensure access to and uptake of Covid-19 therapies worldwide. Drawing on insights gleaned through a series of private meetings and roundtable discussions with pharmaceutical manufacturers, government officials, representatives of multilateral organizations, and nongovernmental organizations, the working group recommends accelerated U.S. leadership to mobilize adequate new resources; ensure continued research and development into the next generation of Covid-19 therapies; create a scalable, accountable, international financing mechanism; strengthen health systems; create a more favorable marketplace; and develop communications to improve the understanding by both patients and providers of the uses and benefits of Covid-19 therapies.

The Challenges

Since 2020, the search for new Covid-19 therapies has primarily involved assessing older, existing products for new uses, with some research and development into innovative therapeutic approaches. Yet even as repurposed and novel products have received Emergency Use Authorization (EUA) for treating Covid-19, the research and development process has faced multiple challenges that compound limited political will and long-term financing. These include inadequate infrastructure and capacity for clinical trials; complicated regulatory processes; a lack of timely data sharing; weak market signals to stimulate production and distribution globally; misinformation about the risks and benefits of Covid-19 therapies; gaps in access to healthcare; and a lack of guidance regarding how to assess the appropriateness of treatment options and eligibility criteria, leading to poor understanding among healthcare providers regarding the implementation of test and treat approaches.

Early in the pandemic, research collaborations, including the WHO’s Covid-19 Solidarity Therapeutics Trial, the European Union’s “Therapeutics Innovation Booster,” and the Accelerating Covid-19 Therapeutic Interventions and Vaccines (ACTIV) partnership, led by the National Institutes of Health, were launched to coordinate and accelerate the development and testing of promising new products. In China and elsewhere, universities and research consortia have also brought promising treatment candidates forward. While several monoclonal antibody treatments have been granted EUA, new sub-lineages of the SARS-CoV-2 Omicron variant have rendered some of these ineffective, resulting in the authorization being removed. In the United States and elsewhere, new oral, tablet form, antiviral preparations—Merck’s Lagevrio (molnupiravir) and Pfizer’s Paxlovid (nirmatrelvir and ritonavir) —have been granted EUA, alongside Gilead’s Veklury (remdesivir), an older drug that must be given through infusion and is approved by the FDA for treatment of Covid-19.

But sustaining a research agenda also relies on streamlining and integrating regulatory processes, which can be time-consuming and complicated, particularly when national governments have different requirements for labeling, packaging, and marketing products. In the United States, the Food and Drug Administration (FDA) established the Coronavirus Treatment Acceleration Program (CTAP) to facilitate availability of drugs capable of treating Covid-19, providing guidance and prioritizing review of Covid-19-related products. In the European Union, the EU Strategy on Covid-19 Therapeutics outlines a strategy for ensuring accelerated review, provides for flexibilities in terms of packaging and labeling requirements, and allows for conditional marketing authorizations, with the European Medicines Agency (EMA) working closely with member countries’ regulatory authorities to secure approval for clinical trials. In Latin America and the Caribbean, 20 countries use regulatory reliance to adopt marketing authorizations from the U.S. FDA, the EMA, and Health Canada, while others in the region also rely on regulatory guidance from Argentina, Australia, Brazil, Chile, Japan, Mexico, and Switzerland. In other regions, such as sub-Saharan Africa, regionally fragmented approaches to drug authorizations have been alleviated to some extent through the WHO prequalification process.

Yet overcoming regulatory hurdles does not guarantee that authorized products will be easily manufactured or made available in a transparent and equitable fashion. In 2021 President Biden and EU president Ursula von der Leyen launched the EU-U.S. Covid-19 manufacturing and supply chain task force, with subsequent plans to “work towards aligning R&D [research and development] investments with manufacturing and manufacturing capabilities development.” In April 2021, Merck announced bilateral voluntary licenses with several generic manufacturers, followed by the announcement last October with the Medicines Patent Pool (MPP) of a licensing agreement to authorize production of molnupiravir in more than 100 countries. The MPP has also negotiated with 36 generics producers to manufacture generic versions of Pfizer’s Paxlovid to be sold in 95 low- and middle-income countries. Recently the Clinton Health Access Initiative (CHAI) announced that it had also negotiated agreements with generics suppliers “to make generic Paxlovid (nirmatrelvir/ritonavir -NIR/r) available . . . at under US$25 per treatment course for treatment of COVID-19 in high-risk patients.” Recent analyses in the New York Times and elsewhere, however, have suggested that the vast majority of Paxlovid and molnupiravir purchases have been made by high-income countries, raising the likelihood that the inequities and delays seen in vaccines, and experienced two decades ago in the midst of the HIV pandemic, will be repeated with respect to Covid-19 therapies. Affordability questions, limited demand by some governments that have not yet prioritized therapeutics within their pandemic response, and the complexities of manufacturing, which can make it difficult for some generics producers to enter the market, all point to the importance of an integrated approach to research, development, production, and distribution.

In addressing challenges related to making Covid-19 tools available worldwide, the second Global Covid-19 Summit, hosted by President Biden on May 12, focused in part on galvanizing global engagement and commitments in support of equitable distribution of Covid-19 therapies. The summit secured more than $3 billion in new funding pledges, but those focused on Covid-19 therapies, including test and treat options, totaled a mere $122 million and did not advance planning for greater global coordination in planning for and expediting the delivery of Covid-19 treatments to the most vulnerable communities. Such modest U.S. commitments toward the global distribution of Covid-19 therapies reflect tension between domestic and foreign priorities and, most importantly, reflect the recent inability of Congress to secure additional, essential resources for both the domestic and overseas Covid-19 response. They may also reflect a fundamental lack of understanding of the vital role of therapeutics and the importance of a multifaceted strategy, rather than one that solely relies on vaccines. Without significant new funding, U.S. leadership—and the ongoing response—will remain heavily constrained.

At the summit, the United States announced an investment of $20 million in American Rescue Plan Act funds to pilot Covid-19 test and treat strategies in up to eight countries, with the U.S. Agency for International Development (USAID) leading the work in coordination with the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) and other government programs. Merck committed to make “two million patient courses of Merck’s investigational oral antiviral COVID-19 medicine, LAGEVRIO™ (molnupiravir), available to USAID at Merck’s best access price to increase access in lower-income countries.” And Pfizer said that it would provide the two components of Paxlovid, nirmatrelvir and ritonavir, “to countries in need, including emerging economies in Sub-Saharan Africa, Asia, and the Americas.” While the summit saw little discussion and no commitments regarding monoclonal antibodies, the U.S. FDA did commit to continue prioritizing the review of “Covid-19 therapeutics, including applications seeking tentative approval of generic products.”

Ensuring people are able to make use of Covid-19 medicines once they are available is a final piece of the puzzle. One necessary step is finding ways to ensure supply meets demand. As recently as February there was a mismatch in the United States between the locations of reported Covid-19 cases and the availability of antiviral and monoclonal antibody therapies. In some places, monoclonal antibodies, which require infusions, are not easily delivered because of limited clinical space or a dearth of health workers trained to administer them. And because WHO guidance on using monoclonal antibodies continues to evolve in response to the emergence of new variants that are not susceptible to existing preparations, ongoing communication with providers is critical. Yet even though oral antivirals might be far simpler to administer in places where health systems are fragile, there is considerable confusion among healthcare providers about their use and how to prioritize treatments for people at highest risk of severe illness, hospitalization, and death. And since both antivirals and monoclonal antibody treatments must be used within a short period after symptom onset, it is important to ensure both the availability of additional treatment options appropriate for use in settings where testing and access to providers who can prescribe the products may be limited, underscoring the importance of continued investment in research and development to secure a broad range of therapeutic interventions, including for early treatment and prophylaxis.

Recommendations

  • Increase U.S. leadership and diplomatic engagement to secure resources. At the summit, there were important announcements made by manufacturers Merck and Pfizer, along with CHAI, to make antiviral products available at lower prices for low- and middle-income countries. More recently, Pfizer has announced “An Accord for a Healthier World,” committing to make all of its patented medicines, including Paxlovid, available to 45 low- and lower-middle income countries at not-for-profit prices. An urgent priority is that the White House and Congress reach a consensus on major additional U.S. financial commitments for domestic and global efforts related to Covid-19 response, including supporting research and development into next-generation therapies, as well as procurement and distribution of the full range of therapies. Aggressive U.S. diplomatic outreach in the run up to the G7 and G20 meetings is essential to secure higher commitments by other countries to support globally equitable access to Covid-19 therapies.
  • Sustain research and development into next-generation Covid-19 therapies to ensure a range of options that keep pace with the evolution of the virus and that are capable of meeting the needs of diverse global populations. Researchers, private sector research and development companies, governments, and international consortia involved in research on Covid-19 therapies should understand the barriers to equitable access across diverse settings within low-, middle-, and high-income countries; prioritize the development of products that provide a diversity of options to address these barriers; and take global equity and access considerations into account at the earliest stages of product design and development. In addition to scaling up access to oral treatments, finding ways to more easily and affordably deliver monoclonal antibody therapies to populations in low- and middle-income countries will be important. Yet, it is also essential at this early stage to create financing and regulatory incentives for companies to assess how products made by different manufacturers can be used in combination or whether they can be used prophylactically. It is also important to continue to streamline regulatory processes through greater use of new regional approaches including the African Vaccine Regulatory Forum (AVAREF), the African Medicines Agency, and, critically, WHO prequalification to accelerate the availability of new medicines as well as quality-assured generics that meet the criteria of such global procurement organizations as UNICEF and the Global Fund.
  • Prioritize the development of a global mechanism that can coordinate, scale, finance, and hold to account an international mobilization. Within the U.S. government, this will involve achieving better unity of U.S. efforts across different agencies. USAID is well situated to lead U.S. bilateral efforts to support countries in distributing Covid-19 therapies and can incorporate funding such activities into its existing Covid-19 response strategy. But in doing so, it should work in coordination with the U.S. Department of Health and Human Services (HHS) and other federal agencies. The U.S. Biomedical Advanced Research and Development Authority (BARDA) should continue to lead U.S. efforts to accelerate testing and treatment development and support expanding the industrial base for manufacturing in the United States.

The U.S. Centers for Disease Control and Prevention (CDC) can play a key role in working with ministries of health and other partner organizations to research, standardize, and promote appropriate testing in countries around the world to help ensure the effective use of therapies. The U.S. Department of Defense has considerable planning, contracting, and logistics capabilities to offer to the U.S. international response. PEPFAR has considerable experience delivering antiviral therapies. Its role leading the U.S. representation on the board of the Global Fund, which currently finances the greatest amount of non-vaccine Covid-19 interventions for low- and lower-middle-income countries, points to a prominent role for PEPFAR in helping to ensure U.S. bilateral approaches to Covid-19 testing and treatment complement multilateral agencies’ strategies. As the United States looks ahead to the Global Fund replenishment, which it will host in September, it will be important that it continue to encourage other pledging countries to join it in reaching the Global Fund’s $18 billion goal for the next work phase.

  • Strengthen health systems and shape the marketplace. At present, demand for antivirals outside the high-income countries remains lukewarm, in part because government procurers in low- and middle-income countries may not perceive a need for them and also because under-resourced health systems may not be capable of ensuring patients can be diagnosed and initiated on treatment within the short window following symptom onset. New initiatives, such as the pilot projects led by the partnership between the Open Society Foundations, the Covid Global Accountability Platform, and CHAI seek to demonstrate the potential for scaling up therapies in low- and middle-income countries and can shed light on the factors that hamper or encourage successful distribution and uptake of therapeutic approaches. Actors including the U.S. government and other organizations that procure pandemic therapies could serve as large volume buyers to ensure production, particularly of quality-assured generic products from the generic licensees. Transparent price tiering should be encouraged to incentivize purchase orders by countries at varying income levels.
  • Accelerate the establishment of a global communications hub to ensure patients and providers have access to accurate information regarding Covid-19 testing and treatments. Communicating the benefits, eligibility criteria, and uses of novel products will be critical if providers are to be confident prescribing new products and patients are to feel comfortable taking them. The United States can also share lessons learned from the launch of its own test to treat model, which is gaining momentum.

Signatories

Asaf Bitton is the executive director of Ariadne Labs, a joint center for health systems innovation at Brigham and Women’s Hospital and the Harvard T.H. Chan School of Public Health.

Katherine E. Bliss is a senior fellow and director of immunizations and health systems resilience with the CSIS Global Health Policy Center.

Rachel Cohen is the regional executive director for the Drugs for Neglected Diseases initiative (DNDi).

Rear Admiral (Ret.) Thomas R. Cullison is a senior associate (non-resident) with the CSIS Global Health Policy Center. During his 38-year naval career, culminating as deputy surgeon general of the Navy, he was active in disaster management, international health engagement, graduate medical education, and health policy.

Julie Louise Gerberding is the chief executive officer of the Foundation for the National Institutes of Health and cochair of the CSIS Commission on Strengthening America’s Health Security.

Nikolaj Gilbert is the president and chief executive officer of PATH and managing director of PATH’s Swiss subsidiary, Foundation for Appropriate Technology in Health.

Mark Godfrey is the senior director of global public policy at Eli Lilly and Company.

Rajesh Gupta is the vice president of the global health portfolio and public-private partnerships at Vir Biotechnology Inc.

Margaret “Peggy” Hamburg serves as chair of the NTI bio Advisory Group and previously served as commissioner of the U.S. Food and Drug Administration (FDA) from 2009 to 2015.

Ambassador Karl Hofmann is the president and CEO of Population Services International (PSI) and was previously a career American diplomat for 23 years.

Yanzhong Huang is a senior fellow for global health at the Council on Foreign Relations.

Heather Ignatius is the managing director of advocacy and public policy at PATH.

Seth G. Jones is a senior vice president, Harold Brown Chair, director of the International Security Program, and director of the Transnational Threats Project at CSIS.

Jenelle Krishnamoorthy is a vice president and head of global public policy and international affairs at Merck & Co., Inc.

Ramneek Mahal is the vice president of global corporate government affairs and policy at GlaxoSmithKline (GSK).

J. Stephen Morrison is a senior vice president at CSIS and director of its Global Health Policy Center.

U.S. Senator Patty Murray is the senior senator from the state of Washington and currently serves as chair of the Senate Health, Education, Labor, and Pensions (HELP) Committee.

Jamie Nishi is the executive director of the Global Health Technologies Coalition.

Carolyn Reynolds is cofounder of the Pandemic Action Network and a senior associate (non-resident) with the CSIS Global Health Policy Center.

Paul Schaper is the executive director of global public policy at Merck & Co., Inc.

Stephanie Segal is a senior associate (non-resident) with the CSIS Economics Program.

Jeffrey Sturchio is a senior associate (non-resident) with the CSIS Global Health Policy Center.

Prashant Yadav is a senior fellow at the Center for Global Development and affiliate professor of technology and operations management at INSEAD.

Juan Zarate is the global co-managing partner and chief strategy officer of K2 Integrity and a senior adviser (non-resident) with the CSIS Transnational Threats Project and Human Rights Initiative.

This commentary conveys a majority consensus of the signatories who are participating in their individual capacity, not as representatives of their respective organizations. No expert is expected to endorse every single point contained in the commentary. In becoming a signatory to the commentary, experts affirm their broad agreement with its findings and recommendations. Language included in this commentary does not imply institutional endorsement by the organizations that participants represent.

Special thanks to the participants in the CSIS commission’s meetings on Covid-19 therapies in the winter and spring of 2022; to Humzah Khan and Michaela Simoneau for their support of the CSIS Commission on Strengthening America’s Health Security and the commission’s Covid-19 Therapies Working Group; and to Courtney Burks for her research assistance.

This commentary is a product of the CSIS Commission on Strengthening America’s Health Security, generously supported by GSK.

Commentary is produced by the Center for Strategic and International Studies (CSIS), a private, tax-exempt institution focusing on international public policy issues. Its research is nonpartisan and nonproprietary. CSIS does not take specific policy positions. Accordingly, all views, positions, and conclusions expressed in this publication should be understood to be solely those of the author(s).

© 2022 by the Center for Strategic and International Studies. All rights reserved.

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