On May 1, 2020, the U.S. Food and Drug Administration (FDA) approved an emergency use authorization (EUA) for the treatment of severe coronavirus disease 2019 (COVID-19) with the intravenous antiviral drug remdesivir, developed by Gilead Sciences. The EUA permits the treatment of adults and children hospitalized with severe COVID-19, which is defined as depressed levels of oxygen. Japan’s Ministry of Health, Labour and Welfare subsequently granted remdesivir a similar Special Approval for Emergency, and authorization is expected soon from the European Medicines Agency. The authorizations for emergency use followed swiftly after randomized controlled clinical trials with remdesivir provided the first glimmer of hope that the virus responsible for the ongoing global pandemic, SARS-CoV-2, could be amenable to therapeutic interventions.
In late April, results from three important phase 3 randomized controlled trials provided promising evidence that remdesivir could serve as a component of the medical toolbox against COVID-19. In the earliest double-blind placebo-controlled trial, adults hospitalized with COVID-19 in Wuhan, China, received either a 10-day course of remdesivir or a placebo control, as well as standard of care treatment. Because the epidemic in Wuhan was waning at the time, researchers were unable to recruit enough patients to establish statistical significance and the results were inconclusive. The second trial was an open-label trial conducted by Gilead to compare outcomes in patients receiving a 5-day course or a 10-day course of remdesivir plus standard of care. In a study of 397 patients, the time to clinical improvement was not significantly different between the two groups, suggesting that clinicians could routinely use the shorter course of treatment. In the third trial, a double-blind placebo-controlled study conducted by the U.S. National Institute of Allergy and Infectious Diseases, patients receiving a 10-day course of remdesivir had a median time to clinical improvement of 11 days, compared to 15 days for those receiving placebo and standard of care. Remdesivir also delivered a slightly decreased rate of mortality in this study, but the outcome was not statistically significant. While remdesivir is not a cure, nevertheless the NIAID trial demonstrated that it is the first effective antiviral therapeutic in the toolbox against COVID-19.
The case of remdesivir also clearly illustrates that various hurdles in licensing, manufacturing, and distribution must be overcome to ensure adequate and equitable access to COVID-19 medical products. In the U.S., the EUA allowed for treatment of more patients outside of clinical trial settings, but physicians immediately criticized the lack of transparency in how hospitals were selected to receive doses of the therapeutic. Massachusetts General Hospital was the only hospital in the city of Boston to receive an allocation and yet smaller community hospitals in the suburbs with fewer numbers of COVID-19 patients also received treatment doses. Such an unbalanced distribution threatens to exacerbate the inequities in COVID-19 impact already being experienced by racial and ethnic minorities and lower-income communities across the country.
Following public condemnation, the federal government issued a statement on May 9 saying that future allocations of the drug would be sent to state health departments over the subsequent six weeks for distribution to hospitals based on local need. But HHS did not explain how it was determining each state’s treatment allocation or the order of shipment. Axios reported that the botched distribution was the result of a lack of coordination between HHS and the Federal Emergency Management Agency (FEMA), use of outdated COVID-19 disease burden data, and the ongoing dysfunction and lack of accountability that has come to represent much of the federal government’s COVID-19 response. It will be impossible to supply the entire country instantaneously with any approved treatment or vaccine, and therefore it is imperative that the federal government present to the American people clear and transparent plans for the prioritization and distribution of COVID-19 medical products that take into account communities’ disease burden, risk profile, and level of need.
Globally, the need for adequate and equitable access to treatments, vaccines, diagnostics, and other medical equipment for COVID-19 is significant and the challenges are numerous. In the early weeks of the pandemic, there was a scramble on the international market for diagnostic test materials, personal protective equipment, and ventilators that allowed countries with greater purchasing power to squeeze out countries with less funding and political clout. While the last few years has seen a trend in the rise of nationalistic governments, a global infectious disease pandemic will force governments to confront the stark reality that no one country is safe from COVID-19 until all are safe. Instead of enabling some countries to commandeer life-saving supplies, there must be fair, equitable, and affordable access to the medical products and supplies that will end this pandemic.
There is a growing consensus among political leaders and civil society that COVID-19 medical products are global public goods and must be made available to all globally who need them. Pharmaceutical company executives are beginning to recognize this new reality. Gilead has long been the target of criticism by global health activists for the pricing of its HIV and hepatitis C drugs. In early March, Gilead sought and received orphan drug designation from FDA, a regulatory mechanism designed to accelerate the development of drugs for diseases with fewer than 200,000 patients. While there were fewer than 200,000 patients at the time in the U.S., it was clear that the potential treatment population for COVID-19 would be very large and that regulatory authorities were working to support accelerated development of COVID-19 therapeutics. Under withering criticism, Gilead requested that FDA rescind the orphan drug designation. It opted to donate its initial supply of 1.5 million doses of remdesivir.
After receiving the EUA, Gilead affirmed that its “overarching goal is to make remdesivir both accessible and affordable to governments and patients around the world.” The company has since issued non-exclusive voluntary licenses to five generic companies in India and Pakistan to manufacture remdesivir for distribution to 127 designated low and middle-income countries. Under these licenses, generic companies will set their own price for the product and will not pay Gilead a royalty until WHO declares an end to the pandemic or until another COVID-19 treatment or vaccine is approved. These licenses represent an important step forward, although there has been some criticism that the list of countries does not include populous middle-income countries like Brazil and Mexico and thus leaves out a sizable percentage of the world’s poor.
During this week’s abbreviated World Health Assembly that occurred on May 18th and 19th—the annual meeting of all Member States of the World Health Organization (WHO)—Member States adopted a broad resolution on COVID-19 response that included a commitment to ensure global access to COVID-19 medical products. Member States agreed to the resolution calling “for the universal, timely and equitable access to and fair distribution of all quality, safe, efficacious and affordable essential health technologies and products.” The Assembly also requested that the Director-General Dr. Tedros Adhanom Ghebreyesus “identify and provide options…to be used in scaling up development, manufacturing and distribution capacities needed for transparent equitable and timely access to quality, safe, affordable and efficacious diagnostics, therapeutics, medicines, and vaccines for the COVID-19 response.” The U.S. government disassociated itself from certain parts of the resolution, including the sections about ensuring equitable access. The WHO has already been in discussions with Member States and other stakeholders about creating a platform to facilitate the voluntary pooling and licensing of patents for COVID-19 technologies. WHO plans to launch the platform at the end of May 2020. There will likely be resistance from the U.S. and others, but there is a growing global consensus that this is not a time for business as usual.