Widespread investment in biomedical research has made many Americans tentatively optimistic about the resolution of the COVID-19 pandemic. In the public sector, the Coronavirus Aid, Relief, and Economic Security (CARES) Act has provided nearly $10 billion in funding for therapy and vaccine development through agencies like the NIH and CDC. This effort has culminated in two important milestones: the discovery that remdesivir, a drug developed to treat Ebola, reduces morbidity for patients hospitalized with severe COVID-19, and the introduction of several promising vaccine candidates into phase-III clinical trials. As of December, the FDA has issued emergency use authorizations (EUAs) for both remdesivir and Pfizer-BioNTech’s COVID-19 vaccine.
However, high costs and uncertainty about risks may hamper these interventions: Gilead has priced remdesivir at $3,120 per day despite the fact that, according to an ICER model, the drug is cost effective only up to $400 per day. And a Pew Research survey found that as many as 49% of American adults would not get a vaccine to prevent COVID-19 if it were available to them today.
These challenges pose important questions to policymakers: How will the FDA decide that the potential benefits of controversial novel drugs and vaccines outweigh their risks? And how will Medicare—tasked by the CARES Act with reimbursing COVID-related hospital fees—make expensive therapies available to uninsured essential workers who are the most vulnerable to the virus and least able to pay? Thankfully, these uncertainties are not uncharted territory:Decades of experience with HIV/AIDS have shaped regulatory institutions and provided new strategies for seeking legal remedy to reduce the price of expensive drugs.
Take the FDA for example; the Federal Food, Drug, and Cosmetic (FD&C) Act, which gives the agency its power to evaluate the safety and efficacy of drugs, has been routinely amended since it was signed into law in 1938. In the first decade of the HIV epidemic, Americans with HIV/AIDS and their advocates pushed the FDA to make experimental drugs available outside of small clinical trials. In 1987, the FDA codified the previously informal process of granting access to drugs on a “compassionate use” basis. Under the agency rule, which later became an amendment to the FD&C Act, physicians can petition for the use of experimental therapies as “treatment investigational new drugs (INDs).” Notably, the first American hospitalized with a known case of COVID-19 in Seattle, Washington was treated with remdesivir under this provision, just as people with AIDS used drugs such as AZT and ddI before formal approval.
People with HIV/AIDS succeeded again in 1988, when the FDA agreed to expedite the approval of drugs that treat “life-threatening and severely debilitating illnesses.” This “fast track” policy facilitates collaboration between regulators and industry in planning for clinical trials and gives the FDA discretion to weigh the efficacy of a drug against the severity of the disease it treats. In recent months, the FDA has granted Pfizer and BioNTech’s COVID-19 vaccine candidates, among others, fast track status.
Finally, the FD&C Act was expanded in 2004 under the Project Bioshield Act to allow the FDA Commissioner to issue emergency use authorizations in response to chemical, biological, radiological, and nuclear threats. Recipients of this dispensation are held only to a cursory evidentiary standard. As of August 2020, the FDA has used EUAs to make over 100 COVID-19-related diagnostic kits, medical devices, and therapies available to the public. Notably, remdesivir was authorized for emergency use after clinical research suggested that, when administered to hospitalized COVID-19 patients, it ameliorates the worst complications of the disease. Pfizer-BioNTech’s mRNA COVID-19 vaccine was also granted an EUA.
In some cases, however, loosening the FDA’s strict process can have dangerous consequences for patients and weaken trust in regulation. For example, in March, the FDA issued an EUA for hydroxychloroquinine—a drug already in use to treat lupus—as a treatment for COVID-19. The agency later revoked the EUA as new evidence linked the drug to “serious cardiac adverse events.” If political interference is to blame for this misstep, legislation making the FDA independent is necessary to protect objective regulatory judgement, especially in times of crisis.
Despite the broadening of compassionate use provisions in recent years, the Court has reaffirmed the FDA’s obligation to shield the public from unsafe therapies. In United States v. Rutherford, the Supreme Court ruled that the FD&C protects even terminally ill patients from drugs that do not meet safety and efficacy standards. (A similar precedent was set in 2007, when the Court refused to hear Abigail Alliance v. von Eschenbach, in which the D.C. Circuit found that cancer patients did not have the right to preserve their life by using investigational drugs under the Fifth Amendment’s Due Process Clause.)
As the COVID-19 pandemic rapidly unfolds, how can we weigh patients’ demands to try experimental therapies against regulatory bodies’ burden to protect the public from danger? While it is true that HIV/AIDS activists pushed for leniency at the FDA, they have also opposed recent “right to try” laws. Treatment Action Group (TAG), in particular, expresses concern that deregulation will lead to “harmful commercialization practices.” People with HIV/AIDS also implored researchers and regulatory officials to engage the public in decision making. In particular, their campaigns introduced community advisory boards (CABs) into clinical trial planning as a way to build trust between researchers and patients. Involving stakeholders in all steps of the research and regulatory process is especially important today, as half of Americans are hesitant to take a COVID-19 vaccine. The troubling trend of decreased transparency at federal agencies should be remedied by genuine public engagement.
Another lesson we can learn from HIV/AIDS activists is about lowering the cost of new drugs. The federal government, as part of the CARES Act, has committed to reimbursing hospitals at Medicare rates for inpatient treatment of uninsured patients with COVID-19-related health issues. The Kaiser Family Health Foundation estimated in March, soon after the Act was passed, that this measure would cost between $13.9 billion and $41.8 billion. To pressure manufacturers to lower the cost of drugs, HIV/AIDS legal strategists focus on eliciting remedies afforded by the Bayh-Dole and Hatch-Waxman Acts. In 2017, for example, four HIV/AIDS activists requested that the New York Attorney General investigate Gilead Sciences, the manufacturer of HIV-prevention drug Truvada, for anti-competitive settlements with generic drug manufacturers. In their public letter to the Attorney General, the activists allege that Gilead offered confidential settlements to generic drug manufacturers that challenged Gilead’s invalid patents on emtricitabine.
However, challenging the validity of patents may not be available to those seeking to emancipate remdesivir from Gilead today, which is protected with at least three families of patents—the oldest set to expire in around a decade. Instead, analysts have turned to a provision in the Bayh-Dole Act that allows the federal government to “march in” on an invention that was developed with public investment under certain conditions. Public Citizen estimates that taxpayers have spent over $70 million on research related to remdesivir, which may allow the federal government to license the drug’s patents “to alleviate health or safety needs which are not reasonably satisfied.” Despite pressure from thirty-four attorneys general who urged the federal government to exercise its march-in rights, there has not yet been action taken to challenge Gilead’s monopoly on remdesivir.
These strategies do not begin to cover the burden of the cost of a vaccine, and drugs like remdesivir, on the developing world. In the case of HIV/AIDS, foreign aid through the President’s Emergency Plan for AIDS Relief (PEPFAR) has been successful in distributing antiretroviral drugs to countries with the fastest growing epidemics. The program, now regarded as an exemplar in global health, is greatly aided by the United Nations-backed Medicines Patent Pool, which has facilitated the distribution of over a billion dollars of antiretroviral drugs since 2010. Following a similar model, the World Health Organization (WHO) established a COVID-19 technology access pool, but the United States, having taken steps to sever its relationship with the WHO, is not a member. A lack of coordinated government action will leave relief to the pharmaceutical giants themselves—Gilead, for one, has entered non-exclusive voluntary license agreements with generic manufacturers in Egypt, India, and Pakistan.
Reflecting on policy responses to the HIV epidemic over the last several decades makes it clear that steps beyond investment in research will be necessary to stem the spread of COVID-19. First, Congress should promote efficiency and transparency at the FDA by making it independent from the Department of Health and Human Services and the Office of Management and Budget. A group of seven former FDA commissioners provide a legislative path for achieving this, modeled after the EPA, FCC, and SSA. Second, policymakers at all levels should take steps to engage the public in decision making. Involving lay people in planning research, analyzing results, and preparing for the future could repair waning trust in a COVID-19 vaccine and improve adherence to other preventative measures. Finally, the federal government ought to leverage the Bayh-Dole and Defense Production Acts to return to the public their investment in biomedical research. These measures will ensure that intellectual property law is both rewarding innovation and facilitating the equitable distribution of essential medicines.
Clay Davis is a PhD student in sociology and Mellon Cluster Fellow in science studies at Northwestern University.