Politics, Policy & Law
Trump treatment resurfaces compassionate use quandaries
President Donald Trump’s treatment with an investigational drug from Regeneron resurfaces long-standing ethical quandaries involving compassionate use and the allocation of scarce drugs.
The REGN-COV2 cocktail from Regeneron Pharmaceuticals Inc. (NASDAQ:REGN) that the president received last week is still in clinical trials, and outside that, only available for compassionate use. Providing compassionate use to the president is certain to create demand for access to the investigational therapy.
Compassionate use policy in the U.S. has for decades been clouded by perceptions that powerful, wealthy or well-connected individuals get preferential access, and by concerns that demand for compassionate use access is fueled by exaggerated confidence in the efficacy of unapproved drugs.
Decisions about who can receive access to unapproved drugs are made by companies.
Regeneron has not announced an ethical framework for prioritizing such requests beyond stating that it will make decisions on a case-by-case basis and that prior to authorization or approval, clinical trials should be the primary form of access.
In 2013, a viral media campaign for a seven-year-old boy to get access to an unapproved drug caught the nation’s attention and led to legislation and voluntary initiatives that are intended to clarify compassionate use policies. The topic remains fraught, however, in part because of the politicization of the right-to-try movement.
Speaking on CNBC Monday, Regeneron President and CEO Leonard Schleifer said that Regeneron’s policy is to encourage patients who inquire about REGN-COV2 to enroll in a clinical trial, and that this wasn’t possible for Trump.
“Asking somebody like the president to go into a clinical trial just wasn’t practical, so giving it to him or to others who might not be able, or don’t qualify for clinical trials, is the right use of compassionate use,” he said, adding that compassionate use is appropriate “for small numbers of people, for these exceptions.”
Trump is one of a “handful” of patients, less than 10, who have received the mAb antibody cocktail on a compassionate use basis, Regeneron spokesperson Alexandra Bowie told BioCentury. “Each request is and will continue to be evaluated on its own circumstances,” she said.
Regeneron said it is making decisions about access to REGN-COV2 outside clinical trials on a case-by-case basis based on its written policy. That policy states that access to investigational medicines is intended for “patients with serious or life-threatening conditions who do not have any viable or available treatment options, and are unable to participate in ongoing clinical trials.”
Last week, an average of about 40,000 Americans per day tested positive for COVID-19. Many of them were at heightened risk because of their age and weight, and many live in places where it is impossible to enroll in a trial.
Regeneron has offered the therapy to Joe Biden, the former vice president and current presidential candidate. “We’ve been in touch with the Biden campaign just to make them aware of the compassionate use mechanism, should they need to apply,” Bowie told BioCentury.
The offer does not clarify the basis for Regeneron’s access decisions. For example, it isn’t clear whether the company is prioritizing government officials, and if so, which officials would qualify. It is also not clear whether Regeneron would provide REGN-COV2 prior to FDA authorization to Secret Service officers, White House staff — or ordinary Americans.
In addition, the decision to give Trump REGN-COV2 rather than convalescent plasma raises questions about Trump’s and his medical team’s confidence in convalescent plasma. Compassionate use, according to FDA, is reserved for patients who have no other alternatives. FDA granted emergency use authorization to convalescent plasma in August for hospitalized patients amid concerns that the authorization was politically motivated and could interfere with the completion of trials of mAbs.
Some companies have developed policies to enhance confidence that such decisions are made fairly. The Janssen unit of Johnson & Johnson (NYSE:JNJ), for example, has funded the establishment and operations of independent Compassionate Use Advisory Committees managed by NYU Langone that provide advice on the ethical allocation of investigational drugs outside clinical trials. Committee members are not informed of the names, jobs, race or other information that could bias their recommendations.
Is there equipoise?
Other comments by Schleifer to CNBC highlight long-standing concerns that patients, their families and physicians assume that unapproved therapies are effective — and that statements from companies can cause the public and physicians to draw conclusions that are not supported by evidence.
Discussing Regeneron’s efforts to enroll COVID-19 patients on randomized, placebo-controlled clinical trials rather than provide compassionate use access, Schleifer said: “Of course, the downside of that is you have a one-in-three chance of getting placebo.”
Schleifer’s choice of words rang alarm bells among bioethicists, because clinical trials are predicated on the existence of clinical equipoise — the notion that there is genuine uncertainty about the relative merits of the interventions that are offered to participants.
Alison Bateman-House, a bioethicist and assistant professor at NYU Grossman School of Medicine, noted the importance of equipoise in a note posted on Twitter: “IF WE KNOW PLACEBO IS INFERIOR, MUST STOP THE TRIAL. IF YOU DON'T KNOW THAT, PLACEBO IS NOT A BAD THING & MAY BE BETTER OVERALL THAN GETTING THE DRUG.”
The implication that the possibility of receiving a placebo is a “downside” could lead patients to avoid a clinical trial, to believe they are being treated as guinea pigs, or to seek compassionate use access.
If, as HHS Secretary Alex Azar suggested last week, mAbs to treat COVID-19 receive emergency use authorization soon, the U.S. will have to grapple with another set of ethical questions related to prioritization of access.
Regeneron has manufactured 50,000 treatment doses of REGN-COV2, and “will have 300,000 doses ready in total in the next few months,” Regeneron’s Bowie told BioCentury. These doses, which could serve only a fraction of projected numbers of COVID-19 cases, have all been sold to HHS and the Department of Defense which will be responsible for devising and implementing allocation policies.