The prospect of a COVID-19 vaccine sits at the center for the public’s hope of any return to pre-pandemic normalcy: With no effective treatments and outbreaks rising alongside relaxed lockdown rules, it’s difficult to imagine any real change without a proven vaccine.
But in a twist of dark irony, the population most susceptible to COVID-19 — elderly people, with multiple comorbidities, living in congregate settings — may not necessarily benefit from the discovery and distribution of a coronavirus vaccine.
For the Chicago-based skilled nursing operator Symphony Care Network, which has already dealt with a high-profile outbreak at one of its facilities, the knowledge that a vaccine won’t be a silver bullet was the primary motivation to participate in a clinical trial for a preventative drug under development at pharmaceutical giant Eli Lilly and Company (NYSE: LLY).
“The advanced elderly population doesn’t do particularly well with vaccines — and therefore, depending on a vaccine to stop this epidemic, and to stop this excess death rate in skilled nursing facilities, was unlikely to be an effective long-term strategy,” Dr. Alexander Stemer, co-chair of the COVID-19 task force at Symphony Care Network, told SNN last week.
Stemer joined Symphony in an advisory role in the wake of an outbreak at a facility in Joliet, Ill., and through a colleague at the National Institutes of Health (NIH) became involved with the Lilly study.
Under a pending phase-three trial announced last week, the drugmaker plans to enroll up to 2,400 residents of nursing facilities with recent COVID-19 cases to test the efficacy of LY-CoV555, an antigen that the company believes could both treat and prevent coronavirus infections.
So far, 101 facilities in California, Florida, Georgia, Illinois, Louisiana, North Carolina, Ohio, Pennsylvania, and Texas have signed up to participate, according to the federal government’s public clinical trial data; in addition to Symphony, list includes skilled nursing and assisted living properties operated by HCR ManorCare, Belmont Village, and Sunrise, among others.
The intravenous drug is based on antibodies from people who have recovered from COVID-19 infections, Stemer said. A given person’s immune system can take upwards of two weeks to develop a response to new invaders such as the novel coronavirus, but the LY-CoV555 antigen could help speed up that process.
“Now what we can do — on day one of dealing with a patient who has proven COVID-19 infection — is not have to wait two weeks for what may be a strong or weak antibody response, but immediately give them the antibody that will allow their immune system to attack this virus,” Stemer said.
This avenue of attack against COVID-19 is especially important to explore among long-term care residents because of known weaknesses in how vaccines behave among the elderly, according to Stemer.
He gave the example of the more familiar flu vaccine: Seniors over the age of 65 generally receive a high-dosage version with four times the normal amount of antigen material — and even then, it’s not an automatic option for preventing flu cases among the elderly.
“While it’s helpful in ameliorating influenza, it is not a cure-all or end-all for influenza, and that is a well-known feature of this population,” Stemer said.
But as with the use of vaccines, conducting clinical trials with older, vulnerable nursing home residents presents challenges unique to the population.
“The consensus was that nothing like this had ever been done in a skilled nursing facility before, so we needed to really start from the ground zero to understand how we were going to implement this, and what was going to be necessary to make this happen,” Stemer said.
Targeting the post-acute and long-term care population had been a top priority for Lilly researchers, according to vice president of new therapeutic modalities and COVID-19 research Andrew Adams, but there were serious concerns about the lack of a precedent for conducting clinical trials in SNFs.
“It’s hard, because the nursing home is not a space that’s typically used to being the host for clinical trials,” Adams said. “We don’t really have the type of infrastructure that we have at a research hospital or a clinical trial site, or even in an academic setting. They’re just not built to do these kinds of studies.”
So Lilly and other nursing home leaders devised a plan that will bring the necessary infrastructure to the nursing homes. The drugmaker has retrofitted a fleet of recreational vehicles to serve as mobile pharmacies where pharmacists can compound and store the experimental medication on site.
Because the drug must be administered intravenously, separate rented trucks will deliver chairs and IV poles for staff to set up temporary infusion clinics. Long dormant due to restrictions on group activities, dining areas can easily be repurposed to handle the infusion portion of the trial, Stemer noted.
Lilly will also provide on-site staff to speak with residents and their designated caregivers in order to receive informed consent for participating in the study; given the unique vulnerability of the potential subjects, Adams noted that the team was willing to spend more time on enrolling participants than usual.
“We want to follow the strictest ethical guidelines as we go into a vulnerable patient population like this,” Adams said. “We’re kind of balancing that need to go into this population — where it might be more challenging to enroll if you stick rigorously to those rules — with the fact that this is a population that has a huge unmet need.”
Further complicating the timeframe is the unpredictable nature of COVID-19 outbreaks: Because the study focuses on whether the antigen can prevent or slow the spread of infections and serious complications within the LTC setting, the teams must wait for “index cases” to pop up among participating facilities.
“There’s going to be some variability around how quickly we find out from a site that they have a positive case, how long that case has been present at the facility, and then how quickly can we dispatch the convoy to that facility to start the trial,” Adams said. “I think we’re going to learn as we go.”
In terms of results, the researchers will be looking for evidence that the residents who received the experimental treatment never developed COVID-19 in the first place, as well as improved outcomes for those who do contract the virus — for instance, residents who did not require oxygen or develop complications such as dehydration and acute kidney injury.
While Stemer expressed optimism that the antigen treatment will eventually show positive results, he emphasized that even just the prospect of a treatment can provide precious hope for residents, families, and staff during a difficult time.
“Most facilities recognize that giving patients hope, giving patients’ family hope, that there is intervention — that we have a high likelihood of being able to prevent illness and death — is a huge positive for each facility and for each company and for the industry,” Stemer said. “Because at this point, who would want their their loved one in a skilled nursing facility where the infection is transmitted, and so many people have died?”