An ongoing dialogue on HIV/AIDS, infectious diseases,
November 15th, 2020
Bamlanivimab for COVID-19 — Hard to Pronounce, Even Harder to Give
The latest COVID-19 treatment made available under Emergency Use Authorization (EUA) is bamlanivimab, a monoclonal antibody developed by Eli Lilly. For now, its use will be limited to outpatients who are at high risk for severe disease and/or hospitalization.
This EUA is based on the results of the phase 2 BLAZE-1 study, in which the treatment reduced the need for hospitalization among outpatients — especially those deemed at high risk for poor COVID-19 outcomes. For this group, 3% of bamlanivimab versus 10% of placebo recipients required admission.
And yes, you read that right — bamlanivimab.
The comedians sure had a field day with this tongue-twister, and boy it’s devilishly hard to say.
But let me focus instead on the difficulty of actually giving this product to a stable, high-risk outpatient with COVID-19 — because remember, that’s the only way it’s going to help anyone.
I’ve been ruminating over the challenges of implementing this treatment for a while, ever since research began on this class of drugs. Pharmacist Tim Gauthier’s outstanding summary amplified my concerns when he wrote that the logistics of administration would be “considerable” — which could be the understatement of the year.
Why so difficult? Let me list the ways:
- Supply is limited. Even accounting for the high-risk criteria listed in the EUA, the potentially eligible recipients will greatly exceed the number of distributed doses. How bad is the mismatch? This excellent review by my ID colleagues Drs. Robert Goldstein and Rochelle Walensky estimates that based on current case counts, the supply could be exhausted in less than 2 weeks. How will we choose who gets it?
- It must be given within 10 days of symptom onset. Some experts think even 10 days is too long a wait for effective intervention — the sooner the better. While we don’t know the precise window of opportunity for benefit, remember that these monoclonal antibody treatments (from both Lilly and Regeneron) don’t appear to help people already in the hospital.
- It must be given intravenously. How many outpatient clinicians have the ability to give infusions in their clinics?
- People with early COVID-19 disease are at their most contagious. Most secondary transmissions happen between 1 day before and 5 days after the onset of symptoms, during which time respiratory viral load peaks. And this is precisely when we’ll want to bring patients in for treatment.
- Most infusion centers have a high proportion of patients who are immunocompromised. Rheumatology, GI, and neurology patients receiving intravenous immunosuppressive agents. Cancer patients receiving chemotherapy. How can we safely bring COVID-19 patients into these centers? Should we even try?
- Many infusion centers are not set up for urgent referrals. Their regular patients have regularly scheduled infusions. Even setting up an urgent dose of ceftriaxone can be challenging if the schedule is already full.
- Both the infusion and the post-treatment monitoring take a lot of time. This isn’t a simple matter of showing up, getting one quick shot, then leaving. The infusion takes 1 hour, and there is a 1-hour monitoring period afterward to ensure no severe allergic reactions ensue. Budgeting 3 hours seems about right.
- Emergency departments do not want a 3-hour treatment clogging up their patient flow — especially if they don’t get paid. Unlike most infusion centers, hospital emergency departments do have the required infection control capabilities. However, would they welcome stable COVID-19 patients sitting around getting a 3-hour treatment? If so, how many? Not only would this distract from other critical activities, but under current systems of reimbursement for ED visits, there is no guarantee that the hospital will be paid for this service.
- The formulation is tricky to prepare and not stable for very long. Tim’s a pharmacist, so let me just quote him directly: “Preparation of the IV admixture is not simple and is stable for just 7 hours at room temperature or 24 hours under refrigeration (including infusion time).” Ugh.
- Serious side effects may occur. Although not in the published paper, the package insert cites at least one case of anaphylaxis and another serious infusion reaction among banlanivimab-treated patients. As a result, we are advised that this treatment “may only be administered in settings in which health care providers have immediate access to medications to treat a severe infusion reaction, such as anaphylaxis.”
Practically, these gargantuan logistical hurdles may make the limited supply moot — all of us are trying to figure out how to deliver this promising treatment to prevent hospitalizations, and it’s not an easy nut to crack.
But already there’s a sense that these difficulties could exacerbate existing disparities in COVID-19 outcomes, with underserved populations missing out again on the benefits of this tricky treatment.
Let’s imagine a hospital or other healthcare delivery system sets up a program to administer banlanivimab to people diagnosed with COVID-19 as outpatients. Because of drug supply constraints and the duration of the infusion and monitoring time, they limit the number of treated patients to two per day (a morning and an afternoon session), which is to be administered in a specialized infusion site separate from immunocompromised patients.
Patients are referred by their primary clinicians, or they can call themselves. An intake nurse or other health professional speaks with them, reviews the relevant medical history, and ultimately determines whether they meet the “high-risk” criteria for treatment. If so, they schedule the patient for one of the two daily treatment slots.
Sounds simple, right?
Now let’s consider two imaginary (but quite plausible) patients newly diagnosed with COVID-19, both of whom would meet eligibility criteria for banlamivimab therapy.
The first is a 74-year-old semi-retired lawyer with hypertension and adult-onset diabetes. He could lose a few pounds, so tries to play tennis at his club in Wellesley as often as possible. He gets regular check-ups in the hospital system’s primary care network. Because of that network, he periodically receives health alerts through his hospital’s patient portal, including reminders to schedule his eye exams, blood tests, and immunizations.
The second imaginary patient is a 71-year-old woman from the Dominican Republic who moved to Boston five years ago to live with her daughter and grandchildren. Although she worked at a restaurant before she moved (gaining quite a few pounds with on-the-job snacking), she now finds the language barrier difficult here, so does not work. She mostly stays at home, sometimes socializing with other older people in her neighborhood who also speak Spanish. She receives some primary care at her local community health center; they have recommended that she start treatment for high blood pressure and diabetes, but the clinicians keep changing, and not all of them speak her language, so she never did.
Which patient is most likely to be referred for a banlanivimab infusion? Which one is more likely to call and advocate for themselves?
I suspect no one needs a medical degree to answer those questions.