The medical and research establishments certainly have given their best during this pandemic. Eli Lilly is no exception, having marshalled thousands of scientists, research professionals, and clinical trial teams to develop and test novel drugs with the aim of treating a totally new and deadly virus. Recently, one of company’s breakthrough investigational monoclonal antibody therapies, first known as LY-CoV555 and now “Bamlanivimab,” was made available as a COVID-19 treatment under an Emergency Use Authorization (EUA), per the NEJM’s Journal Watch Blog. The only acceptable use at this time involves outpatients currently deemed a high risk for severe disease progression and/or hospitalization. Much like remdesivir, the first approved therapy—controversially many may add—this emergency use treatment fails the ease-of-administration test. In the case of Bamlanivimab, it’s not only difficult to pronounce the investigational product’s name, but also even more challenging to actually administer it to patients. The federal government has paid Lilly $3.75 billion for investigational product costs (deal done at $12,500 per treatment, for 300,000 in initial shipment) on the taxpayers’ “dime.”
Also, it is more than likely that this is just a fraction of the actual cost, when considering the complexity and impracticality of administering the product. The provider price tag for the myriad of services, resources, and associated efforts will be substantial. Moreover, although well intentioned, the EUA and associated problems of delivery will likely only serve to intensify health inequities during the COVID-19 pandemic. In the Journal Watch piece, Dr. Paul Sax takes a critical look at the challenges of delivering this investigational product in pandemic conditions. And considering that the approved use of remdesivir didn’t allow for easy outpatient administration either, one has wonder why this chasm builds between what is researched and approved (if just on an emergency basis) and the true needs of the healthcare market at this point in time.
So, the federal government spent $3.75 billion for the first 300,000 doses of the investigational product, but that’s just a start. In the deal with Lilly there is an option to buy plenty more product at the same price point. The premise was that it will be free for the patient, but let’s look at what it actually takes to administer this experimental drug. According to Dr. Sax, who is Clinical Director, Infectious Disease Clinic and Professor of Medicine, Harvard Medical School, the actual complexity and obstacles associated with the implementation of this treatment raise many questions for the research establishment. But why is it so difficult for a patient to “take” Bamlanivimab? TrialSite summarizes those issues here:
- Limited supply. This is perhaps to be expected with an advanced, novel life-science-based therapy approved on an emergency basis. Although Lilly has declared they are ramping up manufacturing in the short run, by some estimates the current supply could be exhausted within a couple of weeks.
- Requires intravenous use. Many clinicians don’t have the ability to offer fast, affordable infusions in clinic.
- Bamlanivimab must be administered within 10 days of symptom onset. A growing number of physicians want to treat patients immediately. Hence, protocols are hotly debated in the physician (clinic) community. And a full ten days may be too late, regardless, Sax notes that the, “precise window of opportunity” for treatment isn’t known. What is becoming clearer is that the Lilly and Regeneron monoclonal antibody treatments don’t seem to have great potential for hospitalized patients with COVID-19.
- Patients are actually most contagious between 1 day before and 5 days after onset of COVID-19 symptoms—this is when most secondary transmissions occur. It’s at this time that patients should be brought in for treatment according to Sax.
- Unfortunately, a majority of infusion centers have a high proportion of immunocompromised patients. That is, individuals facing rheumatological, GI, and neurology conditions who are receiving intravenous immunosuppressive treatments; in addition to cancer patients receiving chemotherapy, etc. Is it easy or straightforward to bring highly contagious COVID-19 patients in large numbers to these facilities? Remember, it’s primarily these facilities that would be available.
- A good number of infusion centers are not optimized for urgent referrals.
- The infusion process is timely and complex and will undoubtedly be costly. As was cautioned already by some in the health sector, the costs will be significant including the set-up and post-treatment monitoring. This isn’t a procedure akin to a quick injection. Hence the positioning of the therapy, subsidized by the government, doesn’t account for all the provider (and staff) time and effort.
- Emergency departments won’t desire a 3-hour treatment, clogging mission-critical patient flow.
- The Bamlanivimab formulation is, “tricky to prepare and not stable for very long.”
- Serious side effects are possible. Importantly, these side effects failed to materialize in a recent published paper, but they are noted in the package insert.
Sax reminds us that the federal government and logistical elements associated with Operation Warp Speed, combined with the onerous path to investigational product delivery to the patient in this case, raises the specter of how to efficiently and effectively take care of the patient with COVID-19 with this promising drug: “not an easy nut to crack,” Dr. Sax emphasizes.
Health Equity Concerns
Sax also notes that the realities of economic, racial, and other chasms involved with the social determinants of health rear their ugly head in this modern pandemic. Based on the way health care during the COVID-19 pandemic has already unfolded, underserved populations will more than likely miss out on any benefits associated with this promising yet difficult-to-administer treatment. Follow the link above to review the real-world-like scenarios the doctor proposes in order to forecast why the already privileged will benefit from this EUA over those most at risk—the very people an EUA should target.