IDStewardship

5 Things To Know About Bamlanivimab

In this article an infectious diseases pharmacist identifies five things to know about bamlanivimab. 

Authored By: Timothy P. Gauthier, Pharm.D., BCPS, BCIDP

Disclaimer: Information on this topic is emerging rapidly, which could render some or all of this content inaccurate. Take note of when this page was last updated and visit www.bamlanivimab.com for the most update info. 

16 April 2021 – Important Note

Today the FDA revoked the EUA for bamlanivimab monotherapy. The EUA for bamlanivimab-etesivimab remains standing.

29 March 2021 – Important Note

 Bamlanivimab is not active against numerous circulating variants and has dropped out of favor. Details on this are provided in the Fact Sheet for Healthcare Providers.

New section –  posted 13 February 2021 (updated 9 March 2021)

FDA has released an EUA for bamlanivimab + etesevimab. It is expected bamlanivimab + etesevimab will replace use of bamlanivimab alone.

The FDA EUA qualifying criteria for the combination product are the same as for bamlanivimab alone and bamlanivimab monotherapy remains under EUA. The NIH and IDSA COVID-19 Guidelines give stronger recommendations to bamlanvimab-etesevimab than either bamlanivimab monotherapy or the Regeneron product casirivimab-imdevimab. Bamlanivimab-etesevimab may be more effective versus variants than bamlanivimab alone.

Notes on the topic:

Important note: Timing between antibody therapy and COVID-19 vaccination is addressed by CDC here.

Bamlanivimab Original Post Content

Last updated: 1 December 2020

Originally posted: 14 November 2020

Bamlanivimab (LY-CoV555) is a neutralizing IgG1 monoclonal antibody manufactured by Eli Lilly that works against the SARS-CoV-2 spike protein to reduce viral replication. An FDA Emergency Use Authorization (EUA) for bamlanivimab was released on 9 November 2020. Bamlanivimab is not currently FDA-approved for any indication.

Bamlanivimab is very difficult to pronounce. Even Jimmy Fallon got in on the fun of trying to say it, which happens to start to sound like the Ram Jam song Black Betty the more you say it. So where does it get its name from? Well, for the sceintific name “LY” indicates the molecule belongs to Eli Lilly and CoV555 indicates it is one of their potential COVID-19 treatments. Generic drug name bamlanivimab breaks down into “bamlan” (a two-syllable non-specific stem prefix meeting generic name requirements), “vi” (denotes it’s targeting a virus), and “mab” (monoclonal antibody). You can read all about naming monoclonal antibodies here, it’s actually pretty neat. I thought the first “i” in “bamlani” indicated the animal species it was derived from (human plasma in this case), but I can’t find anything to confirm it so have to leave that part open for now.

With a new EUA coming out amidst a pandemic you can imagine there is a lot of interest in what positive impact this therapy could possibly have on public health, particularly as COVID-19 cases trend upwards and persist at an alarming rate in the United States.

With the intent of helping pharmacists and other healthcare professionals gain a deeper understanding of the topic, the following five things to know about bamlanivimab are provided…

1. Bamlanivimab is only authorized for patients who meet specific criteria 

Importantly, when considering the criteria to use bamlanivimab take note that it may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation. So one of the messages is give it early or don’t give it at all.

Details on which patients can get bamlanivimab are provided below, but in short it has to be a patient who:

  1. Has a positive direct SARS-CoV-2 test, PLUS
  2. Is not sick enough to require hospitalization, PLUS
  3. Is not sick enough to require oxygen therapy, PLUS
  4. Is at high risk for progressing to severe COVID-19 and/or hospitalization, PLUS
  5. Is within 10 days of symptom onset

The EUA indicates bamlanivimab “is authorized for treatment of mild to moderate COVID-19 in adults and pediatric patients with positive results of direct SARS-CoV-2 viral testing who are 12 years of age and older weighing at least 40kg, and who are at high risk for progressing to severe COVID-19 and/or hospitalization.” The Fact Sheet For Prescribers indicates that it must be given within 10 days of symptom onset. 

The EUA explicitly states that bamlanivimab is not authorized for use in patients: 

  • Who are hospitalized due to COVID-19, or
  • Who require oxygen therapy due to COVID-19, or
  • Who require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity

The EUA describes people at high risk for progressing to severe COVID-19 and/or hospitalization as patients who meet at least one of the following criteria:

  • Have a body mass index (BMI) ≥35
  • Have chronic kidney disease
  • Have diabetes
  • Have immunosuppressive disease
  • Are currently receiving immunosuppressive treatment
  • Are ≥65 years of age
  • Are ≥55 years of age AND have
    • cardiovascular disease, or
    • hypertension, or
    • chronic obstructive pulmonary disease/other chronic respiratory disease.
  • Are 12 – 17 years of age AND have
    • BMI ≥85th percentile for their age and gender based on CDC growth charts, or
    • sickle cell disease, or
    • congenital or acquired heart disease, or
    • neurodevelopmental disorders, for example, cerebral palsy, or
    • a medical-related technological dependence, for example, tracheostomy, gastrostomy, or
    • positive pressure ventilation (not related to COVID-19), or
    • asthma, reactive airway or other chronic respiratory disease that requires daily medication for control

That’s a lot of criteria, right!?! …As you can see the criteria for who can get bamlanivimab are strict in regards to the illness, but broad in regards to the percentage of the overall population who is at risk for progressing to severe COVID-19 and/or hospitalization.

2. Bamlanivimab may help prevent high risk patients from progressing to requiring hospitalization

The BLAZE-1 trial investigated 3 different doses of bamlanivimab versus placebo in outpatients with recently diagnosed mild or moderate COVID-19. The primary endpoint was change from baseline in the viral load at day 11. An interim analysis of the data did not indicate a difference between the intervention drug versus placebo for this primary outcome. However, one of the secondary outcomes did show promise.

The Fact Sheet For Healthcare Providers reports that in the intervention group 2% (5 of 309) progressed to COVID-19-related hospitalization or emergency room visits compared to 6% (9 of 156) in the placebo group. Drilling down within the same endpoint to subjects at higher risk for hospitalization, the intervention group had 3% (4 of 136) progress to COVID-19-related hospitalization or emergency room visits compared to 10% (7 of 69) in the placebo-treated subjects.

This means that not only might bamlanivimab use improve patient outcomes, it also has the potential to reduce the burden of COVID-19 on stressed hospital systems.

Hat-tip to Dr. Drekonja for also pointing out the number needed to treat (NNT) here as an important thing to consider. For the overall secondary endpoint noted, the NNT is 22, then drilling down to those at “higher risk” the NNT is 14.

Added 30 January 2021: Some people are calling the data on bamlanivimab into question. Here is one perspective on it.

3. The logistics of bamlanivimab use are considerable

The window of opportunity is just 10 days from symptom onset. Patients need to have a positive direct SARS-CoV-2 test which may not be readily available or have a fast turnaround time depending upon local supply and demand. Treatment with bamlanivimab means sending a known COVID-19 patient into the healthcare environment bringing risk for exposures and need for infection control measures. Healthcare settings already equipped to provide infusions of medications such as this likely have existing at-risk clientele that need to be protected from potential SARS-CoV-2 infection. Each bamlanivimab patient requires an approximate minimum of 3 hours on site between administration of the medication (1 hour), post-administration observation period (1 hour), and other intake/release activities. 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).

The list of challenges goes on. In time these challenges will be overcome, but in the meantime, healthcare systems across the country will be struggling to manage patients safely, effectively, and efficiently.

4. Bamlanivimab can cause serious toxicity

In clinical trials with bamlanivimab there was one patient who had an anaphylactic reaction and one patient who had a serious infusion-related reaction. In both cases the infusions were stopped and treatment was required. One of the patients required epinephrine. Both events resolved. While it may not be common, these are significant potential adverse drug reactions to beware and locations providing this therapy need to be equipped to manage these should they occur.

Infusion-related reactions can include fever, chills, nausea, headache, bronchospasm, hypotension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, and dizziness.

Bamlanivimab is otherwise generally well tolerated as compared to placebo.

5. The supply and demand of bamlanivimab is sure to be a roller coaster

The Federal Government has purchased 300,000 doses of bamlanivimab from Eli Lilly, which should be available over the next two months (from mid-November 2020 to mid-January 2021). This first week of the EUA, there are 79,350 vials  being allocated across the United States. Each vial is one 700 mg dose. Allocation is facilitated from the Federal Government to State Health Departments and subsequently to hospitals and healthcare systems, with product distribution coming from AmerisourceBergen.

You can track the weekly allotments by state here.

Given this is a new product with logistical challenges, it will be interesting to witness the dance between an adequate supply of medication and an adequate supply of beds/chairs in which to infuse the medication (along with staff to administer the infusions and monitor patients).

For now bamlanivimab is free, but like remdesivir it is likely to transition to being fairly costly. How much bamlanivimab will cost remains a mystery at this time. There are also many questions about reimbursement that are unknown at this time.

Final Thoughts

The complexities of bamlanivimab go well beyond this article and there is no doubt we will learn much about this therapy in the coming weeks. Like many in my field, I will be closely watching #IDtwitter and the literature on this topic. I hope you have found this helpful and encourage you to explore the resources below to learn more about bamlanivimab (which I still have a hard time pronouncing!!).

If there is a resource that is not listed or something can be made more accurate, let me know here!

Bonus point for fun: If you take the chorus to the “Cupid Shuffle” song, the syllables in bamlanivimab line up perfectly… some would even argue it is a better song fit than Ram Jam’s Black Betty!

BAMLANIVIMAB RESOURCES

DISLAIMER: The views and opinions expressed in this article are that of the author and do not necearilly reflect those of any past, current, or potential future employer.

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