The first monoclonal antibody drug Bamlanivimab was given a EUA or emergency use authorization by the US FDA last two weeks ago ( November 9, 2020 ) to treat direct SARS-CoV-2 or CoViD19 positive patients with mild to moderate signs and symptoms of the disease. The new antibody treatment was also given to the US President Donald Trump during his confinement in the army hospital when he contracted the novel disease a few weeks before the scheduled US election and recovered fast, then was subsequently discharged early in very much improved condition and in the surprised of the American public and of the whole world.
Antibodies in letter Y morphological shape ” attacking ” by binding to the spike proteins of the SARS-CoV-2 virus.
It has been nearly eleven months had passed that CoViD19 disease had no known definite treatment and many rich countries all over the world together with several big pharmaceutical companies and research scientists are in the race against time in discovering and developing drug/drugs for the novel disease that infects millions ( 58,112,434 cases ) and killed millions ( 1,380,980 cases ) of people worldwide as of today. World leaders from powerful countries such as the United States President Donald Trump announced and promised the availability of vaccines before the US elections but it never materializes. The United States of America has now a new president and still, no vaccines are available for the public.
There are several repurposed drugs that were given emergency use authorization or EUA a few months ago for the treatment of CoViD19 such as convalescent plasma, dexamethasone, remdesivir, and recently Bamlanivimab an investigational drug and a monoclonal antibody which is artificially engineered and manufactured by Elli Lilly was given a EUA or Emergency Use Authorization by the US-FDA for the treatment of CoViD19 patients as a form of a bridge therapy while waiting for an available definite drug treatment or vaccine treatment for the novel pandemic.
What is meant by Emergency Use Authorization?
It is an act issued or given by the US-FDA to a certain medicine or product authorizing it to be used in an emergency situation for the treatment of certain diseases such as the novel pandemic where there is no known definite or potential treatment can be found or given. One of the characteristics of the candidate drug or treatment to be given EUA must have its potential effect or benefit outweighs the potential risk or side effect when given to patients with the disease.
What is Bamlanivimab?
It is a form of a molecular protein artificially engineered and develop in the laboratory that function as an IgG1 neutralizing monoclonal antibody that will stop viral replication of SARS-CoV-2 by binding to the receptor-binding domain ( RBD ) of the spike protein of the virus thus preventing attachment to the ACE2 receptors and subsequently block entry into the human cells and play the same function as a host natural or innate antibody thus resulted in a mechanism called passive immunity.
Bamlanivimab is also known as Ly-CoV555 as mentioned in the BLAZE-1 trial which resulted to decrease hospitalization or hospital emergency department visits when given to patients with mild to moderate CoViD19 positive patients and the three doses of the drug showed no serious adverse events or side effects when administered to the same subsets of patients. The drug is available in a 700mg/20ml intravenous infusion vial preparation and is given in infusion intravenous route for the one-hour duration to the patient/s. The drug is manufactured by Eli Lilly and is newly approved by US-FDA for emergency use authorization therapy for CoViD19 patients with mild to moderate symptoms.
Criteria for patient/s to be given with Bamlanivimab:
The drug is given to ambulatory direct SARS-CoV-2 ( RT-PCR and Antigen Tests ) positive patients who are 12 years old and above who weigh more than or equal to 40kgs. with less than 10 days of mild to moderate CoViD19 signs and symptoms onset. The drug is also given to patients that don’t require oxygen therapy and hospital admissions but are at high risk for the disease to develop or progress to severe disease due to multiple comorbidities or risk factors. It is very important to note as mentioned that the drug must be given to patients with symptoms of less than ten days in order for the drug to be effective. The drug Bamlanivimab should not be given as prevention therapy for CoViD19 disease nor it is recommended for the treatment of CoViD19 patients that needs hospitalization ( ACTIV-3 Clinical Trial ).
How is bamlanivimab given to the patient/s:
Bamlanivimab preparation is in a 700mg/20ml vial and once diluted, it must be used or given to the patient/s within 7 hours if allowed to stay at room temperature. And then if the vial that contains the drug is opened and then diluted and refrigerated, it must be used within 24 hours period but before giving the drug to the patient, the drug should stay outside the storage container for a minimum of 20 minutes to achieve equilibration at room temperature. And Bamlanivimab must be not be exposed to direct sunlight until the time of its use. The drug is given at 700mg in 200ml normal saline solution via intravenous infusion route for a one-hour duration and the patient/s must have initial baseline vital signs prior to the administration of the drug.
During the ongoing intravenous infusion administration of Bamlanivimab, the patient must be closely monitored for any occurrence of adverse or serious drug reactions. Then after giving the drug, the patient must stay for another 1 to 2 hours in the hospital or clinic facility for further close observation or monitoring of an anaphylactic or adverse drug reaction post intravenous infusion administration of Bamlanivimab before sending the patient home or discharge from the health-care facility. The novel monoclonal antibody treatment must be given as a single dose therapy ( BLAZE-1 ) for CoViD19 patient/s with mild to moderate signs and symptoms. The unopened vial that contains Bamlanivimab is stored at 2 to 8 degrees Celsius ( 36 to 46 degrees F ).
Very common side effects of Bamlanivimab:
According to the BLAZE-1 clinical trial ( An interventional, randomized, double-blind, placebo-controlled trial ) results of the drug and the drug’s maker Eli Lilly, the most common side effects are gastrointestinal reactions such as nausea, vomiting, and diarrhea, few patients noticed dizziness and headache with skin itchiness and pain in the infusion site. These side effects happened in 2-4% of the patients. Less common infusion-related side effects are fever, chills, throat irritation, rashes, urticaria, myalgia, flushing, facial swelling, bronchospasm, and hypotension. The giving of antihistamine drugs will usually control the side effects of the drug Bamlanivimab. An ongoing clinical trial of Bamlanivimab is taking place as of the present time with regards to its further clinical safety profile. Likewise, Bamlanivimab is not excreted in the kidneys and not metabolized in the liver therefore there are no dose adjustments in patients with liver and kidney disease or problems.
There are several artificially engineered monoclonal antibody that is now being developed by big pharmaceutical industries all over the world especially in the United States but only Bamlanivimab as the first artificially engineered monoclonal antibody ( mab ) which was approved by the US-FDA for Emergency Use Authorization ( EUA ) in the treatment of ambulatory CoViD19 patients with mild to moderate symptoms. The drug is the first of its kind as a form of the therapeutic strategy developed by the drug maker Eli Lilly. The US federal government provided the gradual free distribution of the 300,000 vials preparation of the drug from Eli Lilly as of the present time and the American public is not so sure if it will be available for free in the succeeding months to come. I hope that the said drug will not be as costly compared to the antiviral drug remdesivir, but for sure its cost will be more than the intravenous drug remdesivir. And the drug’s production is limited. As mentioned that the said drug’s clinical efficacy and safety profile trial is still in progress as of the very moment and it is very important to continue monitoring the progress of the BLAZE-1 TRIAL at ClinicalTrials.gov since the drug is now been approved for emergency use in the treatment of CoViD19 patients with mild to moderate symptoms in the out-patient context.
On November 21, 2020, another artificially engineered monoclonal antibody combination from Regeneron Pharmaceuticals Inc. was also granted an Emergency Use Authorization or EUA by the US-FDA. Casirivimab and imdevimab are new monoclonal antibodies given to US President Donald Trump when he was admitted at the Walter Reed Army Hospital and contributed to the fast recovery of the US president. The two new monoclonal antibodies are given simultaneously together by intravenous infusion route and with almost the same precautionary administration measures applied to Bamlanivimab. The infusion side effects are almost the same with Bamlanivimab. It is also distributed by the federal government for free of charge. And the criteria for the patient’s eligibility to avail the said laboratory-designed monoclonal antibodies are also the same as Bamlanivimab.
State of the art and cutting edge technology mRNA vaccine are on the way and will be available in the near future, it is promising, safe, effective, and a game-changing ” disruptive technology ” not only in the field of cancer immunotherapy but also in the realm of the prophylactic and therapeutic applications versus infectious diseases. The problem encountered by the manufacturer with the mRNA vaccine is its ultra temperature cold chain storage. The very low or ultra temperature ( -50 to -70 degrees celsius ) remains a hindrance for the vaccine’s distribution to a population living in a warm climate, desert/arid regions or environment, and far distant remote location. But I think there are strategies that can be designed and develop by big, rich pharmaceutical companies to overcome such obstacles in vaccine transport and distribution in the very near future.
NEW UPDATE of Blaze-2 Trial: A Study of LY3819253 ( LY-CoV555 ) and LY3832479 ( LY-CoVO16) in Preventing SARS-CoV-2 Infection and COVID19 in Nursing Home Residents and Staff.
As almost everybody in the vaccine development industry knew the BLAZE-1 trial using intravenous bamlanivimab in treating mild to moderate CoViD19 patients with successful results during the previous months of the novel pandemic in 2020. And new vaccines are on the way are being made and develop for the novel disease, many old patients with chronic diseases in the nursing homes or residences together with the staff was infected and died of CoViD19. So to address the problem of this group of people, a pharmaceutical company Eli Lilly in collaboration with the US-National Institute of Allergy And Infectious Diseases ( NIAID), Abcellera Biologics Inc., and Shanghai Junshi BioscienceCo. Ltd. designed a clinical trial, BLAZE-2 in order to evaluate the drug LY-C0v555 or Bamlanivimab and LY3832479 or etesevimab in preventing SARS-CoV-2 infection in nursing home residents and staff.
BLAZE-2 is a Phase 3 Randomized Double-Blinded, Placebo-Controlled Prevention Trial. And almost 2000 long-term care facilities had participated in the study across many states in the United States Of America. The study enrolled 965 participants with 8 weeks follow-up and the result was announced last January 2021 with a good safety profile and low adverse event observed. It also lowered or reduced the risk of getting or contracting SARS-CoV-2 infection by 80 percent and it prevented symptomatically CoViD19 patients or residents to become or worsening to severe or critical CoviD.
Bamlanivimab and etesevimab are all recombinant neutralizing monoclonal antibodies that act against the spike protein of the SARS-CoV-2 virus, thus it prevents the virus from sticking to the ACE2 of the host cells and thereby blocks cellular viral entry. The combination treatment regimen of these two novel neutralizing monoclonal antibodies is a good strategy for the treatment of CoViD19 patients infected by the new highly potent transmissible variants of SARS-CoV-2 that is now circulating around the globe which infects people with increasing severity.
Laertes B. Amihan MD