Baystate Medical Center infectious disease chief considers antibody therapy part of ongoing ‘chess game’ with COVID-19
SPRINGFIELD – Although vaccinations have reduced the number of cases and deaths of COVID-19, antibodies made in the lab and administered to help the body’s immune system fight the coronavirus are playing a role during the pandemic.
Monoclonal antibody therapies were catapulted to the public last fall when President Donald Trump received one – REGEN-COV2 – after testing positive for COVID-19. New drugs based on monoclonal antibodies continue to receive emergency clearance from the United States Food and Drug Administration for use on COVID-19 positive individuals who have not been hospitalized but are at risk of serious infection.
Dr Armando Paez, head of infectious diseases at Baystate Medical Center, sees new potential for their use based on the results of clinical trials, particularly for REGEN-COV2. It assesses the success of their administration under current FDA clearance in the Baystate program.
“The promise is you avoid hospitalization and we still have to look at our data, but that’s what clinical trials suggest,” Paez said. “There are a lot of files to look at and we are looking at which ones were offered and which were infused and which ones were proposed and were eligible and refused to have it. We will see if there is a difference between the number of people admitted and those who were actually eligible and did not receive an infusion for some reason. “
In March, Regeneron declared phase 3 trial results for its REGEN-COV2 reduced the risk of hospitalization or death in high-risk out-patient patients with confirmed mild to moderate COVID-19 by 70% compared to placebo, and the drug was found to be effective against five major variants.
Paez said that “the chances of a person getting infected are very low now compared to last year when there was no vaccine, but the virus is still present in the community.”
It also remains a disease, the complications of which can be serious and fatal.
“The number of new COVID-19 cases will be the determining factor and this is affected by the vaccination rate and the increase in dominant variants,” Paez said of what in the future will impact the demand for treatment by monoclonal antibodies and whether licensed vaccines will continue to protect against all circulating variants and for how long. “If we stop transmission through vaccination, there will be no epidemic. The unvaccinated are the sitting ducks. Everyone is protected.
He says science supports the potential of monoclonal antibody therapies to reduce the risk of infection in an unvaccinated person exposed to the virus as well as in those who do not develop an immune response when vaccinated or infected, which is under investigation in REGEN-COV2 undergoing clinical trials.
“It’s like a game of chess and staying three steps ahead,” Paez said of the fight against the continuing pandemic virus. “It’s a wonderful story, but it’s a story written with a perspective that brings in a lot, including science and human behavior.”
In April, Regeneron reported that the results of a Phase 3 clinical trial in which REGEN-COV2 was administered subcutaneously, that is, by injection into the tissue under the skin, has been shown to reduce the risk of symptomatic infections by 81% in those who were not infected when they started the test.
The trial was conducted in conjunction with the National Institute of Allergy and Infectious Diseases to determine the effect of REGEN-COV on uninfected people without antibodies or any symptoms of COVID-19 who lived in the same household as a person tested positive for the virus within the four days before.
Results showed 72% protection against symptomatic infections in the first week, and 93% in the following weeks. It has also been reported that people treated with REGEN-COV who experienced a symptomatic infection resolved their symptoms within one week, compared to three weeks with placebo.
Regeneron said he plans to seek FDA Emergency Use Clearance administer REGEN-COV2 as a preventative treatment for COVID-19 in certain populations using a subcutaneous dose of 1200 mg.
Paez said the science behind infusing or injecting lab-made antibodies targeting a particular virus after exposure is that “it takes a few weeks to develop antibodies against a presentation antigen or vaccine and you are very. vulnerable, but if you passively infuse antibodies, you hope to neutralize the virus and help reduce the risk of the patient becoming ill. “
“There are several diseases for which we did this to neutralize the virus,” Paez said.
Earlier this month, Regeneron said the results of a Phase 3 clinical trial involving 9,785 patients in the UK called the RECOVERY trial showed that REGEN-COV reduce the risk of death 20% in patients hospitalized with COVID-19 who had not mounted their own immune response against the virus.
“The results of the RECOVERY the trial was not Peer reviewed and need more studies to find out if we can actually use REGEN-COV2 on hospital patients who had serious illness but no antibodies and could they benefit from it, ”said Paez. “FDA clearance at this time is not to use it in hospitalized patients or with progressing disease that requires supplementation with oxygen. This use is excluded for the moment, but maybe it will not be.
Paez said the Massachusetts Department of Public Health distributed licensed monoclonal antibody therapies to designated infusion centers late last year. Baystate’s is now based in Noble on its Westfield campus and one of only two in western Massachusetts with requirements to ensure equal access for all populations.
Baystate’s program delivered therapy to 321 people out of 597 referrals made to date both inside and outside its network, and said the majority had received REGEN-COV2, a- he declared.
The results of clinical trials of the drug have led to updates at its origin emergency use authorization. It consists of the antibodies casirivimab with imdevimab which target the spike protein of the pandemic virus and prevent it from attaching to and entering cells in the human body.
Trump received it in October, before it was cleared, along with other drugs as part of his COVID-19 treatment. He called it a “cure”, creating a leap in the participants interested in participating in clinical trials as well as in the course of action of the manufacturer Regeneron who immediately applied for and obtained emergency use authorization.
The federal government, which helped fund the drug’s development, purchased more than a million doses for distribution to states.
Other COVID-19 monoclonal antibody treatment therapies with FDA clearance for such emergency use include Eli Lilly’s bamlanivimab with etesevimab and GlaxoSmithKline sotrovimab which received this authorization at the end of May.
Lilly’s bamlanivimab was the first to receive emergency clearance in the fall, followed closely by REGEN-COV2, at a time when there were few promising therapies for COVID-19.
The FDA has since revoked bamlanivimab authorized use in itself due to the increase in viral variants which he says are “resistant to bamlanivimab alone, leading to an increased risk of treatment failure”. Federal distribution of bamlanivimab with etesevimab has been suspended in several states, including Massachusetts, where the percentage of Brazilian and South African variants believed resistant to this drug cocktail would exceed 10 percent.
The FDA recently extended authorization for REGEN-COV2 to be given at a lower dose and in a shorter infusion time, 20 minutes instead of over an hour, and to be given by injection when this avoids delay in an eligible patient who receives it.
Paez said Baystate’s COVID-19 monoclonal antibody program has had a total of 597 referrals to date with 144 of 321 treatments given receiving REGEN-COV.
“We started our program here in Baystate with the first patient in December and first used what was available at the time, which is the bamlanivimab which was cleared in early November, then we started using the suit REGEN-COV2 it was the second monoclonal antibody treatment that was cleared a few weeks later, ”Paez said. “We decided to switch to the combined cocktail even before there was any discussion on the variants”
He added that in February, when “Eli Lily proposed a shorter infusion time and a lower dose with his licensed combination cocktail, bamlanivimab with etesevimab, we switched to that combination.”
“However, more recently due to some variants, notably the P.1 (Gamma) variant from Brazil which circulates at more than 10% in certain states, including initially in Massachusetts, the FDA advised bamlanivimab / etesvimab should not be used in these states, Paez said. “We have come back to REGEN-COV2”.
Paez said that among the patients Baystate had infused so far with monoclonal antibody therapies “there have been very few potentially related side effects” and none serious with most in the form of chills and fever.
He said referrals to the program were low in recent weeks as the number of vaccinations increased, although at least one referral received an injection rather than an infused dose of REGEN-COV2 under his recent clearance. enlarged.
“Operationally, I am proud to say that we have been able to come up with a plan to deliver monoclonal antibody therapy to our population, as Hampden County in particular has been one of the highest risk. positive cases, ”Paez said.
He noted molnupiravir, an as yet unauthorized antiviral drug that Merck is developing in collaboration with Ridgeback Biotherapeutics, “may displace monoclonal antibodies” into their current licensed use. The drug is intended for outpatients with lab-confirmed COVID-19 and at least one risk factor associated with poor disease outcomes.
“It is an oral agent in a promising phase 3 trial, the MOVe-OUT study, and which could displace monoclonal antibodies,” Paez said. “He might be ready for fall. It’s a big deal.
In the meantime, Paez said Baystate’s monoclonal antibody therapy program “is still open and ready to respond to those who are eligible.”
“We are here and we will monitor the advancement of science and adapt to the call to action to fight this pandemic and this infection,” said Paez who was appointed chief infectious disease officer less than a year ago. before the pandemic started in late 2019. “It has been nerve-racking, but thank goodness we know more now than we did at the beginning. “