A study in New England Journal of Medicine (NEJMThis week showed that treatment with a plasma-derived virus-neutralizing monoclonal antibody (LY-CoV555) by Eli Lilly reduced viral load, decreased severity of symptoms, and absent Any serious side effects in outpatients.
Data from the phase 2 trial confirmed preliminary September results from a smaller group of outpatients – those who came to the clinic – had similar results.
Animal studies of neutralizing antibodies have shown promising results, with significant reductions in viral load in the upper and lower respiratory tract, where SARS-CoV-2, the virus that causes COVID -19, is thought to bind and cause disease. Neutralizing antibodies such as LY-CoV555 bind to the mutant protein of SARS-CoV-2 to prevent the virus from attaching and penetrating the cells of the upper and lower respiratory tract.
The SARS-CoV-2 neutralization antibody (BLAZE-1) Viral Blocking and Infiltration Test has used different doses of LY-CoV555 for outpatients with mild COVID-19 or has just been diagnosed recently. The trial is part of ongoing research with multiple treatment groups that will eventually attract more than 800 participants.
From June 17 to August 21, researchers randomly assigned 452 COVID-19-positive patients with mild or moderate symptoms at 41 US sites to the groups that were infused. Single 1 hour circuit with one of three doses of LY-CoV555 (700-, 2,800- and 7,000 milligrams [mg]; 309 patients) or placebo (143 patients). Patients were assessed for viral load after infusion on day 11 and clinical results such as hospitalization, emergency examination, or death until day 29, and safety of treatment.
Reduce the viral load, the severity of symptoms
Study authors found a significant reduction in viral load in patients receiving a dose of 2,800 mg, a factor of 3.4 lower than baseline (-0.53, 95% confidence interval. [CI], -0.98 to -0.08; P = 0.02). Patients taking doses of 700 and 7,000 mg also experienced a milder decrease.
Patients receiving any dose of LY-CoV555 had a lower symptom severity (graded from “0” for asymptomatic to “3” for severe symptoms) on day 2 by day 6 compared with the placebo group. The change from baseline symptom scores continued better in the treatment groups than in the placebo group until day 11 and a similar safety profile for both groups.
COVID-19-related hospitalization or emergency room visits were 1.6% (5 out of 309 patients) in the antibody group and 6.3% (9 out of 143 patients) in the placebo group, shows an association between higher viral clearance and lower hospitalization rates. Hospitalization rates were higher in patients 65 years of age and older with a body mass index of 35 or more— 4% and 15% for the antibody and placebo groups, respectively.
Neither patient in the LY-CoV555 group had serious adverse effects, compared with one patient in the placebo group. The percentage of all adverse events was similar: 22.3% for the treatment group and 24.5% for the placebo group.
These data indicate that the treatment is safe, the study authors conclude. “Patients given LY-CoV555 had fewer hospitalizations and a lower symptom burden than those given a placebo, with the most pronounced effect observed in the cohort at risk. If this result is confirmed in additional analyzes in this trial, LY-CoV555 could become a useful treatment for emergency use in patients with Covid-19 disease. recent diagnosis. “
Trial suspension for hospital patients
Interim analysis came 1 day after the National Institutes of Health canceled the LY-CoV555 clinical trial of 326 hospitalized patients, suggesting that it is unlikely to improve outcomes in this group of patients.
The suspension of study enrollment was triggered by the Data and Safety Supervision Board (DSMB) on October 13 when the pre-set safety boundary was crossed showing differences in the clinical status of the admitted patient. in the treatment group and in the placebo group. Finally, no significant safety concerns have been identified, and the DSMB’s recommendation to suspend the trial this week stems from the lack of clinical benefit for hospitalized patients.
Scientists Eli Lilly suspect that hospitalized patients – as opposed to outpatients – may show a lack of clinical benefit from LY-CoV555 because of longer infection, more severe symptoms. and receive treatment differently from non-hospitalized patients.
“For these reasons, hospitalized patients may be less likely to benefit from neutralizing antibodies, which are an addition to the patient’s own immune system, as they may have developed an antibody response. Its own endogenous form and in the course of the disease are characterized by an inflammatory response to the virus, “the company wrote in an October 14 newsletter.
Potential early intervention
Researchers Eli Lilly are confident that LY-CoV555 can prevent disease progression in patients with pre-stage COVID-19. Phase 2 outpatient studies and planned phase 3 studies focusing on antibody treatment in residents and staff of long-term care facilities continue to be conducted.
Peter Chen, MD, of Cedars-Sinai in Los Angeles and the first author of the NEJM study, said: “It is important to treat people with COVID-19 as soon as possible after diagnosis to prevent blocking the development of more severe disease ”. an Eli Lilly press release this week. “Our findings indicate that neutralizing antibodies may be potentially useful in this early stage intervention,” he added.