Monoclonal Antibody Shows Promise in Reducing COVID-19 Severity
A novel monoclonal antibody is showing promise in keeping COVID-19 patients from developing severe symptoms that lead to emergency care or hospitalization. Interim results were positive in outpatients receiving the therapy compared to those who did not. Here is more information.
LOS ANGELES – One of the challenges in treating patients with COVID-19 is keeping them from developing severe symptoms requiring emergency medical care or hospitalization.
Interim results from a new study published in The New England Journal of Medicine suggests a novel antibody could be promising therapy to achieve that
The multisite, Phase II clinical trial tested three different doses of LY-CoV555, a monoclonal antibody derived from the blood of a recovered COVID-19 patient. The trial continues, but the interim analysis indicates a reduced viral load in outpatients with mild to moderate cases of COVID-19 at the 2,800-milligram dosage level compared to those with usual care. Cedars-Sinai-led researchers point out that the group receiving the treatment also had reduced rates of hospitalization and emergency medical care among patients at all dosage levels.
"For me, the most significant finding was the reduction in hospitalizations," explained lead author Peter Chen, MD, professor of Medicine and director of the Division of Pulmonary and Critical Care Medicine at Cedars-Sinai. "Monoclonal antibodies like this have the potential to reduce the severity of COVID-19 for many patients, allowing more people to recover at home."
Background in the report explains that monoclonal antibodies attach themselves to a virus and preventing it from replicating. In this case, according to the industry-funded study, LY-CoV555 binds to a spike protein required by SARS-CoV-2 to enter human cells and replicate. The slow down in replication give the patient’s immune system to get ahead of the curve and fight the virus.
"What we're doing is preventing the virus from causing too much damage early on in the process," Chen said. "We're buying the patients time, so that their bodies can start developing their own immunity to fight the virus."
Intravenous doses of either 700, 2,800 or 7,000 milligrams of the antibody, or a placebo, were provided to participants in the randomized, double-blind study . Nasopharyngeal swabs were used to test patients' viral load before administering the antibody and again at several points after treatment was received, and patients also filled out questionnaires about their subsequent symptoms and treatment.
Researchers randomly assigned 452 patients to receive a single intravenous infusion of neutralizing antibody LY-CoV555 in one of three doses (700 mg, 2800 mg, or 7000 mg) or placebo and evaluated the quantitative virologic end points and clinical outcomes. Defined as the primary outcome was the change from baseline in the viral load at day 11.
The interim analysis notes that, in September, the observed mean decrease from baseline in the log viral load for the entire population was −3.81, for an elimination of more than 99.97% of viral RNA. The authors report that, for patients who received the 2800-mg dose of LY-CoV555, the difference from placebo in the decrease from baseline was −0.53 (95% confidence interval [CI], −0.98 to −0.08; P=0.02), for a viral load that was lower by a factor of 3.4. They say they observed smaller differences from placebo in the change from baseline among the patients who received the 700-mg dose (−0.20; 95% CI, −0.66 to 0.25; P=0.38) or the 7000-mg dose (0.09; 95% CI, −0.37 to 0.55; P=0.70).
Results indicate that, on days 2 to 6, the patients who received LY-CoV555 had a slightly lower severity of symptoms than those who received placebo. At the same time, the percentage of patients who had a Covid-19–related hospitalization or visit to an emergency department was 1.6% in the LY-CoV555 group and 6.3% in the placebo group.
“In this interim analysis of a phase 2 trial, one of three doses of neutralizing antibody LY-CoV555 appeared to accelerate the natural decline in viral load over time, whereas the other doses had not by day 11,” researchers conclude.
Further studies will be needed to validate these results, according to the investigators.
"The publication of these data in a peer-reviewed journal adds to the growing body of evidence for the potential utility for neutralizing antibodies as therapeutics for people recently diagnosed with mild to moderate COVID-19, particularly high-risk patients," said Ajay Nirula, MD, PhD, vice president of immunology at Eli Lilly and Company and co-first author of the study. "These data show LY-CoV555 may be effective in treating COVID-19 by reducing viral load, symptoms and the risk of hospitalization in outpatients."
The study adds that the reduction in hospitalizations was seen across all demographic groups, including those in high-risk categories: adults older than 65 and those with a high body mass index (greater than 35). For high-risk patients, hospitalization rates were 4.2% in patients treated with the antibody, compared with 14.6% in placebo-treated patients. The safety profile of patients treated with LY-CoV555 was similar to that of placebo-treated patients.
"We know that COVID-19 is especially hard on the elderly, the obese and people with certain pre-existing health conditions," Chen said. "Antibody treatments like this may have the most benefits for people in these higher-risk categories."