Immunocompromised individuals, particularly those with B-cell deficiencies or who are currently taking immunosuppressive medications, are not capable of developing an adequate immune response to coronavirus disease 2019 (COVID-19) vaccination. This makes such individuals, who constitute close to 3% of the United States population, more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the development of severe COVID-19.
Previous studies have shown that a single dose of REGENCOV®, which is a combination drug consisting of both casirivimab and imdevimab, is effective in the treatment of hospitalized COVID-19 patients, outpatients with COVID-19, and in post-exposure prophylaxis. A recent study posted on the medRxiv* preprint server assesses the efficacy of repeat monthly subcutaneous (SC) doses of REGEN-COV in SARS-CoV-2-negative adults who were healthy or had chronic medical conditions.
Study: Repeat Subcutaneous Administration of REGEN-COV® in Adults is Well-Tolerated and Prevents the Occurrence of COVID-19. Image Credit: PHOTOCREO Michal Bednarek / Shutterstock.com
About the study
The current study was a Phase 1, double-blind, and placebo-controlled study that was executed at seven sites throughout the U.S. and constituted a baseline/screening period, a treatment period, and a follow-up period of up to seven days, 24 weeks, and 28 weeks, respectively. There were 705 and 235 subjects in the REGEN-COV and placebo groups, respectively. The rationale for enrolling the 940 subjects in the study was to obtain sufficient safety data to support multiple REGEN-COV dose administration.
Eligible subjects were healthy adult volunteers between the ages of 18–90 years who were confirmed to be SARS-CoV-2 negative by central lab reverse transcription-polymerase chain reaction (RT-PCR) of nasopharyngeal swab before or within 72 hours of randomization. For the duration of the study, subjects who tested positive for SARS-CoV-2, elected to receive COVID-19 vaccination, or experienced an adverse event (AE) were excluded and moved to the follow-up stage.
All eligible subjects received up to six doses of either SC REGEN-COV 1,200 mg or placebo for four weeks. However, only those subjects who received more than 1 dose of REGEN-COV were classified in the REGEN-COV group.
Evaluating safety, pharmacokinetics, and immunogenicity of REGEN-COV
The primary endpoints assessed in the current study included the incidence of AEs of special interest (AESIs), as defined as grade ≥3 injection-site reactions (ISRs), or hypersensitivity reactions. AESIs occurred within four days of administration of REGEN-COV or placebo.
The secondary endpoints assessed the proportion of subjects with treatment-emergent AEs (TEAEs) and immunogenicity to REGEN-COV, which was measured using anti-drug antibodies (ADAs). Exploratory efficacy endpoints assessed the incidence and severity of symptomatic COVID-19 during the treatment and follow-up periods.
Risk of symptomatic SARS-CoV-2 infection during the treatment period. The proportion of subjects with the reported adverse event of SARS-CoV-2 infection compared to the number of subjects at risk for infection in the REGEN-COV group and placebo group is shown here by study day. Symptomatic SARS-CoV-2 (COVID-19) determination was made by the investigator on the basis of clinical assessment.
The effect of monthly doses of REGEN-COV
The current study was the first ever to investigate the effect of monthly doses of REGEN-COV. To this end, the current study findings demonstrate that monthly doses of REGEN-COV are well tolerated and could prevent COVID-19 for over six months.
As per the results of the exploratory efficacy analysis, REGEN-COV treatment resulted in a 92.4% relative risk reduction (RRR) in clinically defined COVID-19 and a 100% RRR in laboratory-confirmed COVID-19, which is strikingly similar to the risk reduction seen in the vaccine trials.
The results demonstrate a significant reduction in the production of SARS-CoV-2 anti-nucleocapsid immunoglobulin G (IgG) antibodies among REGEN-COV-treated subjects over the six-month course of therapy, as assessed by seroconversion rates. The observed seroconversion rate among placebo recipients was 9.6% and 0% among received REGEN-COV, thus suggesting that REGEN-COV is effective as a chronic treatment for immunocompromised individuals.
REGEN-COV-treated subjects showed a slightly higher frequency of ISRs as compared to placebo-treated patients, which suggests that multiple doses of REGEN-COV were well tolerated. The overall ISR rate with REGEN-COV was 36.5% across all six doses combined; however, the ISR rate between sites varied significantly and two outlier sites were driving forces behind these incidences.
Taken together, the assessments made in this study are consistent with a previous Phase III study and further establish the safety, tolerability, and efficacy of repeated monthly doses of SC-administered REGEN-COV. The current study reports that all ISRs were mild to moderate in severity and that repeated dosing did not increase the incidence and/or severity of ISRs. Furthermore, treatment-emergent immunogenicity remained low, while no grade ≥3 hypersensitivity reactions were reported.
It is important to note that during the study, the concentrations of casirimivab and imedivimab remained within the therapeutic range.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.