REGEN-COV® Trial Summary

Hospitalized COVID-19 patients reported having high mortality rates (10-30%). Casirivimab and imdevimab antibody cocktail (REGEN-COV®) are authorized in various countries for use in outpatients with COVID-19 and in post-exposure prophylaxis. The current trial was an adaptive, phase 1/2/3, double-blinded, placebo-controlled trial to evaluate the efficacy, safety, and tolerability of REGEN-COV in hospitalized adult patients with COVID-19 (on low-flow or no supplemental oxygen). The study was conducted at 103 sites in the United States, Brazil, Chile, Mexico, Moldova, and Romania.

A total of 1336 patients were included, who were 18 years or older and hospitalized with confirmed SARS-CoV-2 ≤72 hours with symptom onset ≤10 days from randomization. Standard-of-care treatments for COVID-19, as per the investigator, were permitted. Patients were randomized (1:1:1) to 2.4 g or 8.0 g REGEN-COV or placebo and characterized at baseline for viral load and SARS-CoV-2 endogenous immune response. The primary virologic efficacy endpoint was the time-weighted average (TWA) the daily change in viral load. The primary clinical efficacy endpoint was the proportion of patients who died or required mechanical ventilation from day 6-29 and day 1-29. Secondary efficacy endpoints examined all-cause mortality and discharge from/readmission to hospital. Safety endpoints included the proportion of patients with treatment-emergent SAEs and adverse events of special interest (AESIs).

Results

The median age was 62 years, 54.1% were male, mean BMI was 31.1 kg/m², 12.1% identified as Black/African American, and 30.1% identified as Hispanic/Latino.

Virologic Efficacy

REGEN-COV significantly reduced viral load in seronegative patients on low-flow or no supplemental oxygen:

• TWA daily change in viral load from baseline through day 7: -1.03 log₁₀ copies/mL (CI: -1.22, -0.84) in placebo vs –1.31 log₁₀ copies/mL (CI: -1.43, -1.18) in REGEN-COV group (P=0.0172).
• Both doses of REGEN-COV exhibited similar viral load reductions, showing improvement over placebo starting at day 3 and reaching significance at day 7.
• The maximum least-squares (LS) mean differences vs. placebo in seronegative patients were at day 7 (-0.28 log₁₀ copies/mL), day 9 (–0.47 log₁₀ copies/mL, CI: -0.71, -0.23), and day 11 (-0.59 log₁₀ copies/mL CI: -0.85, -0.34).

Clinical Efficacy

• Death or mechanical ventilation: Treatment with REGEN-COV reduced the proportion of patients who died or required mechanical ventilation, with improvement from day 1-29 in the high-viral load (RRR, 35.0%; 95% CI: 6.6%, 54.8%), seronegative (RRR, 47.0%; 95% CI: 17.7%, 65.8%), and overall (RRR, 30.9%; 95% CI, 5.4% to 49.5%) populations. The primary clinical analysis of death or mechanical ventilation from day 6-29 in patients with high-viral load had a strong positive trend but did not reach significance.
• All-cause mortality: Treatment with REGEN-COV led to improvement in all-cause mortality through day 29 in the seronegative, high-viral load, and overall populations. The greatest reduction in relative risk of death occurred in seronegative patients; 24/360 (6.7%) died within 28 days in the REGEN-COV group, compared to 24/160 (15.0%) in the placebo group (RRR, 55.6%; 95% CI: 24.2%, 74%).

Safety

• SAEs were experienced by more patients in the placebo group compared to the REGEN-COV group for patients on low-flow oxygen (131/469 [27.9%] placebo vs. 224/941 [23.8%] REGEN-COV) and no supplemental oxygen (43/198 [21.7%] placebo vs. 61/399 [15.3%] REGEN-COV).
• More patients experienced treatment-emergent adverse events that resulted in death in the placebo group compared with REGEN-COV for both patients on low-flow oxygen (72/469 [15.4%] placebo vs. 108/941 [11.5%] REGEN-COV) and no supplemental oxygen (15/198 [7.6%] placebo vs. 15/399 [3.8%] REGEN-COV).
• No safety concerns were noted overall nor in seropositive patients.

In hospitalized patients with Covid-19 on low-flow or no oxygen, REGEN-COV treatment reduced viral load and the risk of death or mechanical ventilation as well as all-cause mortality in the overall population, with the benefit driven by seronegative patients and no harm observed in seropositive patients.

For more details about the prescribing information, click here

Reference: Somersan-Karakaya S et al. REGEN-COV® for Treatment of Hospitalized Patients with Covid-19. medRxiv 2021.11.05.21265656; doi: https://doi.org/10.1101/2021.11.05.21265656.

Disclaimer

This article has been published under MD Brand Connect Initiative.

This content and information provided is intended for update strictly for Registered Medical Practitioners/ Physicians treating Covid 19 only. The information mentioned herein is not intended nor implied to be a substitute for professional medical advice. Any advice regarding the management of any medical condition is totally in the discretion of doctor (Registered Medical Practitioner)/ physician treating Covid 19 patients. Prescription of the drug is the prerogative of doctors (Registered Medical Practitioner/ Physician treating Covid 19) at his /her sole discretion. Physicians treating Covid 19 patients must refer to the full prescribing information of the product for use of product. Copying, reproduction, circulation of the information published here in any form or by any means either mechanically/ print or electronically without prior consent is strictly prohibited. Any unauthorized person having possession of this document should discard the same or inform/ notify/ return to Cipla Ltd. To report any adverse events/special situation with Cipla medicinal products email at drugsafety@cipla.com or via the national Pharmacovigilance Programme of India by calling on 1800267 7779 (Cipla number) or you can report to PvPI on 1800 180 3024. By reporting side effects, you can help provide more information on the safety of this product. For complete prescribing information, please login www.ciplamed.com.