Regdanvimab—A New Attack of the (Mono)Clones

As new variants of the SARS-CoV-2 virus emerge, it is imperative that novel, active therapeutics are available for treatment or prevention. Regdanvimab (CT-P59) is a neutralizing antibody that was studied in a phase 2/3 trial (NCT04602000) in outpatients with mild to moderate infections of COVID-19.¹ Results from part 1 of the study, regarding SARS-CoV-2 suppression and patient effects for 180 days after administration, are currently available.

Patients were enrolled between October and December 2020 if they were 18 years or older, had an oxygen saturation of greater than 94% on room air, did not require supplemental oxygen, and received a diagnosis of mild to moderate COVID-19. Patients were within 7 days of symptom onset and within 48 hours of fever, cough, shortness of breath, sore throat, body aches, or headache. Patients were randomized to regdanvimab 40 mg/kg, regdanvimab 80 mg/kg, or placebo. The study drug was infused intravenously over 90 minutes. The primary end points were time to conversion to negative nasopharyngeal swab (day 28) and time to clinical recovery (day 14). Secondary end points included requiring hospitalization and/ or requiring oxygen therapy and/or death due to COVID-19. Sample size estimates predicted 100 patients in each arm to achieve statistical significance with 80% power.

Baseline demographic and disease characteristics were well matched. Patients were mostly white adults aged 51 to 52 years old, with 88% enrolled from European countries. Approximately 55% to 60% had moderate disease, with 70% possessing risk factors for progression to severe disease.

There were no differences among groups for time to conversion to negative polymerase chain reaction, set at a threshold of less than 2.33 log10 copies/mL (Table). When the threshold was set to less than 3.0 log10 copies/mL, the regdanvimab groups achieved negativity approximately 3 days faster. Additionally, more participants in the regdanvimab groups achieved negative conversion by days 14 and 28 than those in the placebo group. Median time to recovery was shorter in the regdanvimab groups than those in the placebo group (5.7 vs 8.8 days).

Regdanvimab reduced the proportion of patients who required hospital admission, supplemental oxygenation, and rescue therapy (Table). The medications were well tolerated, with similar proportions reported in each group (25%-30%) and no all-cause mortalities. Low percentages (4.5%-6.7%) were attributed to the study drug, and no participant discontinued therapy because of adverse effects. One infusion-related reaction was reported in the regdanvimab 40 mg/kg group and 2 were reported in the placebo group.

These results are promising, but as this study was conducted prior to the authorization of vaccines, the entire study population was unvaccinated. The benefits seen in a vaccinated population can be assumed to be fewer. This was also prior to the emergence of several virulent strains, such as Delta and Omicron. Additional in vitro simulations predict regdanvimab would retain activity against Delta but not Omicron.^2,3

Regdanvimab may have limited use against current circulating strains, but this pandemic has proven it is nearly impossible to predict the next iteration of the virus. A mutation may create a variant that is once again susceptible to some of the previous therapeutics. Therefore, the results of part 2 of this study and the phase 3 portion that examines the clinical effects of regdanvimab are eagerly awaited.

If proven effective against future SARS-CoV-2 variants and authorized to treat COVID-19, regdanvimab would expand the options available to clinicians and patients. However, administration may be challenging. Because regdanvimab is intended for outpatients, developing protocols and finding locations where patients with active COVID-19 infections can acquire this intravenous infusion is key. Finding clinicians who can administer the product may also be a challenge, as the health care workforce has been stretched thin. Although the 9th Amendment to the Public Readiness and Emergency Preparedness (PREP) Act authorized pharmacists to administer approved COVID-19 therapeutics, they were limited to oral, intramuscular, or subcutaneous routes of administration.⁴ Even if regdanvimab was proven to be effective, pharmacists would be barred from ordering and administering this therapy.

References

1. Streinu-Cercel A, Săndulescu O, Preotescu LL, et al. Efficacy and safety of regdanvimab (CT-P59): a phase 2/3 randomized, double-blind, placebo-controlled trial in outpatients with mild-to-moderate coronavirus disease 2019. Open Forum Infect Dis. 2022;9(4):ofac053. doi:10.1093/ofid/ofac053
2. Ryu DK, Kang B, Noh H, et al. The in vitro and in vivo efficacy of CT-P59 against Gamma, Delta and its associated variants of SARS-CoV-2. Biochem Biophys Res Commun. 2021;578:91-96. doi:10.1016/j.bbrc.2021.09.023
3. VanBlargan LA, Errico JM, Halfmann PJ, et al. An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies. Nat Med. 2022;28(3):490-495. doi:10.1038/s41591-021-01678-y
4. Expanding access to COVID 19 therapeutics. Public Health Emergency. Reviewed September 21, 2021. Accessed March 20, 2022. https://www.phe.gov/Preparedness/legal/prepact/Pages/PREPact-NinethAmendment.aspx