Leronlimab Appears to Prevent Progression to Severe or Critical COVID-19

Findings from the phase 2 CD10 study of leronlimab (PRO 140), an agent that has been used to treat various solid tumors and hematologic malignancies, as treatment of patients with mild-to-moderate coronavirus disease 2019 (COVID-19) suggest the agent can prevent progression to severe or critical disease, according to a presentation during the Special isirv-Antiviral Group Conference on ‘Therapeutics for COVID-19’.

Overall, leronlimab induced a reduction in the National Early Warning Score 2 (NEWS2) at day 14, although the trial saw no differences in oxygen use or hospitalizations in the placebo arm of the study, which may have been limited due to exclusion of patients with pre-existing medical conditions, such as severe pulmonary, liver, and renal disease who have been shown to be at higher risk of COVID-19 progression and overall mortality.

“[This is] a safe monoclonal blocking a novel target that promotes immunity to clear infection and limit inflammation,” Harish Seethamraju, MD, medical director, Advanced Lung Failure & Lung Transplant, Monefiore Medical Center, told Targeted Oncology. He also explained that leronlimab “has beneficial effects beyond COVID-19 disease.”

The study (NCT04343651) is a double-blinded, randomized trial and included 86 patients with mild-to-moderate symptoms of respiratory illness caused by COVID-19, who were randomized to receive either leronlimab 700 mg (n = 56) or placebo (n = 29). The majority of patients were female overall (60.7%), as well as in the leronlimab (57.1%) and placebo (67.9%) arms. The median age in the study was 55.5 (range, 23-84).

At baseline, the Total Symptom Score (TSS) Group was ≤4 in 53.6% of the population and >4 in 46.4%. The majority of patients (76.2%) had not received any off-label COVID-19 treatments. Overall, 61.9% were aged <60 years, and the majority (66.7%) had never smoked.

The primary end point in the study was measured clinical improvement by assessing the change in TSS. Symptoms assessed included fever, myalgia, dyspnea, and cough. Among patients with TSS ≤4 at baseline, 90% of those treated with leronlimab reported improvements in total clinical symptom score at day 3 compared with 71% in the placebo arm. In the modified intent-to-treat (mITT) population, 63% in the leronlimab versus 56% in the placebo arm had clinical improvements.

The NEWS2 score was based on clinical parameters, which included respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, and level of consciousness. Among patients in the mITT population, 50% of patients who received leronlimab versus 20.83% in the placebo arm experienced improved NEWS2 scores by the end of treatment or day 14, and the difference was statistically significant (P =.0223). In the per protocol population, 42% of patients in the leronlimab arm versus 14% in the placebo arm had improved scores, which was also statistically significant (P =.0282).

Any grade adverse events (AEs) were observed in 33 patients (39.3%) overall, while mild events occurred in 17 (20.2%), moderate events in 8 (9.5%), and severe in 8 (9.5%). In the leronlimab arm, the incidence, frequency, and severity of AEs were lower compared with placebo, in which AEs of any grade were observed in 19 patients (33.9%) versus 14 (50.0%), of mild severity in 12 (21.4%) versus 5 (17.9%), moderate in 2 (3.6%) versus 6 (21.4%), and severe in 5 (8.9%) versus 3 (10.7%), respectively.

Treatment-emergent AEs (TRAEs) were observed in 11 patients (13.1%) overall, including 5 (8.9%) in the leronlimab and 6 (21.4%) in the placebo arm. TEAEs that were possibly related to study treatment were observed in 2 patients (7.1%) of patients in the placebo arm versus none in the chemotherapy arm. TEAEs that were unrelated to the study treatment were observed in 5 patients (8.9%) who received leronlimab versus 4 (14.3%) in the placebo arm.

Overall, 8 serious AEs occurred in 56 patients (14%) in the leronlimab arm compared with 11 in 28 patients (39%) from the placebo arm.

Leronlimab has demonstrated previously its ability to concurrently downregulate pathologic inflammatory responses and restore immune homeostasis in patients with severe COVID-19. Additional studies are needed to understand the therapeutic benefit of this therapy in healthy patients with mild to moderate disease, which will require broader eligibility criteria to include those with a higher risk of disease progression.

The study includes 3 phases: a screening period, treatment period, and follow-up period. To be included in the study, patients had to be over the age of 18 at the time of enrollment with mild-to-moderate symptoms of respiratory illness caused by a COVID-19 infection. Mild symptoms include fever, rhinorrhea, mild cough, sore throat, malaise, headache, muscle pain, or malaise, but with no shortness of breath. Moderate symptoms included the same symptoms, as well as more significant lower respiratory symptoms, including shortness of breath, or moderate pneumonia.

Patients showing signs of acute respiratory distress syndrome or respiratory failure requiring mechanical ventilation at the time of screening were not permitted into the study, nor were patients with severe chronic respiratory disease and requirements for long-term oxygen therapy. Patients also could not have signs of clinical jaundice at screening, a history of moderate and severe liver disease, history of severe chronic kidney disease or requiring dialysis, or required Renal Replacement Therapy at the time of screening.

Leronlimab is currently being explored as treatment of patients with metastatic triple-negative breast cancer, and the agent has also received an Orphan Drug designation for the prevention of graft-versus-host disease based on preclinical findings.

_Reference

_{Seethamraju H, Recknor C, Otto Y, et al. A Phase 2 Study of Leronlimab for Mild to Moderate Coronavirus Disease 2019 (COVID-19). Presented during: Antiviral Group virtual Conference on ‘Therapeutics for COVID-19’; October 6-8, 2020; Virtual.}