Limited Toxicity Seen With Leronlimab in Mild to Moderate COVID-19

Treatment with leronlimab (PRO 140) in patients with mild to moderate symptoms of respiratory illness from coronavirus disease 2019 (COVID-19) caused fewer serious adverse events (SAEs) when compared with placebo, according to safety results from a phase 2 clinical trial (NCT04343651).

The study is a randomized, multicenter, double-blind, placebo-controlled trial following a 2:1 randomization ratio. Out of the 84 patients enrolled in the study, 56 were randomized to receive leronlimab and 28 were accrued to the placebo arm. Both safety and efficacy were evaluated in the study, however, efficacy data will be reported later once all of the primary and secondary end points of the statistical analyses are finalized.

“We are very pleased with the safety results in the double-blinded, placebo-controlled study of the mild-to-moderate COVID-19 population. When considering treatment options in the COVID-19 population, it is paramount in treating this complex disease to provide patients with therapeutic options that minimize SAEs,” said Scott Kelly, MD, chief medical officer, CytoDyn, Inc, in a statement. “We believe the significant reduction in SAEs in the leronlimab group ultimately translates into improved patient clinical outcomes. Prior drugs in clinical trials for the treatment of COVID-19 have resulted in an increase in SAEs in the drug treated arm versus placebo. We are extremely proud of these results.”

The safety analysis showed that 34% of patients in the leronlimab arm experienced an AE versus 50% in the placebo arm. Of the AEs observed, 19 of them were SAEs. Six patients in the placebo arm were impacted by 11 SAEs (39%) compared with 5 patients in the leronlimab arm who experienced 8 SAEs (14%). These severe toxicities were not determined by the study investigators to be related to treatment with leronlimab. There was one patient death in the study related to an AE that was not caused by leronlimab.

“We are very pleased to see clear advantages for the patients in this population in leronlimab versus placebo in regard to SAEs and look forward to announcing all of the efficacy endpoints very soon,” Nader Purhassan, PhD, president and CEO, CytoDyn stated. “We are equally optimistic and look forward to the Data Safety Monitoring Committee’s upcoming review of the progress of our phase 3 trial for COVID-19 patients with severe and critical indications and remain hopeful the therapeutic benefits for this patient cohort will be consistent with the results we saw from the administration of leronlimab to over 60 patients under emergency Investigation New Drug authorizations previously granted by the US Food and Drug Administration.”

Target enrollment for this study is 75 patients, which has already been met. Patients will primarily be evaluated for clinical improvement, in terms of improvement in total symptom score. The key secondary end points of the study include time to clinical resolution, change from baseline in National Early Warning Score 2, pulse oxygen saturation, and health status on the ordinal scale. The study is also assessing the incidence of hospitalization, duration of hospitalization, incidence of mechanical ventilation supply and oxygen use, duration of oxygen use, mortality rate, and the time to return to normal activity. Exploratory outcomes being assessed in the study include the change in size of the lesion, and the change from baseline in serum cytokine/chemokine levels; CCR5 receptor occupancy level; and CD3-, CD4-, and CD8-positive T-cell count.

Patients with mild COVID-19 are those who had mild symptoms of the virus, like fever, rhinorrhea, mild cough, sore throat, malaise, headache, muscle pain, or malaise, but with no shortness of breath. Mild COVID-19 does not show signs of serious lower airway disease and these patients have an oxygen saturation respiratory rate (RR) <20, heart rate (HR) <90, or pulse oximetry of 93% on room air.

Unlike mild COVID-19, moderate COVID-19 is characterized by mild symptoms in addition to more significant lower respiratory symptoms and moderate pneumonia. Signs of moderate pneumonia include an RR of ≥20 but <30 and an HR of ≥90 but <125 as well as an oxygen saturation on room air of >93%. Patients are required to have these characteristics for either mild or moderate COVID-19 to enroll in the phase 2 study.

Leronlimab is a CCR5 antagonist that is primarily being investigated as treatment of triple-negative breast cancer. As a cancer agent, leronlimab plays a role in tumor invasion, limiting metastasis, and controlling the tumor microenvironment. In addition to being investigated in mild to moderate COVID-19, leronlimab is also being evaluated as treatment of critically ill patients with COVID-19.

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_{UPDATE - Impressive results from Cytodyn’s phase 2 covid-19 trial. News release. CytoDyn. July 21, 2020. Accessed July 21, 2020. https://bit.ly/3eO13xv}