Leronlimab COVID-19 Trial Kicks Off

Leronlimab is an investigational humanized IgG4 monoclonal antibody that blocks CCR5, a cellular receptor that appears to play multiple roles with implications in HIV infection, tumor metastases, and immune signaling.

The first 2 patients with COVID-19 have received treatment in a phase II trial exploring the investigational agent leronlimab (PRO 140), a CCR5 antagonist which has been advancing through the pipeline as a treatment for patients with triple-negative breast cancer (TNBC).1

Enrollment in the phase II COVID-19 study, which is accruing patients with mild-to-moderate symptoms, is expected to speed up at multiple clinical sites this week, CytoDyn, the company developing the agent, reported in a press release. The double-blind phase II study, which plans to accrue 75 patients, is randomizing individuals to leronlimab or placebo. Enrollment will occur at up to 10 clinical sites in the United States.

The company also reported in the press release that 15 patients with COVID-19 with severe symptoms have been treated with leronlimab under the FDA’s emergency investigational new drug (EIND) program. The treatment was administered in patients at 4 hospitals, including a major medical center in New York City.

“Our partnership with the New York medical team and now other hospitals has been exemplary. We are collaborating in every aspect to deliver leronlimab to patients in order to provide proof of concept as soon as possible. The outstanding coordination among the physicians, the hospital administrators, the FDA, and our team, will hopefully help mitigate the deleterious effects from this pandemic should we prove leronlimab as a solution,” Nader Pourhassan, PhD, president and chief executive officer of CytoDyn, stated in the press release.

“The lead physician in New York is a true medical hero, who deserves to be recognized for his contribution to humanity in the pandemic of COVID-19. We are very hopeful of sending the day three and day seven results of the first ten EIND patients to the FDA by the end of this week,” added Pourhassan.

CytoDyn also reported in the press release that the company plans to launch a double-blinded phase IIb/III trial soon that will accrue severely ill patients with COVID-19. Patients will be randomized in a 2:1 ratio to receive 2 weeks of leronlimab or placebo. The target enrollment is 342 patients and the primary endpoint will be the 14-day mortality rate.

“We are encouraged by the positive results demonstrated with leronlimab in the New York patients. Our team is working hard to distribute leronlimab to multiple clinical sites to initiate therapy in patients with severe COVID-19 disease. While every patient is experiencing different comorbidities, we are seeing similar clinical responses, which we believe is a reflection of leronlimab’s mechanism of action,” Bruce Patterson, MD, chief executive officer and founder of IncellDx, a diagnostic partner and advisor to CytoDyn, stated in the press release.

Beyond leronlimab, several investigational and approved drugs used in oncology, including tocilizumab (Actemra) and ruxolitinib (Jakafi), are being explored as COVID-19 treatments, as medical professionals across all fields continue to collaborate in an attempt to contain the crisis.

Leronlimab is an investigational humanized IgG4 monoclonal antibody that blocks CCR5, a cellular receptor that appears to play multiple roles with implications in HIV infection, tumor metastases, and immune signaling.

Prior research has shown that CCR5 potentially plays a central role in tumor invasion and metastasis and that increased CCR5 expression is an indicator of disease status in several cancers. Additional data demonstrated that CCR5-blocking drugs can block tumor metastases in laboratory and preclinical models of aggressive breast and prostate cancer.

Earlier this month, CytoDyn reported that it is planning to meet with the FDA to share data in support of a breakthrough therapy designation for leronlimab for the treatment of patients with metastatic TNBC.2 Leronlimab is currently being explored in a phase Ib/II study in metastatic TNBC, as well as in expanded access studies for metastatic breast cancer. In the TNBC study, the activity of leronlimab is being assessed through the monitoring of circulating tumor cells, epithelial mesenchymal transition in tumor metastasis, and cancer-associated microphages like cells.

Leronlimab previously received a fast track designation from the FDA.3 The FDA’s fast track and breakthrough therapy designations are intended to expedite the development and review of promising new therapies, particularly for diseases with an unmet medical need. Beyond TNBC, leronlimab is also being explored in a phase II trial that is accruing patients across 22 solid tumor types.

CytoDyn also explained in the press release that the CCR5 receptor also potentially has a central role in modulating immune cell trafficking to inflammation sites, and it may be crucial for the development of acute GVHD and other inflammatory conditions. According to the company, blocking CCR5 with a chemical inhibitor can reduce the clinical impact of acute GVHD without affecting the engraftment of transplanted bone marrow stem cells. For this reason, leronlimab is also being examined in a GVHD trial.

References

1. First Two Patients Enrolled in Randomized Phase 2, COVID-19 Trial with Leronlimab; Five More Severely Ill COVID-19 Patients Treated Under Emergency IND and Two Patients Have Already Extubated. Published April 6, 2020. https://bit.ly/39RZQCB. Accessed April 6, 2020.

2. CytoDyn Files Request with FDA for Preliminary Meeting for Breakthrough Therapy Designation for Leronlimab in the Treatment of Cancer. Published April 3, 2020. https://bit.ly/2yFcOa9. Accessed April 6, 2020.

3. FDA Grants CytoDyn Fast Track Designation for Leronlimab (PRO 140) in metastatic Triple-Negative Breast Cancer, an Unmet Medical Need. CytoDon. Published May 7, 2019. https://bit.ly/2DWHsLT. Accessed May 7, 2019.