HIV: CytoDyn plans for application's resubmission to FDA for Leronlimab in Highly Treatment-Experienced HIV Patients

CytoDyn Inc., a late-stage biotechnology company developing leronlimab, a CCR5 antagonist with the potential for multiple therapeutic indications, announced on Jly 1st 2021 to have submitted a dose justification report to the U.S. Food and Drug Administration (“FDA”), which will be followed by an official submission to CytoDyn’s IND. This is an integral step in the resubmission process for the Biologics License Application (“BLA”) for HIV patients with multiple resistance to current standard of care.

The dose justification report is a key component for the BLA and includes receptor occupancy analysis, among other factors, to determine the optimal marketed dose for leronlimab. Following FDA feedback on this critical step, CytoDyn will begin submission of BLA modules by specified timelines in accordance with FDA guidance and approval. 

Chris Recknor, M.D., CytoDyn’s Chief Operating Officer and Head of Clinical Development, commented "we have a great molecule with many opportunities being evaluated in parallel to the BLA, including COVID, NASH and Oncology. We are on track for the top line report for the COVID-19 long-haulers symptoms/biomarker trial and will soon start two COVID-19 trials in Brazil. Our Phase 2 NASH trial has enrolled the 60th patient on schedule. We are working on our CCR5 solid tumor cancers basket trial and our triple-negative breast cancer dose escalation portion is completed with the main trial beginning in July". 

The U.S. Food and Drug Administration (FDA) granted CytoDyn Fast Track designation for Leronlimab to explore two potential indications using leronlimab to treat Human Immunodeficiency Virus (HIV) and metastatic cancer. The first indication is combination therapy with HAART for HIV-infected patients, and the second is for metastatic triple-negative breast cancer (mTNBC).

Leronlimab is an investigational humanized IgG4 mAb that binds to CCR5, a cellular receptor important in HIV infection, tumor metastases, and other diseases, including nonalcoholic steatohepatitis (NASH).

Leronlimab, among various potential applications, is a viral-entry inhibitor in HIV/AIDS. It binds to CCR5, thus protecting healthy T cells from viral infection by blocking the predominant HIV (R5) subtype from entering those cells. Leronlimab does not work on other strains of HIV (for example X4), however, R5 is the most dominant strain of HIV.

Five clinical trials have demonstrated leronlimab could significantly reduce or control HIV viral load in humans. The leronlimab antibody appears to be a powerful antiviral agent with fewer side effects and less frequent dosing requirements than currently used daily drug therapies. 

Cancer research has shown CCR5 may play a role in tumor invasion, metastases, and tumor microenvironment control (for example, through angiogenesis). Published studies have shown that blocking CCR5 can reduce tumor metastases in laboratory and animal models of aggressive breast and prostate cancer. Leronlimab reduced human breast cancer metastasis by more than 97% in a murine xenograft model. As a result, CytoDyn is conducting two clinical trials, one, a Phase 1b/2 in mTNBC, which was granted Fast Track designation by the FDA in 2019, and a second, a Phase 2, basket trial which encompasses 22 different solid tumor cancers.

The CCR5 receptor plays a central role in modulating immune cell trafficking to sites of inflammation. After completing two clinical trials with COVID-19 patients (a Phase 2 and a Phase 3), CytoDyn initiated a Phase 2 investigative trial for post-acute sequelae of SARS COV-2 (PASC), also known as COVID-19 Long-Haulers. This trial will evaluate the effect of leronlimab on clinical symptoms and laboratory biomarkers to further understand the pathophysiology of PASC. It is currently estimated that between 10-30% of those infected with COVID-19 develop long-term sequelae. Common symptoms include fatigue, cognitive impairment, sleep disorders, and shortness of breath. If this trial is successful, CytoDyn plans to pursue clinical trials to evaluate leronlimab’s effect on immunological dysregulation in other post-viral syndromes, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

CytoDyn is also conducting a Phase 2 clinical trial for NASH to evaluate the effect of leronlimab on liver steatosis and fibrosis. Preclinical studies revealed a significant reduction in NAFLD and a reduction in liver fibrosis using leronlimab. There are currently no FDA approved treatments for NASH, which is a leading cause of liver transplant. About 30 to 40 percent of adults in the U.S. live with NAFLD, and 3 to 12 percent of adults in the U.S. live with NASH. There have been no strong safety signals identified in patients administered leronlimab in multiple disease spectrums, including patients with HIV, COVID-19, and oncology.