CytoDyn Receives Positive DSMC Recommendation After Interim Analysis For Leronlimab Phase 2b/3 Covid-19 Registrational Trial

Published : 30 Oct 2020

Drug Name: leronlimab

CytoDyn Inc., a late-stage biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced recommendations from the Data Safety Monitoring Committee (DSMC) following its review of the interim analysis of the Company’s Phase 2b/3 registrational trial in patients with severe-to-critical COVID-19. The interim analysis was performed on data from the first 195 (50%) of 390 planned patients.

The DSMC had three recommendations to consider following its review of the interim analysis:

1. Stop the trial due to safety concerns;

2. Continue the trial with modification (i.e., increase the sample size to maintain the power to achieve the primary endpoint); or

3. Continue the study as planned, with the protocol defined sample size and power to achieve the primary endpoint.

The DSMC recommends the trial continue without modification to achieve the primary endpoint and request another interim analysis when enrollment reaches 75% level (or 293 patients) to review patient mortality and other clinical outcome data between the two study arms (leronlimab vs. placebo). Trial enrollment is currently at 230 patients. The Company is working diligently to accelerate patient enrollment in the U.S. and U.K. to achieve the enrollment goal of 293 patients as quickly as possible (potentially in 4-6 weeks), with the goal of full enrollment (390) before year-end. Clinical trial sites in the U.K. are expected to initiate enrollment in the coming days.

CytoDyn’s Phase 2b/3 trial to evaluate the efficacy and safety of leronlimab for patients with severe-to-critical COVID-19 indications is a two-arm, randomized, double-blind, placebo-controlled, adaptive design multicenter study. Patients are randomized to receive weekly doses of 700 mg leronlimab or placebo. Leronlimab and placebo are administered via subcutaneous injection. The study has three phases: Screening Period, Treatment Period, and Follow-Up Period. The primary outcome measured in this study is all-cause mortality at Day 28. Secondary outcomes measured are (1) all-cause mortality at Day 14, (2) change in clinical status of subject at Day 14, (3) change in clinical status of subject at Day 28, and (4) change from baseline in Sequential Organ Failure Assessment (SOFA) score at Day 14.

CytoDyn’s President and Chief Executive Officer, Nader Pourhassan, Ph.D., stated, “We are grateful to the DSMC members for their diligence, guidance, and support. We are very pleased by the DSMC’s recommendation and this encouraging interim analysis adding to the promising data already demonstrated with emergency INDs in over 60 severe and critical COVID-19 patients. Concurrently, we are seeking ongoing guidance from the U.S. Food and Drug Administration and regulatory agencies in other countries for a swift regulatory approval pathway for leronlimab to treat COVID-19.

During today’s webcast, we will discuss in-depth ll of our priorities dedicated to advancing leronlimab as a therapeutic for COVID-19 and all of the opportunities that could be available to us in the coming months.” Dr. Pourhassan added, “We look forward to providing additional information during today’s webcast.”

About Leronlimab (PRO 140)

The FDA has granted a Fast Track designation to CytoDyn for two potential indications of leronlimab for critical illnesses. The first indication is combination therapy with HAART for HIV-infected patients and the second is for metastatic triple-negative breast cancer. Leronlimab is an investigational humanized IgG4 mAb that blocks CCR5, a cellular receptor that is important in HIV infection, tumor metastases, and other diseases, including NASH. Leronlimab has completed nine clinical trials in over 800 people and met its primary endpoints in a pivotal Phase 3 trial (leronlimab in combination with standard antiretroviral therapies in HIV-infected treatment-experienced patients).

In the setting of HIV/AIDS, leronlimab is a viral-entry inhibitor; it masks CCR5, thus protecting healthy T cells from viral infection by blocking the predominant HIV (R5) subtype from entering those cells. Leronlimab has been the subject of nine clinical trials, each of which demonstrated that leronlimab could significantly reduce or control HIV viral load in humans. The leronlimab antibody appears to be a powerful antiviral agent leading to potentially fewer side effects and less frequent dosing requirements compared with daily drug therapies currently in use.

In the setting of cancer, research has shown that CCR5 may play a role in tumor invasion, metastases, and tumor microenvironment control. Increased CCR5 expression is an indicator of disease status in several cancers. 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 98% in a murine xenograft model. CytoDyn is, therefore, conducting a Phase 1b/2 human clinical trial in metastatic triple-negative breast cancer and was granted Fast Track designation in May 2019.

The CCR5 receptor appears to play a central role in modulating immune cell trafficking to sites of inflammation. It may be crucial in the development of acute graft-versus-host disease (GvHD) and other inflammatory conditions. Clinical studies by others further support the concept that blocking CCR5 using a chemical inhibitor can reduce the clinical impact of acute GvHD without significantly affecting the engraftment of transplanted bone marrow stem cells. CytoDyn is currently conducting a Phase 2 clinical study with leronlimab to support further the concept that the CCR5 receptor on engrafted cells is critical for the development of acute GvHD, blocking the CCR5 receptor from recognizing specific immune signaling molecules is a viable approach to mitigating acute GvHD. The FDA has granted orphan drug designation to leronlimab for the prevention of GvHD.

Source: GlobalData.com