Could the investigational drug leronlimab prevent the deadly “cytokine storm” that threatens some severe COVID-19 patients? That is the hope as Montefiore Health System and Albert Einstein College of Medicine and several other prominent centers represent the first clinical investigational sites in America to investigate the drug in a COVID-19 setting in two separate U.S. Food and Drug Administration approved trials. One study involves patients with mild-to-moderate cases of SARS-CoV-2 while the other deals with severe cases.
The Problem with COVID-19
The advent of SARS-CoV-2, the virus behind the COVID-19 pandemic, has led to over 100,000 deaths in America alone. Although the majority of those that contract SARS-CoV-19 experience mild to moderate symptoms, a subset of patient will progress to a severe and dangerous disease with pneumonia and acute respiratory distress disorder (ARDS) requiring mechanical ventilation. Preliminary results of research suggest a dysregulated immune response evidenced by runaway inflammation such as cytokine release syndrome, as the major driver of pathology in severe and critical COVID-19. There are no accepted treatments presently approved by the U.S. Food and Drug Administration (FDA); novel therapeutics are urgently needed. A recent write up by Medical Dialogues showcased the potential of this experimental monoclonal antibody therapy.
The Investigational Drug
Leronlimab (PRO 140) is a humanized monoclonal antibody targeted against the CCR5 found on T lymphocytes on the human immune system. It is being investigated as a potential therapy in the treatment of HIV infection. The FDA designated PRO 140 for fast track approval in May 2019.
The Compassionate Use Cases Leading to the Study
A multicenter team, led by Montefiore Health System, were caring for 10 terminally-ill, critical COVID-19 patients with very high elevation of plasma IL-6 and CCL5 (biomarker for inflammation), as well as decreased CD8+ T cell levels and SARS-CoV-2 plasma viremia. After the U.S. Food and Drug Administration (FDA) awarded a compassionate care treatment with the CCR5 blocking antibody leronlimab, the investigators observed complete CCR5 receptor occupancy on macrophage and T cells, rapid reduction of plasma IL-6, restoration of CD4/CD8 ration and a significant decrease in SARS-CoV-2 plasma viremia. They reported their findings in a published document uploaded to preprint server MedRxiv. They articulated that the results represent a novel approach to resolving unchecked inflammation, restoring immunologic deficiencies and reducing COVID-19 symptoms—thus supporting an actual randomized trial to assess the clinical efficacy of leronlimab-mediated inhibition of CCR5 for COVID-19.
A Key Principal Investigator
Harish Seethamraju, MD, is an organ transplant specialist and member of department of medicine at Montefiore and Einstein who now serves as a principal investigator for the full study. Based on a recent report from Medical Dialogue, Dr. Seethamraju is bullish on this approach—one that evidences promise based on the compassionate use study. He is hopeful that the drug can prevent the cytokine storm that not only causes organ damage but can lead to death. Dr. Seethamraju was a key participant in the compassionate use study that led to the FDA approved clinical trial.
The study for mild-to-moderate cases started April 1 and the study team expects an estimated primary completion date of December 4, 2020. This study seeks 75 participants. While the second study focusing on severe hospitalized COVID-19 cases commenced mid-April and is targeting 390 participants, the study’s estimated primary completion date, December 31, is followed by an estimated study completion data of April 1, 2021.
In addition to Montefiore Health System and Albert Einstein College of Medicine, other participating sites include UCLA, Eisenhower Health in California, Yale in Connecticut, Beth Israel and Harvard in Massachusetts; St. Barnabas and Atlantic Health System Hospital in New Jersey; Novant Health, North Carolina; Ohio Health; Oregon Health and Sciences University, Oregon; and University of Texas in Houston.
Dr. Seethamraju serves as co-principal investigator at Montefiore along with Scott A. Scheinin, MD, surgical director of advanced pulmonary failure and lung transplantation, division of thoracic surgery and surgical oncology.
CytoDyn, Inc., the makers of leronlimab, is a late-stage biotech company advancing targeted therapies to address cancer, HIV, and other autoimmune diseases with the goal of improving the quality of life for patients and simplifying treatment plans. In oncology, CytoDyn is conducting a Phase 1b/2 clinical trial to evaluate its targeted therapy for the treatment of metastatic triple-negative breast cancer, the most aggressive type of breast cancer. In HIV, CytoDyn has successfully completed a Phase 3 pivotal trial with its investigational treatment in combination with standard anti-retroviral therapies. CytoDyn is also conducting a Phase 3 investigative trial for its targeted therapy as a once-weekly monotherapy for HIV. In autoimmune diseases, CytoDyn is conducting a Phase 2 trial for the prevention of graft-versus-host disease (GvHD) and is currently enrolling patients for a Phase 2 trial for the treatment of Nonalcoholic steatohepatitis (NASH).
A corporate presentation can be viewed here.
Lead Research/Investigator (Montefiore and Albert Einstein)
Scott A. Scheinin, MD, surgical director of advanced pulmonary failure and lung transplantation, division chief of thoracic surgery and surgical oncology, and director of the Bloodless Heart Surgical Program at Montefiore.
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