Vyrologix Leronlimab 2024
CytoDyn's Vyrologix™ (Leronlimab, PRO 140) is a CCR5 antagonist with the potential for multiple therapeutic indications such as cancer and HIV. It belongs to a new class of therapeutics, CCR5 antagonist, protecting healthy cells from viral infection. The CCR5 receptor plays a central role in modulating immune cell trafficking to sites of inflammation. CCR5 plays a critical role in the ability of HIV to enter and infect healthy T-cells. In addition, it appears to be implicated in tumor metastasis and immune-mediated illnesses, such as NASH. Vyrologix is a humanized monoclonal antibody targeted against the CCR5 receptor found on T lymphocytes of the human immune system. Due to Vyrologix-Leronlimab selectivity and target-specific mechanism of action, this monoclonal antibody allows chemokine binding (CCL3, CCL4) at therapeutic doses and does not activate the immune function of the receptor.
For HIV, Vyrologix (Leronlimab) is a viral-entry inhibitor in HIV, 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.
On November 19, 2021, Frontiers in Immunology published the results of an Original Research study that Established two CCR5 receptor occupancy calculation methods for longitudinal monitoring of anti-CCR5 therapeutic antibody blockade efficacy in both macaques and humans; Demonstrated that CCR5+CD4+ T cell levels temporarily increase with leronlimab treatment; and; Facilitate future detailed investigations into the immunological impacts of CCR5 inhibition in multiple pathophysiological processes. On April 22, 2022, Clinical Infectious Diseases published a Brief Report: Infectious Diseases Society of America: Reduced Cell Surface Levels of C-C Chemokine Receptor 5 and Immunosuppression in Long Coronavirus Disease 2019 Syndrome.
The U.S. FDA has designated Leronlimab (Pro 140) for Fast Track Approval to treat HIV and metastatic cancer. In July 2021, CytoDyn announced that it had submitted a dose justification report to the FDA, an integral step in the resubmission process for a BLA. On February 22, 2022, the Office of Prescription Drug Promotion of the FDA issued a Warning Letter: 'the video misbrands leronlimab under section 502(f)(1) of the FD&C Act and in violation of section 301(a) of the FD&C Act. The claims in the video are concerning because they make representations in a promotional context regarding the safety and efficacy of an investigational new drug that has not been approved or authorized by the FDA.' On March 30, 2022, the FDA placed a full clinical hold on the program. On February 29, 204, CytoDyn Inc. announced today that the FDA has lifted the clinical hold on leronlimab. The Company is now free to proceed with its proposed HIV clinical trial exploring leronlimab and its effects on chronic inflammation.
Molecular Formula: C6534 H10036 N1720 O2040 S42. U.S. NIH Chemical Name: Immunoglobulin G4, anti-(human Chemokine receptor CCR5) (humanized monoclonal PRO 140 γ4-chain), disulfide with humanized monoclonal PRO 140 κ-chain, dimer; Molecular Formula: C6534 H10036 N1720 O2040 S42 (non-glycosylated).
Vancouver, Washington-based CytoDyn (OTCQB: CYDY) is a late-stage biotechnology company developing innovative treatments for multiple therapeutic indications using leronlimab, a novel humanized monoclonal antibody targeting the CCR5 receptor. CytoDyn's CEO, Dr. Jacob Lalezari, is hosting an investment community webcast to provide a Company update on Tuesday, March 5, 2024.
Leronlimab Indication for HIV
Leronlimab is a viral-entry inhibitor in HIV/AIDS. In the setting of HIV, 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, demonstrating that leronlimab could significantly reduce or control HIV viral load in humans. On October 28, 2022, CytoDyn Inc. announced that it has voluntarily withdrawn its pending BLA for leronlimab as a combination therapy in persons living with HIV with resistance to highly active antiretroviral therapy (HAART) in the HIV multi-drug resistant population (HIV-MDR). On March 30, 2022, the FDA placed a partial clinical hold on the HIV program.
Announced on July 8, 2022, a five-year grant of up to $5 million was awarded to OHSU by the National Institute of Allergy and Infectious Diseases. A new pre-clinical study in nonhuman primates will evaluate an experimental drug's potential use as a gene therapy that could prevent people who have HIV from having to take daily antiviral drugs. In an earlier study, leronlimab completely prevented nonhuman primates from being infected with the monkey form of HIV. That result indicated that leronlimab held promise as a potential pre-exposure drug to prevent human infection from the virus that causes AIDS.
CytoDyn Inc. announced on April 12, 2022, the publication of a peer-reviewed research paper entitled "Suppression of human and simian immunodeficiency virus replication with the CCR5-specific antibody Leronlimab in two species" in the open-access journal PLOS Pathogens. 'Our results demonstrate that weekly, self-administered Leronlimab was safe, well-tolerated, and efficacious for long-term virologic suppression and should be included in the arsenal of safe, easily administered, longer-acting antiretroviral treatments for people living with HIV-1.'
On January 10, 2022, the Company announced that a research paper entitled "Leronlimab (PRO 140) activity against 4-class drug-resistant HIV-1 from Heavily Treatment Experienced Subjects" has been accepted, peer-reviewed, and is available as a journal pre-proof on ScienceDirect. Significant findings from the study and observations from the authors include: Leronlimab maintained full activity in the presence of extensive resistance to the four main antiviral classes; Leronlimab IC50 did not appear significantly altered by previous or current exposure to maraviroc; In vitro, leronlimab, and maraviroc have been reported to have synergistic activity, further corroborating the different mechanism of the two drugs despite the same CCR5 target; In vitro, susceptibility to leronlimab is not affected by extensive drug resistance and exposure to maraviroc; Leronlimab may have some advantages over maraviroc as a clinically valuable CCR5 antagonist, including lower toxicity, less drug-drug interaction issue, and less frequent dosing; Leronlimab can play a key role in subjects with very limited therapeutic options and CCR5-tropic virus.
Leronlimab Indication for Liver Fibrosis
CytoDyn is also conducting a Phase 2 clinical trial for Nonalcoholic steatohepatitis (NASH) to evaluate the effect of leronlimab on liver steatosis and fibrosis. There are currently no FDA-approved treatments for NASH, a leading cause of liver transplants. NASH is a chronic liver disease characterized histologically by hepatic inflammation and cell injury (hepatocellular ballooning) due to hepatic fat accumulation (steatosis) equal or superior to 5% of hepatocytes. Pre-clinical studies revealed a significant reduction in NAFLD and a reduction in liver fibrosis using leronlimab.
Leronlimab Use Against Triple-Negative Breast Cancer
CytoDyn Inc. announced on November 8, 2021, it had submitted to the U.S. FDA an application for Breakthrough Therapy designation for leronlimab as a potential treatment for mTNBC. Previously, the FDA granted CytoDyn Fast Track designation to explore potential indications using leronlimab to treat metastatic cancer. Health Canada authorized the emergency use of leronlimab on November 16, 2021, to treat a patient with metastatic triple-negative breast cancer.
Vyrologix Leronlimab Side Effects
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CytoDyn, Inc. Finacial News (OTCQB: CYDY)
February 29, 2024 - CytoDyn's CEO, Dr. Jacob Lalezari, stated, "We are excited that the clinical hold on leronlimab has been lifted by the FDA. CytoDyn is grateful for the FDA's guidance on our protocol, and we are excited to open a new chapter in the development of leronlimab as a therapy that provides clinical benefit by modulating chronic inflammation."
February 1, 2024 - CytoDyn Inc. announced that the Company has submitted its revised HIV clinical trial protocol to the FDA. The Company believes this submission will lead to the removal of the clinical hold currently in effect.
January 25, 2022 - The Board of Directors terminated the employment of Nader Z. Pourhassan, Ph.D., as President and CEO of the Company, and he is no longer a member of the Board of Directors.
December 22, 2021 - CytoDyn Inc. announced that the U.S. District Court for the District of Maryland had granted CytoDyn's previously-announced motion for a preliminary injunction against NSF International, Inc. and its subsidiary Amarex Clinical Research. The Company's complaint alleged that Amarex failed to perform its obligations under the master services agreement and work orders that governed the relationship between the parties. As a result, the Company suffered substantial damages.
May 31, 2021 - Form 10-k for the fiscal year ended May 31, 2021.
Vyrologix Leronlimab News For 2021 - 2022
April 22, 2022 - Senior author Dr. Otto Yang, a professor at the David Geffen School of Medicine at UCLA, stated, "Patients who improved were those who started with low CCR5 on their T cells, suggesting their immune system was less active than normal, and levels of CCR5 increased in people who improved. This leads to the new hypothesis that long COVID in some persons is related to the immune system being suppressed and not hyperactive and that while blocking its activity, the antibody can stabilize CCR5 expression on the cell surface leading to upregulation of other immune receptors or functions."
April 12, 2022 - Jonah Sacha, Ph.D., the lead study author, a CytoDyn scientific advisor, and an Oregon Health & Science University professor, stated, "To our knowledge, these data represent the longest administration of monoclonal antibody monotherapy for HIV in people to date."
March 30, 2022 - "CytoDyn is committed to FDA compliance," said Scott A. Kelly, M.D., Chief Medical Officer of CytoDyn, in a press statement. "We are evaluating our clinical programs and are working to resolve the issues underlying the clinical holds as soon as possible in close communication with the FDA. We will provide an update when we have additional information."
January 20, 2022 - The journal frontiers in Immunology published a review: Targeting CCR5 as a Component of an HIV-1 Therapeutic Strategy. Therapeutics targeting CCR5 generally involve gene-editing techniques including CRISPR, CCR5 blockade using antibodies or antagonists, or combinations of both. Here we review the efficacy of these approaches and discuss the potential of their use in the clinic as novel ART-independent therapies for HIV-1 infection.
January 10, 2022 - The Company issued a press release confirming Pharmacological Research became available online on January 6, 2022. CytoDyn previously hit a primary endpoint in a pivotal Phase 3 HIV trial with some HTE patients; over 20 patients remain in an extension arm study for up to 4 years.
January 5, 2022 - CytoDyn Inc. announced positive results from the 350 mg weekly dose of its Phase 2 NASH clinical trial. The trial was conducted in two parts. Part 1 compared a 700 mg weekly dose and placebo in a double-blind randomized manner, and Part 2 evaluated a 350 mg weekly dose as an open-label study compared to the same placebo blinded arm. The leronlimab 350 mg dose versus placebo comparison for the primary endpoint PDFF was statistically significant. Leronlimab, compared to placebo, also reached near significance for the secondary endpoint cT1. There were no significant differences in treatment-emergent adverse events between leronlimab and placebo groups.
December 21, 2021 - CytoDyn Inc. announced that it had received a positive response from the U.S. FDA to conduct a Phase 3, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of leronlimab in combination with standard of care for critically ill patients with COVID-19 pneumonia with the need for Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation. The submission of this protocol was previously announced on December 9, 2021.
December 9, 2021 - CytoDyn Inc. announced that it had submitted a Phase 3 trial with the U.S. FDA to evaluate the efficacy and safety of leronlimab in combination with standard of care for critically ill patients with COVID-19 pneumonia.
November 24, 2021 - CytoDyn Inc. reported data from its trial treating NASH (nonalcoholic steatohepatitis). Leronlimab open-label NASH results continue to show reductions in fat and fibrosis suggestive of a potential therapy not only for NAFLD (Non-Alcoholic Fatty Liver Deposit) but also in NASH. Fat decreases by proton density fat fraction PDFF up to 45% along with reductions in fibrosis up to 8% by CT1 were noted from baseline after just 14 weeks of treatment. In addition, reductions in fibrosis were seen in both severe and mild-moderate NASH cases.
November 19, 2021 - CytoDyn Inc. announced its research paper entitled "CCR5 receptor occupancy analysis reveals increased peripheral blood CCR5+CD4+ T cells following treatment with the anti-CCR5 antibody Leronlimab" which has been accepted by Frontiers in Immunology. Collectively, these results establish two RO calculation methods for longitudinal monitoring of anti-CCR5 therapeutic antibody blockade efficacy in both macaques and humans, demonstrating that CCR5+CD4+ T cell levels temporarily increase with Leronlimab treatment and facilitate future detailed investigations into the immunological impacts of CCR5 inhibition in multiple pathophysiological processes.
November 8, 2021 - We are grateful to have already received Fast Track designation for leronlimab for this indication (mTNBC) and congratulate Dr. Nitya Ray and his team for preparing the data analysis needed to file this BTD application so quickly," commented Nader Pourhassan, Ph.D.
November 3, 2021 - CytoDyn Inc. announced preliminary results from the first five patients treated with leronlimab in its Phase 2 trial for NASH (nonalcoholic steatohepatitis) open-label. These preliminary findings suggested that fatty deposits were lowered on all five patients by as much as 45% compared to the baseline measurement. In addition, fibrosis was also lowered by as much as 10% in 4 out of 5 patients compared to the baseline measurement. The Phase 2 trial for 90 patients is designed to test whether leronlimab may inhibit the devastating liver fibrosis associated with NASH.
November 3, 2021 - CytoDyn Inc. announced updated results from its current cancer study using leronlimab (in varying doses) to treat 28 patients with CCR5+ Metastatic Triple-Negative Breast Cancer ("mTNBC") who had failed at least two lines of previous therapy. This ongoing updated analysis is from 28 pooled patients, 16 from our Compassionate Use Study, ten from the Phase 1b/2 Study, and two from the Basket Study.
October 27, 2021 - CytoDyn Inc. announced today the U.S. FDA had accepted the revised "Rolling Review" timeline for the Company's upcoming resubmission of its Biologics License Application ("BLA") for leronlimab as a combination therapy for highly treatment-experienced HIV patients. The Company also announced that it expects the non-clinical and CMC sections of the BLA to be resubmitted to the FDA in November 2021, and, as previously disclosed, the clinical section of the BLA is anticipated to be completed and resubmitted during early 2022.
October 25, 2021 - CytoDyn Inc. announced the treatment of the first patient in its pivotal Phase 3 trial (CD16) in Brazil for critically ill COVID-19 patients. An interim analysis will be conducted 28 days following the enrollment of 127 patients.
October 7, 2021 - CytoDyn Inc. announced a study treating triple-negative breast cancer (TNBC) with leronlimab in a humanized TNBC xenograft model. The study is intended to determine the potential synergistic therapeutic efficacy of leronlimab in combination with immune checkpoint blockade (ICB) to attempt to raise the standard of care for breast cancer patients. This investigator-initiated study is led by Jangsoon Lee, Ph.D., assistant professor of Breast Medical Oncology Research at The University of Texas MD Anderson Cancer Center.
September 22, 2021 - CytoDyn Inc. announced that Brazil's regulatory authority, Agência Nacional de Vigilância Sanitária, has approved the start of a different Phase 3 CD16 clinical trial of leronlimab. The new clinical trial will focus on hospitalized COVID-19 patients in critical condition who require mechanical and invasive ventilation or Extracorporeal Membrane Oxygenation.
September 13, 2021 - CytoDyn Inc. (OTCQB: CYDY) announced Nader Pourhassan, Ph.D., President and CEO, and Scott Kelly, M.D., Chairman, and Chief Medical Officer, will provide a comprehensive business update at the upcoming Emerging Growth Conference. Previous investor presentations are available at this link.
September 9, 2021 - CytoDyn Inc. announced the treatment of the first patient in its pivotal Phase 3 COVID-19 trial in Brazil for patients with severe symptoms. An interim analysis will be conducted 28 days following the enrollment of 245 patients, 40% of the total number of patients enrolled in the trial.
August 26, 2021 - CytoDyn Inc. (OTCQB: CYDY) announced today Seenu Srinivasan, Ph.D., as Executive Director-CMC Regulatory Affairs.
August 25, 2021 - CytoDyn reveals data from its final mTNBC report with its flagship drug, leronlimab, in a video interview.
August 3, 2021 - CytoDyn Inc. announced that Brazil's regulatory authority Agência Nacional de Vigilância Sanitária)has approved the previously submitted clinical trial protocol to commence patient enrollment in its CD17 trial for severe COVID-19 patients. As a result, the Academic Research Organization Albert Einstein Israelite Hospital in Brazil will conduct the trial.
July 19, 2021 - CytoDyn Inc. announced strong preliminary results from its Phase 1b/2 trials and compassionate use with a total of 30 metastatic triple-negative breast cancer (mTNBC) patients. Patients in Phase 1b/2 were treated with leronlimab in combination with carboplatin.
May 19, 2021 - According to Pharmaceutical Technology, CytoDyn is set to submit the results from the Phase III CD12 clinical trial of Vyrologix (leronlimab-PRO 140), seeking potential regulatory approval for the drug to treat severe to critically ill patients with Covid-19.
May 3, 2021 - CytoDyn, a late-stage biotechnology company developing leronlimab (Vyrologix™ or PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced a comprehensive update three continuing extension studies with leronlimab as a treatment for HIV.
December 24, 2020 - CytoDyn Inc. announced the U.S. FDA guided the Company through adding an open-label extension to its Phase 3 trial ("CD12") and specific criteria for the continuation of for patients meeting the inclusion/exclusion criteria of CD12. Upon clearance, each CD12 participating clinical trial site will have the option of enrolling additional qualified patients, with all patients receiving leronlimab. In addition, treatment of qualified patients will continue until the trial's data is unblinded.
December 15, 2020 - CytoDyn Inc. announced it had reached full enrollment in its Phase 3 registrational trial for patients with severe-to-critical COVID-19. The 390-patient data will be analyzed in approximately 28 days, with expected results announced shortly after that.
November 23, 2020 - CytoDyn Inc., a biotechnology company developing Vyrologix™ (leronlimab-PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced today it had reached an enrollment of 293 patients in its Phase 3 trial for COVID-19 patients with severe-to-critical symptoms, thereby meeting the requested criteria for a second interim efficacy analysis by the Data Safety Monitoring Committee.
November 17, 2020 - Washington-based CytoDyn Inc. announced it had filed a protocol with the U.S. FDA for a Phase 2 clinical trial for leronlimab to treat COVID-19 patients suffering from long-hauler symptoms.
October 26, 2020 - CytoDyn Inc. announced the Medicines & Healthcare product Regulatory Agency of the U.K. government had cleared CytoDyn to file its Biologics License Application (BLA) leronlimab as a combination therapy for multi-drug resistance HIV patients in the U.K.
October 20, 2020 - CytoDyn Inc. announced recommendations from the Data Safety Monitoring Committee 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.
September 22, 2020 - CytoDyn's Phase 2 Study of Leronlimab for Mild-to-Moderate COVID-19 Selected for Oral Presentation at the Special isirv-AVG Virtual Conference on 'Therapeutics for COVID-19.'
July 21, 2020 - CytoDyn Inc. announced the results of the patient safety data from the Company's over-enrolled COVID-19 disease Phase 2 trial for treating mild-to-moderate indications. Just 5 patients out of 56 (about 9%) reported serious adverse events; none were related to leronlimab.
May 19, 2020 - CytoDyn Inc. announced it would coordinate with the NIH of Mexico and provide leronlimab for a trial for the severe - critical COVID-19 disease population in Mexico with the potential to collaborate on further collaboration CytoDyn COVID-19 trials. "The NIH of Mexico is committed to helping alleviate human suffering and mortality of Mexican citizens. The Metropolitan Area of the Valley of Mexico has a population of approximately 21.5 million people, and the contagious nature of COVID-19 is relentless," said Nader Pourhassan, Ph.D., President, and Chief Executive Officer of CytoDyn.
May 5, 2020 - CytoDyn Inc. announced a pre-print version of the manuscript had been made publicly available on posting with Research Square and MedRxiv describing the immunological mechanism by which leronlimab restores immune function and impacts disease in COVID-19 patients. As described in the pre-print, in a cohort of ten critically ill patients, after treatment with leronlimab, these critically ill patients experienced reversed hyperimmune activation and inflammation. In addition, they reversed immunosuppression, thereby facilitating a more effective immune response correlated with decreases in SARS-CoV-2 levels in the blood.
May 4, 2020 - CytoDyn Requests Compassionate Use from FDA for COVID-19 Patients Not Eligible for Participation in Two Ongoing Clinical Trials in the U.S. – CytoDyn Targets Enrollment Completion for its 75 Patient, Phase 2 Trial by the end of May.
April 7, 2020 - Novant Health is initiating patient enrollment in CytoDyn's Phase 2 randomized clinical trial for COVID-19 patients with mild-to-moderate infections. Novant Health is the first site in the southeastern United States to initiate this Phase 2 trial. And a Phase 2b/3 trial will be for severe and critically ill COVID-19 patients.
March 19, 2020 - CytoDyn Inc. announced today that two coronavirus patients were treated with the Company's investigational new drug, leronlimab. The treatment was administered at a leading medical center in the New York City area under an emergency Investigational New Drug (IND) recently granted by the U.S. Food and Drug Administration (FDA).
Vyrologix Leronlimab (Pro 140) Clinical Trials
Cytodyn's Vyrologix is being studied in 5 clinical trials. On August 2, 2021, Brazil authorized a phase 3 study. This pivotal Phase 3 trial for severe COVID-19 patients is conducted by Academic Research Organization ("ARO") Albert Einstein Israelite Hospital. This trial intends to provide Brazil's regulatory authority ANVISA (Agência Nacional de Vigilância Sanitária) with the requisite data to consider advancing the availability of leronlimab to Brazilians infected with COVID-19. The trial will be conducted in up to 35 clinical sites with 612 patients who are hospitalized and in need of oxygenation support.
On July 21, 2020, the Phase 2 study announced 34% (19 of 56 patients) were treated with leronlimab compared to 50% (14 of 28 patients) treated with placebo reported at least one adverse event. A total of 19 serious adverse events (SAEs) were reported during the study. Eleven SAEs were reported in 6 patients (6/28; 21.4%) receiving placebo compared to eight (8) SAEs in 5 patients (5/56; 8.9%) receiving leronlimab. None of the SAEs in the leronlimab arm were deemed related to study drug administration by the investigators. Of the 84 patients treated, one patient died 33 days after enrollment due to an event unrelated to leronlimab.
ClinicalTrials.gov Identifier: NCT04343651 - This is a Phase 2, two-arm, randomized, double-blind, placebo-controlled multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) in patients with mild-to-moderate symptoms of respiratory illness caused by coronavirus 2019 infection. Last updated on September 29, 2021.
CytoDyn is also conducting a Phase 2 clinical trial for NASH to evaluate the effect of leronlimab on liver steatosis and fibrosis. Pre-clinical studies revealed a significant reduction in NAFLD and a reduction in liver fibrosis using leronlimab.
To find out more about the clinical trials, please visit Cytodyn's clinical trial enrollment site.