Leronlimab (codenamed PRO 140) is a humanized monoclonal antibody targeted against the CCR5 receptor found on T lymphocytes of the human immune system. It is being investigated as a potential therapy in the treatment of triple negative breast cancer and HIV infection. The United States Food and Drug Administration has designated PRO 140 for fast-track approval. It was investigated as a treatment for COVID-19 but found to be ineffective for that purpose.
Development PRO 140 is being developed by Cytodyn Inc. In May 2007, results from the phase I clinical trial of the drug demonstrated "potent, rapid, prolonged, dose-dependent, highly significant antiviral activity" for PRO 140. Participants in the highest-dosing group received 5 milligrams per kilogram and showed an average viral load decrease of -1.83 log10. On average, reductions of greater than -1 log10 per milliliter were maintained for between two and three weeks, from only a single dose of the drug. The largest individual HIV RNA reductions ranged up to -2.5 log10 among patients receiving both the 2 and 5 mg/kg doses. In February 2018, Cytodyn Inc reported that the primary endpoint was achieved in the PRO 140 pivotal combination therapy trial in HIV infection and will continue for an additional 24 weeks (end of August 2018) with PRO 140 weekly subcutaneous injections and optimized ART. The report discloses that a single 350mg subcutaneous injection of PRO 140 resulted in a HIV-1 RNA viral load reduction greater than 0.5log or 68% within one week compared with those who received a placebo. The primary efficacy endpoint results were presented at ASM Microbe 2018. In the pivotal trial of Leronlimab in combination with standard anti-retroviral therapies in HIV-infected treatment-experienced patients, 81% of patients completing trial achieved HIV viral load suppression of < 50 cp/mL. Recent approved drugs for this population range from 43% after 24 weeks to 45% after 48 weeks with viral load suppression of < 50 cp/mL. In March 2019 CytoDyn filed with the US FDA the first part of the BLA for leronlimab (PRO140) as a combination therapy with HAART in HIV. In December 2019, the company affirmed plans to complete the BLA in January 2020 with potential FDA approval in 2Q'20. CytoDyn is also conducting an investigative monotherapy trial of leronlimab (PRO140) for HIV. If successful, once per week self-administered leronlimab would represent a paradigm shift in treatment of HIV. CytoDyn is also currently investigating the use of Leronlimab (PRO140) in various solid tumors. On February 18, 2019, CytoDyn announced it will begin 8 pre-clinical studies on melanoma, pancreatic, breast, prostate, colon, lung, liver, and stomach cancer. On November 23, 2018, CytoDyn received FDA approval of its IND submission and allowed to initiate a Phase 1b/2 clinical trial for metastatic triple-negative breast cancer (mTNBC) patients. In May 2019, the U.S. Food and Drug Administration (FDA) granted Fast Track Designation for Leronlimab (PRO 140) for use in combination with carboplatin for the treatment of patients with CCR5-positive mTNBC. In July 2019, CytoDyn announced the dosing of first mTNBC patient under compassionate use. Simultaneously, the phase 1b/2 trial for treatment-naïve mTNBC patients is active and anticipates top line data in 2020. If successful, the data from treatment-naïve mTNBC patients could serve as the basis for potentially seeking accelerated US FDA approval. On November 11, 2019, CytoDyn reported that the first TNBC patient injected under its naïve protocol (not previously treated for triple-negative breast cancer) demonstrated significantly reduced levels of circulating tumor cells (CTCs) and decreased tumor size at two-week and five-week observation intervals compared to baseline observations. CTCs are a potential surrogate endpoint in oncology trials, with reduced levels suggesting long-term clinical benefit. Recent published studies demonstrated Leronlimab reduced the number and size of new human breast cancer metastasis in a mouse model and reduced the size of established metastasis thereby extending survival. In May 2019, CytoDyn also initiated a pre-clinical study of Leronlimab (PRO 140) to prevent nonalcoholic steatohepatitis with The Cleveland Clinic. In November, the company reported positive results. On December 15, 2020, CytoDyn reached full enrollment in its Phase 3 registrational trial for patients with severe-to-critical COVID-19. The results showed a reduction in the primary end point of mortality of 24 percent after 28 days compared to the current standard of care. While not statistically significant, it is widely believed that only allowing two doses on day zero and day seven rather than the four doses that the company requested prevented the trial from meeting its primary end point. The half life of leronlimab is about 10 days, meaning that the effect of the drug would have been much less at day 28. Statistical analysis of the critically ill population (hospitalized patients receiving invasive mechanical ventilation (IMV) or ECMO), revealed that when leronlimab was added to standard of care ("SoC"), leronlimab decreased mortality at 14 days by 82% (p=.0233, N=62). Patients who received leronlimab were over five times more likely to be alive at day 14 than those who received SoC only. Length in hospital stay also decreased by 5.5 days in the critically ill population (N=62, p=.005).
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