Cytodyn Inc (CYDY)

[morokoy]

https://www.sciencedirect.com/science/article/pii/S2589909021000174?dgcid=rss_sd_all

3. Case DESCRIPTION
The male subject was admitted to a London teaching hospital in the United Kingdom with confirmed nasopharyngeal swabs positive for SARS-CoV-2 infection by reverse transcriptase polymerase chain reaction (RT–PCR). He is of mixed race in his late 50’s with critical COVID-19. Other pertinent characteristics include a BMI of 37 kg/m2, prior smoker, and well-controlled hypertension. Following a positive test for SARS-CoV-2 infection, the subject was admitted to hospital with dyspnoea and pyrexia (Day 0). The subject received several investigational treatments prior to treatment with leronlimab. Upon admission, the subject was treated with dexamethasone for 10 days. Remdesivir was initiated on Day 1; a plasma exchange was administered on Day 4 for 10 days. Other drug interventions included intravenous antibiotics. The subject’s condition continued to deteriorate, and ECMO was initiated on Day 19. Four doses of leronlimab (700 mg), obtained from CytoDyn (CytoDyn inc. WA, USA) through an Emergency Investigational New Drug (EIND) application, were administered on Days 79, 86 and 93 and 100 post diagnosis. The subject responded extremely rapidly and was weaned off ECMO between Days 82 to 84, and he was discharged from the ECMO intensive care unit on Day 91. No adverse safety issues were identified with the administration of leronlimab in this subject. Oxygen therapy and intravenous antibiotics for ventilator-associated pneumonia were administered post weaning off ECMO. At last follow up the subject’s condition continues to improve and he is undergoing rehabilitation.

4. Discussion
Recent data suggest that severely dysregulated host immune responses to SAR-CoV-2, referred to as ‘cytokine storm’, may predominately mediate the morbidity and mortality of severe-to-critical COVID-19[13, 22, 23]. Cytokine storm primarily leads to lung inflammation causing acute respiratory distress syndrome (ARDS), but cytokine storm can also result in severe extrapulmonary manifestations, including thrombotic complications, myocardial dysfunction, and liver and kidney injury[24]. CCR5-expressing proinflammatory immune cells such as activated T-cells and macrophages are thought to play a key role in the cytokine storm response to COVID-19, suggesting that drug interventions that target the CCR5 system may represent a promising approach to treating COVID-19[13].

Leronlimab is a C-C chemokine receptor type 5 (CCR5)-specific humanised IgG4 monoclonal antibody. In a Phase 2, placebo-controlled, randomized clinical trial in subjects with mild-to-moderate COVID-19 leronlimab was shown to provide clinical benefit, primarily in subjects with more severe disease. A number of recent case series have demonstrated that treatment with leronlimab restores immune function and achieves clinical improvement in people with critical COVID-19. Taken together therapeutic interventions that target the chemokine receptor–ligand system may be an effective approach to treating COVID-19 because chemotaxis and trafficking of CCR5 expressing proinflammatory immune cells are thought to play an important role in this process. Importantly the long-term safety of leronlimab is already well established in the treatment of HIV[[17], [18], [19]].

This case is of particular interest because to the best of our knowledge this subject received ECMO for the longest period of any person in the United Kingdom with COVID-19 (66 days). He received his first dose of leronlimab on Days 79 after diagnosis and was successfully weaned off ECMO between Days 82 to 84 and discharged from the ECMO intensive care unit on Day 91. Considering the length of time this subject was on ECMO and the speed of the subject’s response to leronlimab we believe that this case adds critical insight to the growing body of evidence for leronlimab in treatment of critical COVID-19.