Humanigen (Nasdaq: HGEN), a clinical-stage biopharmaceutical company focused on preventing and treating an immune hyper-response called ‘cytokine storm’
Cytokine storm (CS) is a severe immune reaction in which the body releases a high level of cytokines in the blood in a short time frame, that can lead to multiple organ failure and death. Cytokine storm occurs in many medical conditions including graft vs host disease, CAR-T toxicity, adult respiratory distress syndrome, and can be triggered in severe cases of COVID-19 . As the scientific and medical community learned about cytokine storm in COVID-19, lenzilumab was repurposed from development for CAR-T to COVID-19 patients. Repurposing drugs normally takes years, with substantial attrition rates, and a slow methodical pace of development. The urgency of the the pandemic accelerated efforts to find therapies to address CS in patients hospitalized with COVID-19 pneumonia. Humanigen quickly sought to investigate lenzilumab as a breakthrough treatment for COVID-19 and worked with clinicians at the Mayo clinic using individual compassionate use IND's to confirm beneficial effects from March-June 2020. Humanigen sought and received FDA approval for an IND for compassionate use in early April 2020 before receiving FDA approval for its Phase 3 in late April. The first patient in the 520-patient Phase 3 study was dosed in May 2020 and the last was enrolled in January 2021. The Phase 3 "LIVE-AIR" study demonstrated patients benefit from treatment with lenzilumab by improving the likelihood of survival without ventilation in the overall treatment population by 54%. In the subset of patients who responded best to treatment (patients age <85 with baseline CRP<150) survival improved by 2.2-fold.
Lenzilumab is a first-in-class recombinant monoclonal antibody targeting human GM-CSF. It is the only anti-GM-CSF therapy proven in a Phase 3 trial to effectively treat hypoxic hospitalized patients with COVID-19 pneumonia. Because lenzilumab neutralizes GM-CSF to treat the cytokine storm resulting from coronavirus infection, it is not subject to failures associated with antibodies that target the virus and have proven less effective (and in some instances completely ineffective) against new variants. Thus, lenzilumab can be used to treat patients who are not vaccinated, partially vaccinated, have inadequate vaccination through compromised immune response, and with any coronavirus variant.
Mayo Clinic completed a case cohort study in June 2020 demonstrating lenzilumab was safe and associated with faster improvement in clinical outcomes, including oxygenation, and greater reductions in inflammatory markers compared with a matched control of patients hospitalized with severe COVID-19 pneumonia. https://www.mayoclinicproceedings.org/article/S0025-6196(20)30989-7/fulltext NIH evaluated around 400 therapeutics and selected lenzilumab as one of less than 30 drugs/biologics placed under evaluation for "Accelerating COVID-19 Therapeutic Interventions and Vaccines". https://www.nih.gov/research-training/medical-research-initiatives/activ/covid-19-therapeutics-prioritized-testing-clinical-trials#activ6 https://directorsblog.nih.gov/2021/02/16/activ-update-making-major-strides-in-covid-19-therapeutic-development/ In Nov. 2020 lenzilumab chosen as one of 14 promising therapeutics identified by BARDA for its medical countermeasures portfolio. https://www.medicalcountermeasures.gov/newsroom/2020/humanigen/ https://www.medicalcountermeasures.gov/app/barda/coronavirus/COVID19.aspx?filter=therapeutic March 2021, Humanigen reported top-line results of a 520-patient Phase 3 study begun in May 2020. https://www.medrxiv.org/content/10.1101/2021.05.01.21256470v1.full.pdf Based on Humanigen's Phase 3 results, NIH advanced ACTIV-5/BET-B study of lenzilumab from Phase 2 to Phase 2/3, increased trial size from 200 to 400, and aligned the primary endpoint to the patient population for which the greatest benefit was demonstrated. https://s28.q4cdn.com/539885110/files/doc_news/NIH-Advances-ACTIV-5BET-B-Trial-Evaluating-Lenzilumab-from-a-Phase-2-Exploratory-Study-to-a-Phase-23-Study-for-the-Treatment-of-COVID-CML3P.pdf