Clinical and Economic Benefits of Lenzilumab Plus Standard of Care Compared with Standard of Care Alone for the Treatment of Hospitalized Patients with Coronavirus Disease 19 (COVID-19) from the Perspective of National Health Service England

References

• Sarkodie SA, Owusu PA. Global assessment of environment, health and economic impact of the novel coronavirus (COVID-19). Environ Dev Sustain. 2020;5–11. doi:10.1007/s10668-10020-00801-10662
   Web of Science ®Google Scholar
• Kaye AD, Okeagu CN, Pham AD, et al. Economic impact of COVID-19 pandemic on healthcare facilities and systems: international perspectives. Best Pract Res Clin Anaesthesiol. 2021;35(3):293–306. doi:10.1016/j.bpa.2020.11.009
   PubMed Web of Science ®Google Scholar
• Nicola M, Alsafi Z, Sohrabi C, et al. The socio-economic implications of the coronavirus pandemic (COVID-19): a review. Int J Surg. 2020;78:185–193. doi:10.1016/j.ijsu.2020.04.018
   PubMed Web of Science ®Google Scholar
• World Health Organization. WHO Coronavirus (COVID-19) Dashboard; [ updated January 25, 2022]. Available from: https://covid19.who.int/. Accessed January 25, 2022.
   Google Scholar
• Government of the United Kingdom. Cases in United Kingdom; [ updated January 25, 2022]. Available from: https://coronavirus.data.gov.uk/details/cases. Accessed January 25, 2022.
   Google Scholar
• Government of the United Kingdom. Deaths in United Kingdom; [ updated January 25, 2022]. Available from: https://coronavirus.data.gov.uk/details/deaths. Accessed January 25, 2022.
   Google Scholar
• Government of the United Kingdom. Patients admitted to hospital in United Kingdom; [ updated January 25, 2022]. Available from: https://coronavirus.data.gov.uk/details/healthcare. Accessed January 25, 2022.
   Google Scholar
• Docherty AB, Harrison EM, Green CA, et al. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO clinical characterisation Protocol: prospective observational cohort study. BMJ. 2020;369:m1985. doi:10.1136/bmj.m1985
   PubMed Web of Science ®Google Scholar
• Government of the United Kingdom. Vaccinations in United Kingdom; [ updated January 25, 2022]. Available from: https://coronavirus.data.gov.uk/details/vaccinations. Accessed January 25, 2022.
   Google Scholar
• Thakur V, Ratho RK. OMICRON (B.1.1.529): a new SARS-CoV-2 variant of concern mounting worldwide fear. J Med Virol. 2021. doi:10.1002/jmv.27541
   PubMed Web of Science ®Google Scholar
• United Kingdom Health Security Agency. SARS-CoV-2 variants of concern and variants under investigation in England: technical briefing updated on hospitalisation and vaccine effectiveness for Omicron VOC-21-NOV-01 (B.1.1.529); 2021. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1044481/Technical-Briefing-31-Dec-2021-Omicron_severity_update.pdf. Accessed January 5, 2022.
   Google Scholar
• Callaway E, Ledford A. How bad is Omicron? What scientists know so far. Nature. 2021;600(7888):197–199. doi:10.1038/d41586-021-03614-z
   PubMed Web of Science ®Google Scholar
• Government of the United Kingdom. COVID-19 NHS daily situation report; [ updated January 25, 2022]. Available from: https://coronavirus.data.gov.uk/details/healthcare?areaType=nation&areaName=England. Accessed January 25, 2022.
   Google Scholar
• Rae M, Claxton G, Kurani N, McDermott D, Cox C Potential costs of COVID-19 treatment for people with employer coverage; 2021. Available from: https://www.healthsystemtracker.org/brief/potential-costs-of-coronavirus-treatment-for-people-with-employer-coverage/. Accessed July 6, 2021.
   Google Scholar
• Di Fusco M, Shea KM, Lin J, et al. Health outcomes and economic burden of hospitalized COVID-19 patients in the United States. J Med Econ. 2021;24(1):308–317. doi:10.1080/13696998.2021.1886109
   PubMed Web of Science ®Google Scholar
• Czernichow S, Bain SC, Capehorn M, et al. Costs of the COVID-19 pandemic associated with obesity in Europe: a health-care cost model. Clin Obes. 2021;11(2):e12442. doi:10.1111/cob.12442
   PubMed Web of Science ®Google Scholar
• Sheinson D, Dang J, Shah A, Meng Y, Elsea D, Kowal S. A cost-effectiveness framework for COVID-19 treatments for hospitalized patients in the United States. Adv Ther. 2021;38(4):1811–1831. doi:10.1007/s12325-021-01654-5
   PubMed Web of Science ®Google Scholar
• Goletti D, Cantini F. Baricitinib therapy in Covid-19 pneumonia - An unmet need fulfilled. N Engl J Med. 2021;384(9):867–869. doi:10.1056/NEJMe2034982
   PubMed Web of Science ®Google Scholar
• Liu CH, Lu CH, Wong SH, Lin LT. Update on antiviral strategies against COVID-19: unmet needs and prospects. Front Immunol. 2020;11(3845):616595. doi:10.3389/fimmu.2020.616595
   PubMed Web of Science ®Google Scholar
• Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 cytokine storm; what we know so far. Front Immunol. 2020;11:1446. doi:10.3389/fimmu.2020.01446
   PubMed Web of Science ®Google Scholar
• Temesgen Z, Burger CD, Baker J, et al. Lenzilumab in hospitalised patients with COVID-19 pneumonia (LIVE-AIR): a phase 3, randomised, placebo-controlled trial. Lancet Respir Med. 2021;10(3):237–246. doi:10.1016/S2213-2600(21)00494-X
   PubMed Web of Science ®Google Scholar
• Hamilton JA. GM-CSF in inflammation. J Exp Med. 2020;217(1):e20190945. doi:10.1084/jem.20190945
   PubMed Web of Science ®Google Scholar
• Lang FM, Lee KM, Teijaro JR, Becher B, Hamilton JA. GM-CSF-based treatments in COVID-19: reconciling opposing therapeutic approaches. Nat Rev Immunol. 2020;20(8):507–514. doi:10.1038/s41577-020-0357-7
   PubMed Web of Science ®Google Scholar
• Sproston NR, Ashworth JJ. Role of C-reactive protein at sites of inflammation and infection. Front Immunol. 2018;9:754. doi:10.3389/fimmu.2018.00754
   PubMed Web of Science ®Google Scholar
• Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124(2):188–195. doi:10.1182/blood-2014-05-552729
   PubMed Web of Science ®Google Scholar
• Hu B, Guo H, Zhou P, Shi ZL. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. 2021;19(3):141–154. doi:10.1038/s41579-020-00459-7
   PubMed Web of Science ®Google Scholar
• Zhou Y, Fu B, Zheng X, et al. Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients. Natl Sci Rev. 2020;7(6):998–1002. doi:10.1093/nsr/nwaa041
   PubMed Web of Science ®Google Scholar
• Thwaites RS, Sanchez Sevilla Uruchurtu A, Siggins MK, et al. Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19. Sci Immunol. 2021;6(57):57. doi:10.1126/sciimmunol.abg9873
   Web of Science ®Google Scholar
• Kox M, Waalders NJB, Kooistra EJ, Gerretsen J, Pickkers P. Cytokine levels in critically ill patients with COVID-19 and other conditions. JAMA. 2020;324(15):1565–1567. doi:10.1001/jama.2020.17052
   PubMed Web of Science ®Google Scholar
• Hodges G, Pallisgaard J, Schjerning Olsen AM, et al. Association between biomarkers and COVID-19 severity and mortality: a nationwide Danish cohort study. BMJ Open. 2020;10(12):e041295. doi:10.1136/bmjopen-2020-041295
   PubMed Web of Science ®Google Scholar
• Mueller AA, Tamura T, Crowley CP, et al. Inflammatory biomarker trends predict respiratory decline in COVID-19 patients. Cell Rep Med. 2020;1(8):100144. doi:10.1016/j.xcrm.2020.100144
   PubMedGoogle Scholar
• Smilowitz NR, Kunichoff D, Garshick M, et al. C-reactive protein and clinical outcomes in patients with COVID-19. Eur Heart J. 2021;42(23):2270–2279. doi:10.1093/eurheartj/ehaa1103
   PubMed Web of Science ®Google Scholar
• Lavillegrand JR, Garnier M, Spaeth A, et al. Elevated plasma IL-6 and CRP levels are associated with adverse clinical outcomes and death in critically ill SARS-CoV-2 patients: inflammatory response of SARS-CoV-2 patients. Ann Intensive Care. 2021;11(1):9. doi:10.1186/s13613-020-00798-x
   PubMed Web of Science ®Google Scholar
• Petrilli CM, Jones SA, Yang J, et al. Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study. BMJ. 2020;369:m1966. doi:10.1136/bmj.m1966
   PubMed Web of Science ®Google Scholar
• Luo X, Zhou W, Yan X, et al. Prognostic value of C-reactive protein in patients with Coronavirus 2019. Clin Infect Dis. 2020;71(16):2174–2179. doi:10.1093/cid/ciaa641
   PubMed Web of Science ®Google Scholar
• Ali N. Elevated level of C-reactive protein may be an early marker to predict risk for severity of COVID-19. J Med Virol. 2020;92(11):2409–2411. doi:10.1002/jmv.26097
   PubMed Web of Science ®Google Scholar
• European Commission. European Health Union: commission establishes portfolio of 10 most promising treatments for COVID-19; 2021. Available from: https://ec.europa.eu/commission/presscorner/detail/en/IP_21_5366. Accessed November 2, 2021.
   Google Scholar
• Temesgen Z, Burger CD, Baker J, et al. Lenzilumab efficacy and safety in newly hospitalized Covid-19 subjects: results from the live-air phase 3 randomized double-blind placebo-controlled trial. medRxiv. 2021. doi:10.1101/2021.05.01.21256470
   PubMedGoogle Scholar
• Temesgen Z, Kelley CF, Cerasoli F, et al. Early lenzilumab treatment of COVID-19 patients using c-reactive protein as a biomarker improves efficacy: results from the phase 3 ‘LIVE-AIR’ trial. medRxiv. 2022. doi:10.1101/2021.12.30.21267140
   Google Scholar
• Humanigen. Lenzilumab treatment may provide enhanced likelihood of survival without ventilation in Hospitalized Black and African-American COVID-19 patients; 2021. Available from: https://ir.humanigen.com/English/news/news-details/2021/Lenzilumab-TreatmentMay-Provide-Enhanced-Likelihood-of-Survival-Without-Ventilation-in-Hospitalized-Black-and-African-American-COVID-19-Patients/default.aspx. Accessed September 24, 2021.
   Google Scholar
• Office for National Statistics. Updating ethnic contrasts in deaths involving the coronavirus (COVID-19), England: 24 January 2020 to 31 March 2021; 2021. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/articles/updatingethniccontrastsindeathsinvolvingthecoronaviruscovid19englandandwales/24january2020to31march2021. Accessed October 4, 2021.
   Google Scholar
• Kadambari S, Vanderslott S. Lessons about COVID-19 vaccine hesitancy among minority ethnic people in the UK. Lancet Infect Dis. 2021;21(9):1204–1206. doi:10.1016/S1473-3099(21)00404-7
   PubMed Web of Science ®Google Scholar
• Razai MS, Kankam HKN, Majeed A, Esmail A, Williams DR. Mitigating ethnic disparities in covid-19 and beyond. BMJ. 2021;372:m4921. doi:10.1136/bmj.m4921
   PubMed Web of Science ®Google Scholar
• Kilcoyne A, Jordan E, Zhou A, et al. Clinical and economic benefits of lenzilumab plus standard of care compared with standard of care alone for the treatment of hospitalized patients with COVID-19 in the United States from the hospital perspective. J Med Econ. 2022:1–21. doi:10.1080/13696998.13692022.12030148.
   Web of Science ®Google Scholar
• Humanigen. ACTIV-5/Big Effect Trial (BET-B) for the Treatment of COVID-19; 2020 [ updated December 1, 2021]. NLM identifier: NCT04583969. Available from: https://www.clinicaltrials.gov/ct2/show/NCT04583969. Accessed January 11, 2022.
   Google Scholar
• Humanigen. Humanigen announces target enrollment in Phase 2/3 ACTIV-5/BET-B trial of lenzilumab for the treatment of COVID-19 has been achieved; 2022. Available from: https://ir.humanigen.com/English/news/news-details/2022/Humanigen-Announces-Target-Enrollment-in-Phase-23-ACTIV-5BET-B-Trial-of-Lenzilumab-for-the-Treatment-of-COVID-19-has-Been-Achieved/default.aspx. Accessed January 6, 2022.
   Google Scholar
• Arch BN, Kovacs D, Scott JT, et al. Evaluation of the effectiveness of remdesivir in treating severe COVID-19 using data from the ISARIC WHO Clinical characterisation protocol UK: a prospective, national cohort study. medRxiv. 2021. doi:10.1101/2021.06.18.21259072
   Google Scholar
• Humanigen. Market research with chest physicians, infection control and intensive care specialists (N=82). Data on file;. 2021.
   Google Scholar
• Humanigen. Additional data analyses for LIVE-AIR Phase 3 randomized double-blind placebo-controlled trial. Data on file;. 2021.
   Google Scholar
• National Health Service Digital. Hospital admitted patient care and adult critical care activity 2020–21; 2021. Available from: https://digital.nhs.uk/data-and-information/publications/statistical/hospital-admitted-patient-care-activity/2020-21. Accessed January 10, 2022.
   Google Scholar
• Office for National Statistics. Consumer price inflation time series; CPI INDEX 06: HEALTH; [ Updated October 2021]. Available from: https://www.ons.gov.uk/economy/inflationandpriceindices/datasets/consumerpriceindices. Accessed January 12, 2022.
   Google Scholar
• Humanigen. Lenzilumab drug cost. Data on file; 2022.
   Google Scholar
• Specialist Pharmacy Service. Remdesivir; 2020. Available from: https://www.sps.nhs.uk/medicines/remdesivir/. Accessed July 15, 2021.
   Google Scholar
• National Health Service. Interim clinical commissioning policy: remdesivir for patients hospitalised with COVID-19 (adults and children 12 years and older); 2021. Available from: https://www.england.nhs.uk/coronavirus/wp-content/uploads/sites/52/2020/07/C1322-interim-cc-policy-remdesivir-for-people-hospitalised-with-covid-19-v3.pdf. Accessed July 15, 2021.
   Google Scholar
• Burcombe R, Chan S, Simcock R, Samanta K, Percival F, Barrett-Lee P. Subcutaneous trastuzumab (Herceptin): a UK time and motion study in comparison with Intravenous formulation for the treatment of patients with HER2-positive early breast cancer. Adv Breast Cancer Res. 2013;02(04):133–140. doi:10.4236/abcr.2013.24022
   Google Scholar
• National Institute for Health and Care Excellence. Ravulizumab for treating atypical haemolytic uraemic syndrome (aHUS) [ID1530] committee papers; 2020. Available from: https://www.nice.org.uk/guidance/ta710/documents/committee-papers-2. Accessed July 20, 2021.
   Google Scholar
• Lambert A. USP 797: a breakdown of low, medium and high compounding risks. 2021. https://www.wolterskluwer.com/en/expert-insights/usp-797-a-breakdown-of-low-medium-and-high-risks. Available from Accessed, 2022.
   Google Scholar
• Hazard D, Kaier K, von Cube M, et al. Joint analysis of duration of ventilation, length of intensive care, and mortality of COVID-19 patients: a multistate approach. BMC Med Res Methodol. 2020;20(1):206. doi:10.1186/s12874-020-01082-z
   PubMed Web of Science ®Google Scholar
• Manson JJ, Crooks C, Naja M, et al. COVID-19-associated hyperinflammation and escalation of patient care: a retrospective longitudinal cohort study. Lancet Rheumatol. 2020;2(10):e594–e602. doi:10.1016/S2665-9913(20)30275-7
   PubMedGoogle Scholar
• Holmes EAF, Harris SD, Hughes A, Craine N, Hughes DA. Cost-effectiveness analysis of the use of point-of-care c-reactive protein testing to reduce antibiotic prescribing in primary care. Antibiotics. 2018;7(4):106. doi:10.3390/antibiotics7040106
   Web of Science ®Google Scholar
• Chastain DB, Osae SP, Henao-Martinez AF, Franco-Paredes C, Chastain JS, Young HN. Racial disproportionality in Covid clinical trials. N Engl J Med. 2020;383(9):e59.
   PubMed Web of Science ®Google Scholar
• Vekaria B, Overton C, Wisniowski A, et al. Hospital length of stay for COVID-19 patients: data-driven methods for forward planning. BMC Infect Dis. 2021;21(1):700. doi:10.1186/s12879-021-06371-6
   PubMed Web of Science ®Google Scholar
• Imperial College COVID-19 Response Team. Report 50: hospitalisation risk of Omicron cases in England; 2021. Available from: https://www.imperial.ac.uk/media/imperial-college/medicine/mrc-gida/2021-12-22-COVID19-Report-50.pdf. Accessed January 17, 2022.
   Google Scholar
• Humanigen. FDA has declined Humanigen’s Emergency Use Authorization (EUA) request for lenzilumab in hospitalized COVID-19 patients; 2021. Available from: https://ir.humanigen.com/English/news/news-details/2021/FDA-has-declined-Humanigens-Emergency-Use-Authorization-EUA-Request-for-Lenzilumab-in-Hospitalized-COVID-19-Patients/default.aspx. Accessed September 24, 2021.
   Google Scholar
• Government of the United Kingdom. Daily update: UK summary; [ Updated January 25, 2022]. Available from: https://coronavirus.data.gov.uk/. Accessed January 25, 2022.
   Google Scholar
• National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. [ updated December 16, 2021]. Available from: https://www.nice.org.uk/guidance/ng191/resources/covid19-rapid-guideline-managing-covid19-pdf-51035553326. Accessed January 6, 2022.
   Google Scholar
• Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: a clinical-therapeutic staging proposal. J Heart Lung Transplant. 2020;39(5):405–407. doi:10.1016/j.healun.2020.03.012
   PubMed Web of Science ®Google Scholar
• Horby P, Lim WS; Recovery Collaborative Group. Supplemental to: dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693–704.
   PubMed Web of Science ®Google Scholar
• Food and Drug Administration. Frequently asked questions on the emergency use authorization for Actemra (Tocilizumab) for treatment of COVID-19; 2021. Available from: https://www.fda.gov/media/150345/download#:~:text=The%20EUA%20authorizes%20Actemra%20(tocilizumab,oxygen%2C%20non%2Dinvasive%20or%20invasive. Accessed October 4, 2021.
   Google Scholar