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Introduction: Refractory status asthmaticus is a medical emergency with high risk for morbidity and mortality. For patients who fail standard ICU management, VV ECMO or inhaled anesthetics such as sevoflurane may be offered. There is growing numbers of case reports of “off label” or compassionate use of biologic agents such as anti-IGE omalizumab, anti-IL-5Ra benralizumab, and anti-TSLP tezepelumab. Prior to their use the indication, mechanism of action, risk/benefit, and pharmacodynamics of biologic therapies must be considered when used off label as rescue therapy. Here, we discuss a case of a patient with refractory status asthmaticus on VV ECMO who had improvement with off label use of omalizumab as rescue therapy. Description: A 49 year-old male with PMH of asthma and COPD with established T2 high phenotype presents to the emergency department for shortness of breath. The patient failed a limited trial of NIV requiring intubation. Due to difficulty with ventilation and high airway pressures the patient was placed on VV ECMO. Despite five days on ECMO, the patient had persistent bronchospasm that did not response to bronchodilators and transiently improved with magnesium boluses. Outpatient labs demonstrated T2 high inflammatory phenotype with eosinophilia and IGE over 800. Due to this and his refractory respiratory status, he was given a dose of outpatient omalizumab 600 mg via subcutaneous injection off label for compassionate use. At 48 hours the patient’s dynamic compliance quintupled from 27 mL/cm H2O to 140 mL/cm H2O and by four days post treatment the patient’s tidal volumes tripled from 150 mL to 450 mL. Nine days post treatment, the patient was de-cannulated from VV ECMO and extubated to supplemental oxygen. The patient was discharged home on room air five days later to follow up with pulmonology for his asthma. Discussion: Our patient showed improved ventilation at 48 hours and was able to be extubated and decannulated at day 9, this is consistent with the limited established literature and tracks with omalizumab’s onset of action of 7-8 days. Our case adds to the growing number of case reports describing the use of biologic agents in refractory status asthmaticus and is one of a handful of cases in a patient on VV ECMO.