DailyMed Label: GOHIBIC

DailyMed Label: GOHIBIC

2023

DailyMed Prescription

GOHIBIC

vilobelimab

InflaRx GmbH

NDC: 83000-110

NDC: 83000-110

NDC: 83000-110

NDC: 83000-110

NDC: 83000-110

NDC: 83000-110

NDC: 83000-110

Vilobelimab is a chimeric human/mouse immunoglobulin G4 (IgG4) antibody consisting of mouse anti-human complement factor 5a (C5a) monoclonal binding sites (variable regions of heavy and light chain regions), and human gamma 4 heavy chain and kappa light chain constant regions. GOHIBIC is composed of 1,328 amino acids, and the glycosylated intact protein has an approximate molecular weight of 149 kDa produced in Chinese Hamster Ovary (CHO) cell line genetically engineered using ribonucleic acid transfer through a retro-vector system. GOHIBIC (vilobelimab) injection is a clear to slightly opalescent, colorless solution for intravenous infusion after further dilution. GOHIBIC is provided in single-dose vials at a concentration of 200 mg/20 mL (10 mg/mL). Each mL also contains dibasic sodium phosphate (0.97 mg), monobasic sodium phosphate (0.4 mg), polysorbate 80 (0.5 mg), sodium chloride (8.8 mg), and Water for Injection. The pH is 6.6 – 7.3.

The recommended dosage of GOHIBIC for the treatment of adults with COVID-19 is 800 mg administered by intravenous infusion after dilution [see Dosage and Administration (2.2) ] for a maximum of 6 (six) doses over the treatment period as described below. Treatment should be started within 48 hours of intubation (Day 1) followed by administration on Days 2, 4, 8, 15 and 22 as long as the patient is hospitalized (even if discharged from ICU). Preparation Using aseptic technique, dilute and prepare GOHIBIC for intravenous infusion before administration. For the recommended dose of 800 mg GOHIBIC, dilute 80 mL of GOHIBIC in 170 mL of 0.9% Sodium Chloride at room temperature. Use a 250 mL infusion bag of 0.9% Sodium Chloride solution USP and the follow steps below: Withdraw 80 mL of 0.9% Sodium Chloride solution USP from the infusion bag and discard. Withdraw the 80 mL of GOHIBIC from the vials and add slowly to the 0.9% Sodium Chloride solution USP infusion bag to a final concentration of 3.2 mg/mL. To mix the solution, gently invert the bag to avoid foaming. Storage of Diluted GOHIBIC Diluted GOHIBIC must be used within 4 hours when stored at room temperature 20°C to 25°C (68°F to 77°F). Diluted GOHIBIC stored under refrigeration at 2°C to 8°C (36°F to 46°F) must be used within 24 hours. After removal of diluted GOHIBIC from the refrigerator stored at 2°C to 8°C (36°F to 46°F), it must be left to acclimatize to room temperature prior to administration. Administration Visually inspect for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if discoloration or visible particles are present. Administer diluted GOHIBIC via intravenous infusion over 30 - 60 minutes. Avoid concomitant administration of GOHIBIC with other drugs in the same intravenous line.

Injection: 200 mg/20 mL (10 mg/mL) clear to slightly opalescent, colorless solution in a single-dose vial.

No contraindications have been identified based on the limited available data for the emergency use of GOHIBIC under this EUA.

There are limited clinical data available for GOHIBIC. Serious and unexpected adverse events (AEs) may occur that have not been previously reported with GOHIBIC use. Serious infections due to bacterial, fungal, and viral pathogens have been reported in patients with COVID-19 receiving GOHIBIC. In patients with COVID-19, monitor for signs and symptoms of new infections during and after treatment with GOHIBIC. There is limited information regarding the use of GOHIBIC in patients with COVID-19 and concomitant active serious infections. The risks and benefits of treatment with GOHIBIC in COVID-19 patients with other concurrent infections should be considered [see Adverse Reactions (6) ] . Hypersensitivity reactions have been observed with GOHIBIC. If a severe hypersensitivity reaction occurs, administration of GOHIBIC should be discontinued and appropriate therapy initiated.

The following adverse reactions have been observed in the clinical studies of GOHIBIC that supported the EUA. The adverse reaction rates observed in these clinical studies cannot be directly compared to rates in the clinical studies of other products and may not reflect the rates observed in clinical practice.

No drug interaction studies have been conducted with GOHIBIC.

Risk Summary There are no available data on GOHIBIC use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Placental transfer of monoclonal antibodies such as GOHIBIC is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy. In an enhanced pre- and post-natal (ePPND) study conducted in cynomolgus monkeys, placental transport of GOHIBIC was observed but there was no evidence of fetal harm following intravenous administration of GOHIBIC throughout pregnancy at doses 2.5 times the maximum recommended human dose (MRHD) of 800 mg on a mg/kg basis (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk for major birth defects and miscarriage in clinical recognized pregnancies is 2% - 4% and 15% - 20%, respectively. Data Animal Data In the ePPND study, pregnant cynomolgus monkeys received GOHIBIC from GD20 to GD22 (dependent on pregnancy determination), at the beginning of organogenesis, and once every 7 days until the end of gestation at intravenous doses up to 50.6 mg/kg/wk (2.5 times the MRHD on a mg/kg basis). There were no GOHIBIC-related adverse effects on maternal health, pregnancy outcome, embryo-fetal development, or neonatal growth and development up to 6 months of age (PND183). GOHIBIC crossed the placenta in cynomolgus monkeys and GOHIBIC plasma concentrations were similar in infants relative to maternal animals on PND28 and were 8-12 times higher in infants relative to maternal animals on PND91. GOHIBIC was not detected in infant plasma on PND183. Risk Summary There are no available data on the presence of GOHIBIC in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. Maternal IgG is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed infant to GOHIBIC are unknown. The lack of clinical data during lactation precludes clear determination of the risk of GOHIBIC to an infant during lactation. Therefore, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for GOHIBIC and any potential adverse effects on the breastfed child from GOHIBIC or from the underlying maternal condition. GOHIBIC is not authorized or approved for the emergency use in pediatric patients for the treatment of coronavirus disease 2019 (COVID-19) in hospitalized patients when initiated within 48 hours of receiving invasive mechanical ventilation (IMV), or extracorporeal membrane oxygenation (ECMO). Of the total number of GOHIBIC-treated patients in clinical studies for COVID-19 receiving invasive mechanical ventilation (IMV), or extracorporeal membrane oxygenation (ECMO), 53 (30%) were >65 years. No overall differences in effectiveness or safety of GOHIBIC have been observed between patients 65 years of age and older and younger adult patients.

How supplied GOHIBIC (vilobelimab) 200 mg/20 mL (10 mg/mL) injection is a clear to slightly opalescent, colorless solution in a single-dose vial (NDC 83000-110-04). Storage and Handling Store unopened vials refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Do not shake.

GOHIBIC is a chimeric monoclonal IgG4-kappa antibody that binds to C5a with a dissociation constant of 9.6pM and blocks its interaction with the C5a receptor. C5a is part of the complement system and is activated as part of the innate immune response initiating an inflammatory cascade that includes increased vascular permeability, coagulation, proinflammatory cytokine release, and recruitment and activation of neutrophils and other myeloid cells. The reduction of C5a plasma concentration was evaluated in PANAMO. The median plasma concentrations of C5a at baseline in patients with severe COVID-19 pneumonia requiring IMV or ECMO were elevated and the values were comparable between the GOHIBIC group (118.29 ng/mL) and the placebo group (104.62 ng/mL). In the GOHIBIC group, the median concentrations of C5a decreased to 14.53 ng/mL by Day 8 and remained at approximately this level up to Day 30 after the initiation of treatment. In the placebo group, the median concentrations of C5a remained approximately at the baseline level during the study up to Day 30 after the initiation of the treatment. However, the direct clinical relevance of C5a plasma concentration reduction is unclear. In healthy subjects, following a single intravenous infusion of GOHIBIC ranging from 2 mg/kg to 4 mg/kg, GOHIBIC C max showed dose proportionality while the AUC showed greater than dose proportionality. The elimination half-life of GOHIBIC following a 4 mg/kg single intravenous dose in healthy subjects was 95 hours. Pre-dose plasma samples were collected in patients with severe COVID-19 pneumonia requiring IMV or ECMO. Following intravenous infusion of GOHIBIC 800 mg on Days 1, 2, and 4, the pre-dose geometric mean (geometric CV%) plasma concentration of GOHIBIC on Day 8 was 137.9 µg/mL (51%). Drug Interaction Studies No drug interaction studies have been conducted with GOHIBIC.

Animal studies have not been conducted to evaluate the carcinogenic potential of GOHIBIC. The malignancy risk in humans from an antibody that binds C5a, such as GOHIBIC, is currently unknown. Male and female fertility parameters were evaluated as part of the 13-week and 26-week repeat-dose toxicity studies, respectively. There were no treatment-related changes to sperm morphology, count, or motility in male monkeys administered GOHIBIC for 13-weeks at intravenous doses up to 50.6 mg/kg/week (approximately 2.5 times the MRHD on a mg/kg basis). Following 26-weeks intravenous administration of GOHIBIC, there were no effects on female fertility including menstrual cyclicity identified at doses up to 50 mg/kg/week (approximately 2.5 time the MRHD on a mg/kg basis).

Clinical data supporting this EUA are based on PANAMO (NCT04333420), a Phase 3, double-blind, randomized, placebo-controlled multicenter trial evaluating GOHIBIC for the treatment of COVID-19 in adult (≥ 18 years) patients requiring IMV or ECMO. The multinational trial was conducted in Europe, Latin America, Russia, and South Africa. Efficacy analyses were based on 368 patients, 177 in the GOHIBIC group and 191 in the placebo group. The mean age of participation was 56 years [range: 22 to 81 years] and 68.5% were male. Common co-existing medical conditions included hypertension (46.2%), obesity (40.8%) and diabetes (29.6%) in the overall study population. All patients were mechanically ventilated and three patients in each arm were on ECMO. Additional demographics and baseline characteristics of patients in PANAMO are provided in Table 2. Table 2. Demographics and Baseline Characteristics of Patients in PANAMO GOHIBIC + SoC A total of 369 patients were randomized in the trial (178 to GOHIBIC and 191 to placebo), but one patient in the GOHIBIC group was randomized in error and not included in the efficacy analyses. (N=177) Placebo + SoC (N=191) Age Group, n (%)   18 – 39 years 22 (12.4%) 30 (15.7%)   40 – 65 years 102 (57.6%) 103 (53.9%)   > 65 years 53 (29.9%) 58 (30.4%) WHO 8-point ordinal scale score World Health Organization 8-point ordinal scale   6 – Intubation and mechanical ventilation 72 (40.7%) 59 (30.9%)   7 – Ventilation + additional organ support (vasopressors, renal replacement therapy, ECMO) 105 (59.3%) 132 (69.1%) Prior and concomitant medications   Dexamethasone or systemic corticosteroid 176 (99.4%) 188 (98.4%)   Baricitinib 6 (3.4%) 6 (3.1%)   Tocilizumab 30 (16.9%) 31 (16.2%)   Remdesivir 10 (5.6%) 11 (5.8%) The primary endpoint in the study was time to death through Day 28. The Kaplan-Meier estimated 28-Day mortality rate in the GOHIBIC group was 31.7% and the estimated rate in the placebo group was 41.6%, resulting in a hazard ratio of 0.67 (95% CI [0.48, 0.96], p<0.05, Table 3). Results were similar at Day 60 (Table 3). Mortality through day 28 and 60 in PANAMO are provided in Table 3. The percentage of patients alive and either discharged from the hospital or no longer requiring supplemental oxygen at Day 28 were comparable in the GOHIBIC (35.0%) and placebo (36.1%) groups. Table 3. Mortality through Day 28 and Day 60 in PANAMO GOHIBIC + SoC (N=177) Placebo + SoC (N= 191) Abbreviations: CI = confidence interval Day 28 Mortality   Number of Deaths 54 77   Percentage with Death Results from Kaplan-Meier estimates. Percentages will not be proportional to the number of deaths divided by the total number of patients due to missing values (8 patients missing mortality status in GOHIBIC + SoC and 9 in placebo + SOC). 31.7% 41.6%   Hazard Ratio Results from Cox proportional hazards regression with treatment and age as covariates. P-values < 0.05. (95% CI) 0.67 (0.48, 0.96)   Risk Difference Results based on a logistic regression model with treatment and age as covariates, and missing values handled by multiple imputation. (95% CI) -11.2% (-21.0%, -1.4%)   Day 60 Mortality   Number of Deaths 62 87   Percentage with Death 36.5% 47.2%   Hazard Ratio (95% CI) 0.67 (0.48, 0.93)   Risk Difference (95% CI) -12.2% (-22.0%, -2.4%)

Emergency Use Authorization (EUA) of GOHIBIC for Coronavirus Disease 2019 (COVID-19) You are being given this Fact Sheet because your healthcare provider believes it is necessary to provide you with GOHIBIC (vilobelimab) for the treatment of coronavirus disease 2019 (COVID-19). Taking GOHIBIC may benefit adults in the hospital with COVID-19 who require a machine that helps with breathing (invasive mechanical ventilation) or a machine that adds oxygen to the blood outside the body (extracorporeal membrane oxygenation or ECMO). This Fact Sheet contains information to help you understand the potential risks and potential benefits of receiving GOHIBIC. The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) to make GOHIBIC available for use as a treatment for certain adults with COVID-19 (for more details about EUA please see " What is an Emergency Use Authorization? " at the end of this document). GOHIBIC is not FDA-approved for this use. Read this Fact Sheet for information about GOHIBIC. Talk to your healthcare provider about your options or if you have any questions. It is your choice for you to take GOHIBIC or stop it at any time. What is COVID-19? COVID-19 is caused by a virus called a coronavirus. You can get COVID-19 through contact with another person who has the virus. COVID-19 illnesses have ranged from very mild (including some with no reported symptoms) to severe, including illness resulting in death. While information so far suggests that most COVID-19 illness is mild, serious illness can happen and may cause some of your other medical conditions to become worse. People of all ages with severe, long-lasting (chronic) medical conditions like heart disease, lung disease, and diabetes, for example, seem to be at higher risk of being hospitalized for COVID-19. What are the symptoms of COVID-19? The symptoms of COVID-19 may include fever, cough, and shortness of breath, which can appear 2 to 14 days after exposure. Serious illness, including breathing problems, can occur and may cause your other medical conditions to become worse. What is GOHIBIC? GOHIBIC is an investigational medicine used for the treatment of COVID-19 in hospitalized adults when initiated within 48 hours of receiving invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO). GOHIBIC is investigational because it is still being studied. GOHIBIC is not FDA-approved to treat COVID-19. There is limited information known about the safety or effectiveness of using GOHIBIC to treat people in the hospital with COVID-19. Available results from clinical trials in adults indicate that treatment with GOHIBIC may decrease the risk of dying in hospitalized adults with COVID-19 when initiated within 48 hours of receiving invasive mechanical ventilation or ECMO. The safety and effectiveness of GOHIBIC have not been studied in children hospitalized with COVID-19. The FDA has authorized the emergency use of GOHIBIC for the treatment of COVID-19 in hospitalized adults when initiated within 48 hours of receiving invasive mechanical ventilation or ECMO under an EUA. For more information on EUA, see the " What is an Emergency Use Authorization (EUA)? " section at the end of this Fact Sheet. What should I tell my healthcare provider before I receive GOHIBIC? Tell your healthcare provider about all of your medical conditions including if you: Have allergies. Have an infection other than COVID-19. Are pregnant or plan to become pregnant. Are breast-feeding or plan to breastfeed. Have any serious illnesses. Tell your healthcare provider about all the medicines you take, including prescription and, over-the-counter medicines, vitamins, and herbal supplements. How will I receive GOHIBIC? GOHIBIC is given to you through a vein (intravenous or IV) as an infusion. GOHIBIC will be given up to six doses. The first dose will be given within 48 hours of a tube being inserted (intubation) and a machine to help you breathe (ventilator), this is Day 1. The following administration of GOHIBIC will be given on Days 2, 4, 8, 15, and 22 as long as you are hospitalized [even discharged from the Intensive Care Unit (ICU)]. What are the important possible side effects of GOHIBIC? GOHIBIC may cause serious side effects, including: Serious infections: GOHIBIC is a medicine that affects your immune system. GOHIBIC can lower the ability of your immune system to fight infections other than COVID-19. Allergic Reactions: Serious allergic reactions can happen during or after treatment with GOHIBIC . These reactions may be severe or life-threatening. Signs and symptoms of a serious allergic reaction with GOHIBIC may include: trouble breathing rash swelling of your face, eyes, lips mouth, tongue and throat. The most common side effects of GOHIBIC may include: Lung infection, sepsis, sudden confusion, sudden lung artery blockage, high blood pressure, collapsed lung, venous blood clotting (usually in the leg), herpes infection, certain infections caused by enterococci, urinary tract infection, low blood oxygenation, low platelets, the presence of air in the space in the chest between the two lungs, infection of the respiratory tract, heart arrythmia, constipation, and rash. What other treatment choices are there? Olumiant (baricitinib), Actemra (tocilizumab), and Veklury (remdesivir) are FDA-approved medicines for the treatment of COVID-19 in hospitalized patients who require invasive mechanical ventilation or ECMO. Talk with your healthcare provider to see if those therapies are appropriate for you. Like GOHIBIC, FDA may allow for the emergency use of other medicines to treat people in the hospital with COVID-19. Go to https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization for information on emergency use of other medicines that are not approved by FDA to treat people in the hospital with COVID-19. Please consult with your healthcare provider on which medicine or combination of medicines might be right for you. Your healthcare provider may talk with you about clinical trials you may be eligible for. It is your choice to be treated or not to be treated with GOHIBIC. Should you decide not to receive it, it will not change your standard medical care. What if I am pregnant or breastfeeding? There is no experience giving GOHIBIC to pregnant women or breastfeeding mothers. GOHIBIC may harm your unborn baby. It is unknown if GOHIBIC passes into your breast milk. If you are pregnant or breastfeeding, discuss your options and specific situation with your healthcare provider. How do I report side effects or adverse events with GOHIBIC? Contact your healthcare provider if you have any side effects that bother you or do not go away. Report side effects to FDA MedWatch at www.fda.gov/medwatch or call 1-800-FDA-1088. You may also report side effects to InflaRx GmbH by calling 1-888-254-0602. How can I learn more about COVID-19? Ask your healthcare provider Visit https://www.cdc.gov/COVID19 Contact your local or state public health department What is an Emergency Use Authorization (EUA)? The United States FDA has made GOHIBIC available under an emergency access mechanism called an EUA. The EUA is supported by a Secretary of Health and Human Service (HHS) declaration that circumstances exist to justify the emergency use of drugs and biological products during the COVID-19 pandemic. GOHIBIC, as a treatment for COVID-19 has not undergone the same type of review as an FDA-approved product for this indication. The FDA may issue an EUA when certain criteria are met, which includes that there are no adequate, approved, and available alternatives. In addition, the FDA decision is based on the totality of scientific evidence available showing that it is reasonable to believe that the product meets certain criteria for safety, performance, and labeling and may be effective in treatment of patients during the COVID-19 pandemic. All of these criteria must be met to allow for the product to be used in the treatment of patients during the COVID-19 pandemic. The EUA for GOHIBIC as a treatment for certain people with COVID-19 is in effect for the duration of the COVID-19 declaration justifying emergency use of this product, unless terminated or revoked (after which the products may no longer be used under the EUA). This Fact Sheet may be updated as new data become available. The most recent version of this Fact Sheet is available at www.gohibic.com . Manufactured by: InflaRx GmbH Winzerlaer Street 2 07745 Jena Germany © 2023, InflaRx. All rights reserved. Authorized: 04/2023

NDC 83000-110-04 Rx-only GOHIBIC (vilobelimab) injection 200 mg/20 mL (10 mg/mL) For intravenous infusion after dilution For use under Emergency Use Authorization 4 x 20 mL single-dose vials-Discard unused portion PRINCIPAL DISPLAY PANEL - 200 mg/20 mL Vial Carton