Pemivibart (Monograph)

Drug class: Monoclonal Antibodies

Introduction

Pemivibart, a recombinant human IgG₁ monoclonal antibody that targets the SARS-CoV-2 spike protein receptor binding domain, is an antiviral agent.

Uses for Pemivibart

Pemivibart has the following uses:

Pemivibart is available under an emergency use authorization (EUA) for the pre-exposure prophylaxis of coronavirus disease 2019 (COVID-19) in adults and adolescents (12 years of age and older weighing at least 40 kg) who are not currently infected with SARS-CoV-2 and who have not had a known recent exposure to an individual infected with SARS-CoV-2 and who have moderate-to-severe immune compromise due to a medical condition or receipt of immunosuppressive medications or treatments and are unlikely to mount an adequate immune response to COVID-19 vaccination.

Medical conditions or treatments that may result in moderate to severe immune compromise and an inadequate immune response to COVID-19 vaccination include:

• Active treatment for solid tumor and hematologic malignancies.

• Hematologic malignancies associated with poor responses to COVID-19 vaccines regardless of current treatment status (e.g., chronic lymphocytic leukemia, non-Hodgkin lymphoma, multiple myeloma, acute leukemia).

• Receipt of solid-organ transplant or an islet transplant and taking immunosuppressive therapy.

• Receipt of chimeric antigen receptor (CAR)-T-cell or hematopoietic stem cell transplant (within 2 years of transplantation or taking immunosuppressive therapy).

• Moderate or severe primary immunodeficiency (e.g., common variable immunodeficiency disease, severe combined immunodeficiency, DiGeorge syndrome, Wiskott-Aldrich syndrome).

• Advanced or untreated HIV infection (people with HIV and CD4 cell counts <200/mm³ , history of an AIDS-defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV).

• Active treatment with high-dose corticosteroids (i.e., ≥20 mg prednisone or equivalent per day when administered for ≥2 weeks), alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, and biologic agents that are immunosuppressive or immunomodulatory (e.g., B-cell depleting agents).

On March 22, 2024, FDA issued an EUA that permits the use of pemivibart for pre-exposure prophylaxis of COVID-19 in certain adults and adolescents. FDA issued the EUA after concluding that emergency use of the drug for the prevention of COVID-19 met the requisite EUA criteria. The EUA for pemivibart will end when circumstances justifying the EUA no longer exist or when there is a change in approval status of the drug such that the EUA is no longer needed. To mitigate the risks of the drug, the EUA requires that healthcare providers prescribing pemivibart comply with certain mandatory requirements, including providing the patient with information consistent with the EUA Fact Sheet and ensuring that all medication errors and all serious adverse events related to use of the drug are reported to the FDA. For additional information, consult the EUA letter of authorization, EUA fact sheet for healthcare providers, and EUA fact sheet for patients and caregivers.

Limitations of Authorized Use

• Pemivibart is not authorized for the treatment of COVID-19 or for post-exposure prophylaxis of COVID-19 in individuals who have been exposed to someone infected with SARS-CoV-2.

• Pre-exposure prophylaxis with pemivibart is not a substitute for vaccination in individuals for whom COVID-19 vaccination is recommended. Individuals for whom COVID-19 vaccination is recommended, including individuals with moderate-to-severe immune compromise who may derive benefit from COVID-19 vaccination, should receive COVID-19 vaccination.

• In individuals who have recently received a COVID-19 vaccine, pemivibart should be administered at least 2 weeks after vaccination.

Pemivibart Dosage and Administration

General

Pemivibart is available in the following dosage form(s) and strength(s):

Injection: 500 mg/4 mL (125 mg/mL) in a single-dose vial.

Administration

IV Administration

• Administer by IV infusion over a minimum of 60 minutes.

• Administer only in settings in which healthcare providers have immediate access to medications to treat a severe hypersensitivity reaction, such as anaphylaxis, and the ability to activate the emergency medical system (EMS), as necessary.

• Dilute commercially available injection concentrate prior to IV infusion.

• Remove pemivibart vials from refrigerated storage and allow to equilibrate to room temperature (18℃ to 26℃) for 10 minutes before preparation. Do not expose to direct heat. Do not shake vials.

• Prepare IV bag by removing and discarding 36 mL from a 50 mL prefilled bag of 0.9% sodium chloride for IV injection.

• Withdraw 36 mL of pemivibart from 9 vials into appropriately sized polypropylene syringe(s) (e.g., one 40 mL syringe or two 20 mL syringes) and inject into prepared 0.9% sodium chloride IV bag.

• The final product for administration will contain 50 mL: 36 mL of pemivibart and 14 mL of 0.9% sodium chloride.

• Administer immediately; if immediate administration is not possible, the diluted solution may be stored at room temperature under ambient light for up to 4 hours. Do not shake the diluted solution.

• Attach infusion set including inline 0.2-micron filter to prepared IV bag, then prime the infusion set.

• Administer the entire 50 mL infusion using infusion pump or gravity infusion set over a minimum of 60 minutes. Due to potential overfill, the entire contents of prepared IV bag should be administered to avoid underdosing.

• Once infusion is complete, flush line with 0.9% sodium chloride.

• Clinically monitor patients during infusion and observe patients for at least 2 hours after infusion is complete.

• See Full Fact Sheet for Healthcare Providers for details on preparation and administration.

Dosage

Pediatric Patients

Prophylaxis of COVID-19

The initial dosage of pemivibart in adolescents (12 years of age and older weighing at least 40 kg) is 4500 mg administered as a single IV infusion. If ongoing protection is necessary, repeat doses of 4500 mg may be administered as a single IV infusion every 3 months. Repeat dosing should be timed from the date of the most recent pemivibart dose.

Adults

Prophylaxis of COVID-19

The initial dosage of pemivibart in adults is 4500 mg administered as a single IV infusion. If ongoing protection is necessary, repeat doses of 4500 mg may be administered as a single IV infusion every 3 months. Repeat dosing should be timed from the date of the most recent pemivibart dose.

Cautions for Pemivibart

Contraindications

Pemivibart is contraindicated in individuals with previous severe hypersensitivity reactions, including anaphylaxis, to any component of pemivibart.

Warnings/Precautions

Warnings

Anaphylaxis

Anaphylaxis has been observed with pemivibart in 4 of 623 (0.6%) participants in a clinical trial. Two participants had anaphylaxis during the first infusion, and two participants had anaphylaxis during the second infusion. Anaphylaxis can be life-threatening, and two of the anaphylactic reactions in the clinical trial were reported as life-threatening. Manifestations included pruritus, flushing, urticaria, erythema, angioedema, diaphoresis, dizziness, tinnitus, wheezing, dyspnea, chest discomfort, and tachycardia. In all 4 cases, pemivibart was permanently discontinued. Prior to administering Pemivibart, consider the potential benefit of COVID-19 prevention along with the risk of anaphylaxis. Administer pemivibart only in settings in which healthcare providers have immediate access to medications to treat anaphylaxis and the ability to activate the emergency medical system (EMS), as necessary.

Clinically monitor individuals during the 60-minute infusion and for at least 2 hours after completion of the infusion. If signs or symptoms of an anaphylactic reaction occur, immediately discontinue administration, and initiate appropriate medications and/or supportive therapy. Discontinue pemivibart use permanently in individuals who experience signs or symptoms of anaphylaxis.

Hypersensitivity and Infusion-Related Reactions

Hypersensitivity and infusion-related reactions occurring during the infusion and up to 24 hours after the infusion have been observed with administration of pemivibart. Hypersensitivity or infusion-related reactions may be severe or life threatening. If signs or symptoms of a clinically significant hypersensitivity or infusion-related reaction occur, immediately discontinue administration, and initiate appropriate medications and/or supportive therapy. Signs and symptoms of hypersensitivity or infusion-related reactions may include fever, difficulty breathing, reduced oxygen saturation, chills, fatigue, arrhythmia (e.g., atrial fibrillation, sinus tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, nausea, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, vasovagal reactions (e.g., presyncope, syncope), dizziness, and diaphoresis.

If a mild infusion-related reaction occurs, consider slowing or stopping the infusion and administer appropriate medications and/or supportive care. Clinically monitor individuals during infusion and for at least 2 hours after completion of the infusion for signs and symptoms of hypersensitivity. Hypersensitivity reactions occurring more than 24 hours after the infusion have also been reported with the use of SARS-CoV-2 monoclonal antibodies under Emergency Use Authorization.

Risk of Cross-Hypersensitivity With COVID-19 Vaccines

Pemivibart contains polysorbate 80, which is in some COVID-19 vaccines and is structurally similar to polyethylene glycol (PEG), an ingredient in other COVID-19 vaccines. For individuals with a history of a severe hypersensitivity reaction to a COVID-19 vaccine, consider consultation with an allergist-immunologist prior to pemivibart administration.

Administration of pemivibart should be done under the supervision of a healthcare provider with appropriate medical support to manage severe hypersensitivity reactions. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur during administration of pemivibart, immediately discontinue administration and initiate appropriate medications and/or supportive care. Clinically monitor individuals after infusion and observe for at least 2 hours.

Risk for COVID-19 Due to SARS-CoV-2 Viral Variants Not Neutralized by Pemivibart

Certain SARS-CoV-2 viral variants may emerge that are not neutralized by monoclonal antibodies such as pemivibart. Pemivibart may not be effective at preventing COVID-19 caused by these SARS-CoV-2 viral variants.

Inform individuals of the increased risk, compared to other variants, for COVID-19 due to emergent SARS-CoV-2 viral variants not neutralized by pemivibart. If signs or symptoms of COVID-19 occur, advise individuals to test for COVID-19 and seek medical attention, including starting treatment for COVID-19 as appropriate. Symptoms of COVID-19 may include fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, or diarrhea.

Specific Populations

Pregnancy

There are insufficient data to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Pemivibart should only be used during pregnancy if the potential benefit outweighs the potential risk for the mother and the fetus.

Nonclinical reproductive toxicity studies have not been performed with pemivibart. In tissue cross-reactivity studies using human fetal tissues, no off-target binding was detected for pemivibart. Human immunoglobulin G1 (IgG1) antibodies are known to cross the placental barrier; therefore, pemivibart has the potential to be transferred from the mother to the developing fetus. It is unknown whether the potential transfer of pemivibart provides any treatment benefit or risk to the developing fetus.

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 US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Lactation

There are no available data on the presence of pemivibart in 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 developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for pemivibart and any potential adverse effects on the breastfed infant from pemivibart.

Pediatric Use

Pemivibart is not authorized for use in pediatric patients less than 12 years of age or weighing less than 40 kg. The safety and effectiveness of pemivibart have not been established in pediatric patients.

The recommended dosing regimen is expected to result in comparable serum exposures of pemivibart in adolescents 12 years of age and older and weighing at least 40 kg as observed in adults, since adults with similar body weight have been included in the CANOPY study.

Geriatric Use

Of the 623 participants who received pemivibart in the CANOPY trial, 156 (25%) were ≥65 years of age and 31 (5%) were ≥75 years of age. Based on population pharmacokinetic (PK) analyses, there was no clinically meaningful difference of age on the PK of pemivibart.

Hepatic Impairment

The effect of hepatic impairment on the PK of pemivibart is unknown.

Renal Impairment

Pemivibart is not eliminated intact in the urine, thus renal impairment is not expected to affect the exposure of the drug. Similarly, dialysis is not expected to impact the PK of pemivibart.

Common Adverse Effects

The most common adverse events (all grades, incidence ≥2%) observed in participants who have moderate-to-severe immune compromise treated with pemivibart included systemic and local infusion-related or hypersensitivity reactions, upper respiratory tract infection, viral infection, influenza-like illness, fatigue, headache, and nausea.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments.

Drug-drug interaction studies have not been performed. Pemivibart is not renally excreted or metabolized by cytochrome P-450 (CYP) enzymes; therefore, interactions with concomitant medications that are renally excreted or that are substrates, inducers, or inhibitors of CYP enzymes are unlikely.

Actions

Mechanism of Action

Pemivibart is a recombinant human monoclonal IgG1λ antibody that targets the SARS-CoV-2 spike protein receptor binding domain (RBD), thereby inhibiting virus attachment to the human ACE2 receptor on host cells. Amino acid substitutions in the Fc region (M435L/N441A) of pemivibart extend serum half-life. Pemivibart binds the spike RBD proteins of ancestral SARS-CoV-2 B.1 (D614G) and Omicron variants BA.1, BA.2, and BA.4/5 with equilibrium dissociation constants (KD) of 2.1 nM, 18 nM, 13.5 nM, and 15.9 nM, respectively, and blocks attachment of ancestral SARS-CoV-2 and BA.2.86 variant RBD proteins to the human ACE2 receptor with IC50 values of 0.068 nM (10 ng/mL) and 23 nM (3370 ng/mL), respectively.

Pemivibart neutralized authentic SARS-CoV-2 isolates in Vero E6 or Vero E6-TMPRSS2 cells with EC50 values of 0.165-0.230 nM (24.3-34 ng/mL) against B.1, and 0.075 nM (11 ng/mL) against B.1.617.2 (Delta). For Omicron variants, EC50 values were 0.096 nM (14.2 ng/mL) against BA.1, 0.039 nM (5.8 ng/mL) against BA.2, 0.175 nM (25.8 ng/mL) against BA.4.1, 0.80- 4.48 nM (118-661.2 ng/mL) against XBB.1.16, 1.97-3.25 nM (290-479.9 ng/mL) against XBB.1.5, 9.8 nM (1,445 ng/mL) against EG.5.1, 3.59 nM (529.4 ng/mL) against HV.1, and 0.43 nM (63.6 ng/mL) against JN.1.

There is a potential risk of prophylaxis failure due to the emergence of a pemivibart-resistant SARS-CoV-2 variant. Prescribing healthcare providers should consider the prevalence of SARS-CoV-2 variant.

Advice to Patients

• The Fact Sheet for Patients, Parents or Caregivers must be provided to the patient, parent, and caregiver prior to administration of pemivibart.

• Inform individuals that anaphylaxis has been observed with pemivibart. Advise individuals that they will be monitored during and for at least 2 hours after completion of the infusion. In those who experience signs or symptoms of anaphylaxis, pemivibart use will be discontinued permanently.

• Inform individuals that hypersensitivity and infusion-related reactions have occurred during the infusion and up to 24 hours after the infusion with pemivibart. These hypersensitivity or infusion-related reactions may be severe or life threatening. Inform individuals that they will be monitored during and for at least 2 hours after completion of the infusion for signs and symptoms of hypersensitivity.

• Inform individuals that they may need to receive additional doses of pemivibart every 3 months if ongoing protection is needed.

• Certain SARS-CoV-2 viral variants may emerge that are not neutralized by monoclonal antibodies such as pemivibart. Pemivibart may not be effective at preventing COVID-19 caused by these SARS-CoV-2 viral variants. Inform individuals of the increased risk, compared to other variants, for COVID-19 due to SARS-CoV-2 viral variants not neutralized by pemivibart. If signs or symptoms of COVID-19 occur, advise individuals to test for COVID-19 and seek medical attention, including starting treatment for COVID-19 as appropriate.

Additional Information

AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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