Pemivibart - Uses, Dosage, Precautions, Side Effects, and Pharmacological Aspects

Overview

The Pemivibart injection is an intravenous (through the vein) emergency treatment approved by the US FDA (United States Food and Drug Administration) for emergency use starting in March 2024. The intravenous treatment is to be administered for pre-exposure prophylaxis of COVID-19 (Coronavirus 2019). It is intravenous, neutralizing the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus. It is, therefore, suited for people at risk of developing severe COVID-19, especially those with moderate to severe immune compromise. Pemivibart is under active clinical studies to assess its effectiveness and safety. Data have provided substantial evidence for its use under emergency use authorization.

Drug Group

Pemivibart is classified as a biological drug and part of a broader group of protein-based therapies commonly used in biotech treatments. It is a monoclonal antibody (mAb) approved under emergency use authorization (EUA) for pre-exposure prophylaxis (PrEP) against COVID-19 in high-risk populations.

Indications

The US FDA (United States Food and Drug Administration) has approved an emergency use authorization (EUA) for Pemivibart, an unapproved SARS-CoV-2 spike protein-directed attachment inhibitor, for COVID-19 pre-exposure prophylaxis in adults and adolescents (12 years and older, weighing at least 88 pounds) who meet the following criteria:

• Individuals are not currently infected with SARS-CoV-2 and have not had recently known exposure to someone infected with the virus.

• Persons with moderate-to-severe immunological impairment because of a medical disease or immunosuppressive treatments are unlikely to mount a sufficient immunological response to the COVID-19 vaccine.

While Pemivibart is authorized for emergency use as described, it is not FDA-approved for any indication, including pre-exposure prophylaxis of COVID-19.

Limitations on Pemivibart Use:

• Pemivibart is not authorized to treat post-exposure prophylaxis of COVID-19 (authorized for emergency use only).

• Its use is restricted to when the national variant frequency with reduced susceptibility to Pemivibart is less than or equal to 90 percent.

• Pemivibart is not a replacement for vaccination. Individuals eligible for COVID-19 vaccination should receive it, even if they have moderate-to-severe immune compromise.

• Pemivibart should be administered at least two weeks after receiving a COVID-19 vaccine.

Emergency Use Justification: The COVID-19 pandemic, caused by SARS-CoV-2, prompted the U.S. (United States) Department of Health and Human Services (HHS) to declare a public health emergency, allowing emergency use authorizations (EUAs) for unapproved products. EUAs are granted when:

• The agent can cause a serious or life-threatening illness.

• Scientific evidence suggests the product may be effective, and its potential benefits outweigh the risks.

• There is no adequate, approved, and available alternative for diagnosing, preventing, or treating the condition.

Dosage Forms and Available Strengths

Pemivibart is available as an injection containing 500 mg (milligrams) per 4 mL (milliliters) (125 mg/mL or milligrams per milliliter) in a single-dose vial.

For Patients

How Does Pemivibart Work As Pre-Exposure Prophylaxis for COVID-19?

Pemivibrant is a type of antibody targeting the SARS-CoV-2 virus, which causes the disease COVID-19. Its work involves explicitly interacting with the spike protein receptor binding domain (RBD) on the virus; this makes it impossible for the virus to attach to human cells, which is necessary for infection. Its structure was slightly modified to make it stay longer in the body. It has effectively bind different types of variants, including early strains and some of the Omicron variants. So, it is versatile and can cover numerous mutations. It can already prevent the virus from attaching to human cells at deficient concentrations, making this a potent tool against COVID-19 infections.

How Is Pemivibart Administered?

Pemivibrant must be prepared and administered by a qualified healthcare provider using an aseptic technique. Pemivibrant is administered through an intravenous (IV) infusion.

Here is a step-by-step overview of the administration process:

• Ensure the administration takes place in a healthcare setting equipped to manage severe allergic reactions like anaphylaxis.

• Attach an IV extension set with a 0.2-micron filter to the prepared saline bag containing Pemivibrant. Prime the infusion set to remove any air bubbles.

• Administer the entire 50 mL solution using an infusion pump or a gravity infusion set. The infusion should take at least 60 minutes to complete.

• After the infusion, flush the IV line with 0.9 percent sodium chloride to ensure all medication is delivered.

• Monitor the patient during the infusion and for at least two hours afterward for any adverse reactions.

What Are the Side Effects of Pemivibart?

The side effects are as follows:

• Anaphylaxis: Symptoms included dyspnea (shortness of breath), flushing, and urticaria (red, itchy, raised welts or bumps).

• Systemic Infusion-Related Reactions and Hypersensitivity Reactions: Common symptoms included fatigue, headache, tachycardia (rapid heartbeat), and myalgia (muscle pain).

• Local Infusion Site Reactions: Reactions included bruising and erythema (redness).

Other Common Adverse Events:

• Upper respiratory tract infection.

• Viral infection.

• Influenza-like illness.

• Fatigue.

• Headache.

• Nausea.

Serious Adverse Events Include:

• Death.

• Life-threatening events (example: Heart attack).

• Hospitalization or extended hospitalization.

• Significant impairment or disturbance to typical living functions.

• Congenital anomalies or birth defects.

• Other important medical events require intervention to prevent serious outcomes.

What Are the Things to Inform the Doctor Before Taking Pemivibart?

Before starting with Pemivibart, discuss any allergies, in particular cross-sensitivities with other medications that work through the exact mechanism and a history of allergic reactions to some drugs linked to severe allergic reactions. Remember to provide the doctor with an extensive list of medications individuals take, including over-the-counter and supplement medicines that might interact or cause a type of interaction. Also, note if a patient has renal (kidney) issues or has been afflicted with immune-compromising conditions. Finally, if a patient is pregnant or planning to conceive or breastfeed, it is compulsory to inform the physician.

Dietary Considerations

None.

Missed Dose

Contact the doctor if the dose is missed.

Overdose

Doses exceeding 4500 mg of Pemivibart (the authorized dose) were not tested in clinical studies. There is no specific treatment for an overdose of Pemivibart.

Storage and Handling

Pemivibart injection is a sterile, preservative-free solution that appears clear to slightly opalescent and ranges from colorless to yellow. It is provided in a single-dose 6R vial for intravenous infusion only. Each vial contains 500 mg of Pemivibart in 4 mL (125 mg/mL), with nine vials packaged per carton (NDC 81960-031-03). Store unopened vials in their original carton in a refrigerator at two to eight degrees Celsius (36 to 46 degrees Fahrenheit) to protect them from light. Do not freeze or shake or use if the seal is broken or missing.

Disposal:

Unused or expired Pemivibart should be disposed of following FDA guidelines. If no take-back programs are available, Combine the drug with a substance such as dirt or cat litter in a sealed container and dispose of it in the household trash. Only flush those medications down the toilet if specifically instructed to do so. In all cases, check with the healthcare provider or pharmacist for disposal instructions.

For Doctors

Description:

Pemivibart is a 147.51-kDa human IgG1, or immunoglobulin G1 monoclonal antibody developed utilizing a Chinese hamster ovary cell line. Pemivibart injection is a sterile, preservative-free solution that is clear or slightly opalescent and colorless to yellow. It is intended for intravenous infusion after dilution.

Each 4 mL of the solution contains 500 mg of Pemivibart, along with the following ingredients: glycine (33.03 mg), L-arginine hydrochloride (63.2 mg), L-histidine (3.67 mg), L-histidine hydrochloride monohydrate (3.43 mg), L-methionine (5.97 mg), polysorbate 80 (1.2 mg), and sterile water for injection (USP). The solution's pH (potential of hydrogen) is 6.2.

Dose:

• Initial Dosing: For adults and adolescents (aged 12 and older, weighing at least 88 pounds), the initial dose of Pemivibart is 4500 mg, given as a single intravenous infusion.

• Repeat Dose: The repeat dosage is also 4500 mg, administered as a single IV infusion every three months from the date of the most recent Pemivibart dose.

Warnings and Precautions

• Anaphylaxis: In clinical trials, four out of 623 participants (0.6 percent) experienced anaphylaxis following Pemivibrant administration. Two cases occurred during the first infusion and two during the second. Anaphylaxis, a life-threatening condition, presents with symptoms such as itching, flushing, hives, swelling, wheezing, difficulty breathing, and rapid heart rate. In two cases, the reactions were classified as life-threatening. All four participants were withdrawn from the study, and Pemivibrant was permanently discontinued for them.

Before administering Pemivibrant, healthcare providers must weigh the benefits of preventing COVID-19 against the risk of anaphylaxis. Administration should only occur in a medical setting where emergency treatments for anaphylaxis are immediately accessible. Patients should be closely monitored throughout the 60-minute infusion and for at least two hours afterward. If any signs of anaphylaxis arise, the infusion should be discontinued promptly, and proper medical care should begin.

• Hypersensitivity and Infusion-Related Reactions: Pemivibrant can induce serious hypersensitivity or infusion-related responses during the infusion or within 24 hours afterward. Symptoms may include fever, chills, breathing difficulty, arrhythmias, hypotension, hypertension, chest pain, or edema. The reactions can be life-threatening and require immediate discontinuation of the infusion and initiation of supportive care. If a mild reaction occurs, the infusion can be slowed or stopped, and patients should be monitored for at least two hours post-infusion. Additionally, delayed hypersensitivity reactions have been reported beyond 24 hours after infusion with SARS-CoV-2 monoclonal antibodies, including Pemivibrant.

• Cross-Hypersensitivity Risk with COVID-19 Vaccines: Pemivibrant contains polysorbate 80, an ingredient also found in some COVID-19 vaccines and structurally related to polyethylene glycol (PEG), present in others. Individuals with a history of severe hypersensitivity to COVID-19 vaccines should consult an allergist-immunologist before receiving Pemivibrant. Pemivibrant should be administered under medical supervision, with appropriate emergency support readily available to manage severe hypersensitivity or anaphylaxis. Patients should be monitored during and after infusion for at least two hours.

• Efficacy Concerns with SARS-CoV-2 Variants: Certain SARS-CoV-2 variants may significantly reduce the efficacy of Pemivibrant. Viral variants with reduced susceptibility could render Pemivibrant less effective for COVID-19 prevention. Patients should be informed about the increased risk posed by these emergent variants, which are more virulent. They should be educated to come in at the earliest possible time with symptoms of COVID-19 so that a test for COVID-19 may be conducted and seek medical attention within the shortest time possible once treated for COVID-19.

What Are the Pharmacological Actions of Pemivibart?

Mechanism of Action: Pemivibart is a human monoclonal antibody designed to fight the SARS-CoV-2 virus. It specifically targets a part of the virus called the receptor binding domain (RBD) on the spike protein. By binding to the RBD, Pemivibart prevents the virus from attaching to the human ACE2 receptor on cells, which stops the infection.

To stay active in the body longer, Pemivibart has modifications in its structure that extend its half-life. It effectively binds to different variants of SARS-CoV-2, including the original strain and several Omicron variants, with very strong binding affinities. This ability allows it to block the virus from attaching to human cells, helping to prevent COVID-19 infection.

Pharmacodynamics: Data suggest a positive link between serum-neutralizing antibody levels and the effectiveness of COVID-19 pre-exposure prophylaxis, based on studies before the Omicron variant. After a single IV dose of 4500 mg of Pemivibart, geometric mean titers ranged from 2942 on day 90 to 19227 at the end of the infusion on day one. Following a repeat dose every three months, steady-state titers are expected to be about 33 percent higher than those after the first dose.

Pharmacokinetics:

• After a single intravenous dose of 4500 mg in adults, the pharmacokinetic parameters for Pemivibart are as follows: the maximum concentration (Cmax) is 1750 μg/mL or micrograms per milliliter, with concentrations of 460 μg/mL on Day 28 and 175 μg/mL on Day 90. The three-month area under the curve (AUC) is 36,600 days × μg/mL, and the half-life (T1/2) is 44.8 days. The accumulation ratio is 1.33, the clearance (CL) is 0.0909 L/d or liters per day, and the volume of distribution (Vss) is 5.54 L (liters).

• In terms of metabolism, Pemivibart is broken down through the same pathways as natural IgG antibodies. It is unlikely to be excreted through the kidneys.

• When considering specific populations, age, sex, and race do not significantly affect the pharmacokinetics of Pemivibart. Body weight within the range of 95 to 419 pounds is also not expected to have a notable impact. The immune-compromised status of patients does not influence the drug's pharmacokinetics.

• The pharmacokinetics of Pemivibart have not been evaluated in pediatric patients, but it is anticipated that those aged 12 and older who weigh at least 88 pounds will have similar exposure levels to adults. Renal impairment is not anticipated to influence the pharmacokinetics, and hepatic impairment is also unlikely to influence the drug's behavior in the body, as Pemivibart is degraded in a manner similar to other IgG (immunoglobulin G) antibodies.

Non-Clinical Toxicity:

Studies on carcinogenicity, mutagenicity, and reproductive toxicity have not been performed with Pemivibart. In a toxicology study involving rats, Pemivibart showed no adverse effects when administered intravenously. Additionally, tissue cross-reactivity studies using human adult and fetal tissues found no off-target binding with Pemivibart.

What Are the Contraindications of Pemivibart?

Pemivibrant should not be used in individuals who have a history of severe hypersensitivity reactions, including anaphylaxis, to any of its components.

What Are the Drug Interactions of Pemivibart?

Drug-drug interaction studies have not been conducted. Pemivibart is neither renally (through kidneys) excreted nor metabolized by cytochrome P450 enzymes, making interactions with other medications that are renally excreted or that act as substrates, inducers, or inhibitors of these enzymes unlikely.

Clinical Studies

The EUA for Pemivibart is supported by an immunobridging approach that evaluates its effectiveness for COVID-19 pre-exposure prophylaxis using serum neutralization data from other mAbs, including Adintrevimab. The ongoing CANOPY trial involves 623 adults, divided into Cohort A (those with moderate-to-severe immune compromise) and Cohort B (those without such compromise). Results indicate that Pemivibart significantly reduced COVID-19 cases in Cohort B, with only one case (0.3 percent) reported through Month three compared to eight cases (five percent) in the placebo group. Although Cohort A showed no COVID-19-related hospitalizations, two all-cause deaths were recorded.

Use in Specific Populations

• Pregnancy: There is not enough data to determine the risk of major birth defects, miscarriage, or negative outcomes from using Pemivibart during pregnancy. It should only be used if the benefits outweigh the risks for both mother and fetus. Although studies have not been done specifically on Pemivibart, it may transfer to the fetus since it is an IgG1 antibody. The background risk for birth defects and miscarriage in the general population is estimated at two to four percent and 15 to 20 percent, respectively.

• Lactation: There is no evidence of Pemivibart in human or animal milk and its effects on breastfed infants. While maternal IgG is present in breast milk, the benefits of breastfeeding should be weighed against any potential risks from Pemivibart.

• Pediatric Use: Pemivibart is not authorized for children under 12 years old or those weighing less than 88 pounds. Its safety and effectiveness in younger populations have not been established, but it is expected to have similar effects in adolescents aged 12 and older who weigh at least 88 pounds.

• Geriatric Use: In the CANOPY trial, 25 percent of participants were 65 or older, and age had no significant impact on Pemivibart's pharmacokinetics.

• Renal Impairment: Pemivibart is not removed from the body through urine, so kidney problems are not expected to affect its exposure.

• Hepatic Impairment: The impact of liver impairment on Pemivibart's pharmacokinetics is not known.