Pemgarda Drug Information
Generic name: PEMIVIBART
Uses of Pemgarda
The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the emergency use of the unapproved product PEMGARDA (pemivibart) 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 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/mm 3, 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) Limitations of Authorized Use PEMGARDA is not authorized for use: -For 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. PEMGARDA is authorized for use only when the combined national frequency of variants with substantially reduced susceptibility to PEMGARDA is less than or equal to 90%, based on available information including variant susceptibility to PEMGARDA and national variant frequencies FDA will monitor conditions to determine whether use is consistent with the scope of authorization, referring to available information, including information on variant susceptibility (e.g., Section 12.4 of the authorized Fact Sheet for Healthcare Providers) and CDC variant frequency data available at: https://covid.cdc.gov/covid-data-tracker/#variant-proportions.. Pre-exposure prophylaxis with PEMGARDA 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, PEMGARDA should be administered at least 2 weeks after vaccination. PEMGARDA may only be prescribed for an individual patient by physicians, advanced practice registered nurses, and physician assistants that are licensed or authorized under State law to prescribe drugs. PEMGARDA has been authorized by FDA for the emergency use described above.
PEMGARDA is not FDA-approved for any use, including use for pre-exposure prophylaxis of COVID-19. PEMGARDA is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of PEMGARDA under section 564(b) of the FD&C Act, 21 U.S.C. § 360bbb-3(b), unless the authorization is terminated or revoked sooner. Justification for Emergency Use of Drugs During the COVID‑19 Pandemic: There is currently an outbreak of coronavirus disease 2019 (COVID‑19) caused by SARS‑CoV‑2, a novel coronavirus. The Secretary of the U.S. Department of Health and Human Services (HHS) has: Determined that there is a public health emergency, or significant potential for a public health emergency See U.S. Department of Health and Human Services, Determination of a Public Health Emergency and Declaration that Circumstances Exist Justifying Authorizations Pursuant to Section 564(b) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3. February 4, 2020; https://www.federalregister.gov/documents/2020/02/07/2020-02496/determination-of-public-health-emergency.
See also U.S. Department of Health and Human Services, Amended Determination of a Public Health Emergency or Significant Potential for a Public Health Emergency Pursuant to Section 564(b) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3(b). March 15, 2023 (“Amended Determination”); https://www.federalregister.gov/documents/2023/03/20/2023-05609/covid-19-emergency-use-authorization-declaration.. Declared that circumstances exist justifying the authorization of emergency use of drugs and biological products for the prevention or treatment of COVID-19 See U.S. Department of Health and Human Services, Declaration that Circumstances Exist Justifying Authorizations Pursuant to Section 564(b) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3, 85 FR 18250 (April 1, 2020); https://www.federalregister.gov/documents/2020/04/01/2020-06905/emergency-use-authorization-declaration. See also Amended Determination (“The declarations issued pursuant to section 564(b) of the FD&C Act that circumstances exist justifying the authorization of emergency use of certain in vitro diagnostics, personal respiratory protective devices, other medical devices and drugs and biological products, as set forth in those declarations, and that are based on the February 4, 2020 determination, remain in effect until those declarations are terminated in accordance with section 564 of the FD&C Act.”).. An EUA is an FDA authorization for the emergency use of an unapproved product or unapproved use of an approved product (i.e., drug, biological product, or device) in the United States under certain circumstances including, but not limited to, when the Secretary of HHS declares that there is a public health emergency that affects the national security or the health and security of United States citizens living abroad, and that involves biological agent(s) or a disease or condition that may be attributable to such agent(s). Criteria for issuing an EUA include: The biological agent(s) can cause a serious or life-threatening disease or condition. Based on the totality of the available scientific evidence (including data from adequate and well controlled clinical trials, if available), it is reasonable to believe that: the product may be effective in diagnosing, treating, or preventing the serious or life-threatening disease or condition; and the known and potential benefits of the product - when used to diagnose, prevent, or treat such disease or condition - outweigh the known and potential risks of the product, taking into consideration the material threat posed by the biological agent(s). There is no adequate, approved, and available alternative to the product for diagnosing, preventing, or treating the serious or life-threatening disease or condition.
Information Regarding Available Alternatives for the EUA Authorized Use There are no adequate, approved, and available alternatives to PEMGARDA for the pre-exposure prophylaxis of COVID-19 in individuals who are unlikely to mount an adequate immune response to COVID-19 vaccination. For information on clinical studies of PEMGARDA and other therapies for the pre-exposure prophylaxis of COVID-19, see www.clinicaltrials.gov.
Dosage & Administration of Pemgarda
Dosage for Emergency Use of
PEMGARDA Initial Dosing : The initial dosage of PEMGARDA in adults and adolescents (12 years of age and older weighing at least 40 kg) is 4500 mg administered as a single intravenous (IV) infusion. Repeat Dose : The repeat dosage is 4500 mg of PEMGARDA administered as a single IV infusion every 3 months. Repeat dosing should be timed from the date of the most recent PEMGARDA dose.
The recommendations for dosing are based on the totality of the scientific evidence including clinical pharmacology data, antiviral activity data, and clinical study data .
Dosage Adjustment in Specific Populations No dosage adjustment is recommended in pregnant
or lactating individuals, in geriatrics, or in individuals with renal or hepatic impairment . 2.3Dose Preparation and Administration General Information : PEMGARDA should be prepared and administered by a qualified healthcare provider using aseptic technique. Vials of PEMGARDA are for one-time use only. Visually inspect the vials for particulate matter and discoloration.
PEMGARDA is a clear to slightly opalescent, colorless to yellow solution. Discard the vial if the solution is cloudy, discolored, or if visible particles are observed. PEMGARDA should be administered as an IV infusion diluted with 0.9% sodium chloride.
Materials Needed: 9 single-dose vials of PEMGARDA (125 mg/mL) 50 mL prefilled bag of 0.9% sodium chloride (normal saline) for IV injection IV extension set with inline 0.2-micron filter Infusion pump or gravity infusion set 0.9% sodium chloride injection for flushing Preparation : Remove PEMGARDA 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.
Inspect the 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 PEMGARDA from nine 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 PEMGARDA and 14 mL of 0.9% sodium chloride. This product is preservative-free and therefore should be administered 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. Administration: PEMGARDA should only be administered 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 . 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 .
Side Effects of Pemgarda
Adverse Reactions from Clinical Studies
The following adverse reactions have been observed in the clinical study of PEMGARDA that supported the EUA . The adverse reaction rates observed in the clinical study cannot be directly compared to rates in the clinical studies of other products and may not reflect the rates observed in clinical practice. Additional adverse reactions associated with PEMGARDA may become apparent with more widespread use. The safety of PEMGARDA is based on exposure of 623 participants who received at least one dose of PEMGARDA 4500 mg IV in one of two cohorts in the ongoing CANOPY trial.
Cohort A is a single-arm, open-label trial in adults who have moderate-to-severe immune compromise (n=306), while Cohort B is a randomized, placebo-controlled trial in which adults who do not have moderate-to-severe immune compromise received PEMGARDA (n=317) or placebo (n=162). In Cohort A, 297 participants received a second dose of PEMGARDA 4500 mg IV three months after the initial dose. In Cohort B, 296 participants received a second dose of PEMGARDA 4500 mg IV and 154 received a second dose of placebo three months after the initial dose. Anaphylaxis Anaphylaxis was observed in 4 of 623 (0.6%) participants in CANOPY, all in Cohort A. Two participants had anaphylaxis during the first infusion, and two participants had anaphylaxis during the second infusion.
All four reactions led to permanent discontinuation of PEMGARDA. Three participants had complete resolution, and one participant had acute resolution with sequelae related to a flare of an underlying condition. Symptoms of anaphylaxis during the first dose included dyspnea, diaphoresis, erythema (face), chest discomfort, and tachycardia in one participant, and flushing, dizziness, tinnitus, and wheezing in one participant. Treatment for both included diphenhydramine.
Both instances of anaphylaxis with the second dose were reported as life-threatening. Symptoms during the second infusion and following discontinuation of the infusion in both participants included pruritus, urticaria, angioedema, dyspnea, and either erythema or flushing. One participant also experienced headache, dizziness, and chest pain; additionally, pruritus, erythema, and urticaria reoccurred in this participant within 24 hours of the initial onset of anaphylaxis.
Both participants were treated with diphenhydramine and epinephrine, and one participant also received oral prednisone and metoprolol for an associated flare of an underlying condition. Systemic Infusion-Related Reactions and Hypersensitivity Reactions First Dose Systemic infusion-related reactions and hypersensitivity reactions (i.e., adverse events assessed as causally related) were observed with the first dose in CANOPY in 4% (24/623) of participants who received PEMGARDA across cohorts, including: 7% (20/306) of participants who have moderate-to-severe immune compromise (Cohort A), and 1% (4/317) of participants who received PEMGARDA in Cohort B Infusion-related reactions and hypersensitivity reactions were not observed in any participants who received placebo in Cohort B. Systemic infusion-related or hypersensitivity reactions that started within 24 hours of the first dose of PEMGARDA treatment were reported as infusion-related reaction, infusion-related hypersensitivity, hypersensitivity, fatigue, headache, tachycardia, dermatitis, diarrhea, myalgia, nausea, paresthesia, presyncope, and tremor. All reactions were mild or moderate, but two reactions were anaphylaxis . Infusion-related reactions or hypersensitivity reactions led to discontinuation of the first infusion in 1% (6/623) of participants who received PEMGARDA. First and Second Dose, Cumulative Cumulatively, infusion-related reactions and hypersensitivity reactions were observed in 6% (38/623) of participants across cohorts, including: 9% (27/306) of participants who have moderate-to-severe immune compromise (Cohort A). 3% (11/317) of participants who received PEMGARDA in Cohort B. The severity of the reactions was generally mild (24/38) or moderate (12/38), but two reactions, both in Cohort A, were life-threatening . Infusion-related reactions or hypersensitivity reactions led to discontinuation of the first or second infusion in 1% (10/623) of participants who received PEMGARDA across cohorts, including: 2% (7/306) of participants who have moderate-to-severe immune compromise (Cohort A). 1% (3/317) of participants who received PEMGARDA in Cohort B. Cumulatively, infusion-related reactions and hypersensitivity reactions were observed following both the first and second dose of PEMGARDA in 1% (7/623) of participants who received PEMGARDA across cohorts, including: 2% (6/306) of participants who have moderate-to-severe immune compromise (Cohort A). <1% (1/317) of participants who received PEMGARDA in Cohort B. Local Infusion Site Reactions First and Second Dose, Cumulative Cumulatively, local infusion site reactions were observed in 2% (6/306) of participants who have moderate-to-severe immune compromise (Cohort A) with either the first or second dose of PEMGARDA. No local infusion site reactions were observed in Cohort B. Local reactions were reported as infusion site bruising, infusion site erythema, and injection site reaction.
All local reactions were mild, and none led to treatment discontinuation. Cumulatively, infusion site infiltration or extravasation was noted in 5% (15/306) of participants who have moderate-to-severe immune compromise (Cohort A) and in 1% (3/317) of participants in Cohort B with either the first or second dose of PEMGARDA. Other Common Adverse Events First and Second Dose, Cumulative In addition to systemic and local infusion-related/hypersensitivity reactions described above, the most common (≥2%) treatment-emergent adverse events, irrespective of causality, observed with PEMGARDA through Month 6 were as follows: In participants who have moderate-to-severe immune compromise in Cohort A: viral infection (7%), upper respiratory tract infection (7%), influenza-like illness (4%), urinary tract infection (4%), fatigue (3%), headache (3%), sinusitis (3%), nasopharyngitis (2%), influenza (2%), and pneumonia (2%). In Cohort B: upper respiratory tract infection (8%), viral infection (6%), influenza-like illness (5%), enterovirus infection (3%), and viral upper respiratory tract infection (2%). These adverse events were observed at a similar or higher rate with placebo. Cumulatively, infusion site infiltration or extravasation was noted in 5% (15/306) of participants who have moderate-to-severe immune compromise (Cohort A) and in 1% (3/317) of participants in Cohort B with either the first or second dose of PEMGARDA. To report SERIOUS ADVERSE REACTIONS or MEDICATION ERRORS potentially related to PEMGARDA by submitting FDA Form 3500 online, by downloading this form, and then submitting it by mail or fax, or by contacting the FDA at 1-800-332-1088 to request this form.
To report suspected adverse reactions, please also provide a copy of this form to Invivyd, Inc. by email at: [email protected] or call 1-800-890-3385 to report adverse events.
Required Reporting for Serious Adverse Events and Medication Errors
The prescribing healthcare provider and/or the provider’s designee is/are responsible for mandatory reporting of all serious adverse events* and medication errors potentially related to PEMGARDA within 7 calendar days from the healthcare provider’s awareness of the event, using FDA Form 3500 (for information on how to access this form, see below). The FDA requires that such reports, using FDA Form 3500, include the following: Patient demographics and baseline characteristics (e.g., patient identifier, age or date of birth, sex, weight, ethnicity, and race). A statement “PEMGARDA use for the pre-exposure prophylaxis of COVID-19 under Emergency Use Authorization (EUA)” under the “Describe Event, Problem, or Product Use/Medication Error” heading. Information about the serious adverse event or medication error (e.g., signs and symptoms, test/laboratory data, complications, timing of drug initiation in relation to the occurrence of the event, duration of the event, treatment required to mitigate the event, evidence of event improvement/disappearance after stopping or reducing the dosage, evidence of event reappearance after reintroduction, clinical outcomes). Patient’s preexisting medical conditions and use of concomitant products. Information about the product (e.g., dosage, route of administration, NDC #). Submit serious adverse event and medication error reports using FDA Form 3500 to FDA MedWatch using one of the following methods: Complete and submit the report online: www.fda.gov/medwatch/report.htm.
Complete and submit a postage-paid FDA Form 3500 ( https://www.fda.gov/media/76299/download ) and return by: Mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787, or Fax to 1-800-FDA -0178, or Call 1-800-FDA -1088 to request a reporting form. In addition, please provide a copy of all FDA MedWatch forms to: Invivyd, Inc. Email: [email protected] Or call Invivyd, Inc. at 1-800-890-3385 to report serious adverse events.
The prescribing healthcare provider and/or the provider’s designee is/are responsible for mandatory responses to requests from FDA for information about serious adverse events and medication errors following receipt of PEMGARDA. *Serious adverse events are defined as: Death A life-threatening adverse event Inpatient hospitalization or prolongation of existing hospitalization A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions A congenital anomaly/birth defect Other important medical events, which may require a medical or surgical intervention to prevent death, a life-threatening event, hospitalization, disability, or congenital anomaly To report SERIOUS ADVERSE REACTIONS or MEDICATION ERRORS potentially related to PEMGARDA do so by submitting FDA Form 3500 online, by downloading this form, and then submitting it by mail or fax, or by contacting the FDA at 1-800-332-1088 to request this form. To report suspected adverse reactions, please also provide a copy of this form to Invivyd, Inc. by email at: [email protected] or call 1-800-890-3385 to report adverse events.
Warnings & Cautions for Pemgarda
Anaphylaxis Anaphylaxis has been observed with
PEMGARDA 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, PEMGARDA was permanently discontinued. Prior to administering PEMGARDA, consider the potential benefit of COVID-19 prevention along with the risk of anaphylaxis . Administer PEMGARDA 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 two 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 PEMGARDA 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 PEMGARDA. 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., pre-syncope, 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 two 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 PEMGARDA 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 PEMGARDA administration. Administration of PEMGARDA 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 PEMGARDA, immediately discontinue administration and initiate appropriate medications and/or supportive care.
Clinically monitor individuals after infusion and observe for at least two hours.
Risk for
COVID-19 Due to SARS-CoV-2 Viral Variants with Substantially Reduced Susceptibility to PEMGARDA Certain SARS-CoV-2 viral variants may emerge that have substantially reduced susceptibility to PEMGARDA. PEMGARDA may not be effective at preventing COVID-19 caused by these SARS‑CoV-2 viral variants. The cell culture neutralization activity of PEMGARDA against SARS-CoV-2 viral variants is described in Microbiology. Inform individuals of the increased risk, compared to other variants, for COVID-19 due to emergent SARS-CoV-2 viral variants that exhibit substantially reduced susceptibility to PEMGARDA. 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. For additional information on the symptoms of COVID-19, please see https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html.
Drug Interactions with Pemgarda
Drug-drug interaction studies have not been performed. PEMGARDA is not renally excreted or metabolized by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are renally excreted or that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely .
Contraindications for Pemgarda
is contraindicated in individuals with previous severe hypersensitivity reactions, including anaphylaxis, to any component of PEMGARDA.
Overdosage Information for Pemgarda
Doses above 4500 mg PEMGARDA (the authorized dose of pemivibart) were not administered in clinical studies. There is no specific treatment for overdose with PEMGARDA.
Clinical Studies of Pemgarda
Overview of Immunobridging Approach To support this
EUA, an immunobridging approach was used to determine if PEMGARDA may be effective for pre-exposure prophylaxis of COVID-19. Immunobridging is based on the serum neutralization titer-efficacy relationships identified with other neutralizing human monoclonal antibodies against SARS-CoV-2. This includes adintrevimab, the parent mAb of pemivibart, and other mAbs that were previously authorized for EUA. To support immunobridging, serum neutralization titer was utilized to compare PEMGARDA to previous mAbs.
Pre-exposure Prophylaxis of
COVID-19 (VYD222-PREV-001 ) CANOPY is a clinical trial that evaluated PEMGARDA for the pre-exposure prophylaxis of COVID-19 in adults ≥18 years of age in two cohorts. Cohort A: single-arm, open-label trial in adults who have moderate-to-severe immune compromise. Cohort B: placebo-controlled, randomized trial in adults who do not have moderate-to-severe immune compromise.
A total of 623 participants, 306 in Cohort A and 317 in Cohort B, received at least one dose of PEMGARDA 4500 mg in the trial. A total of 297 participants in Cohort A and 296 participants in Cohort B received a second dose of PEMGARDA 4500 mg at Month 3 redosing. Of the 162 participants who received the initial dose of placebo in Cohort B, 154 participants received a second dose of placebo at Month 3 redosing.
The trial excluded participants with known or suspected SARS-CoV-2 infection within 120 days before randomization or a positive SARS-CoV-2 antigen test or RT-PCR at the time of screening. The primary data to support this EUA comes from Cohort A and is summarized below. Participants in Cohort A were mostly female (61%), White (86%) or Black/African American (12%), and not Hispanic or Latino (94%). The median age was 59 years, with 31% aged 65 years or older.
All participants had underlying moderate-to-severe immune compromise, including: 65% taking high-dose corticosteroids/other immunosuppressive medications 13% acute leukemia, chronic lymphocytic leukemia, non-Hodgkin, lymphoma, or multiple myeloma (regardless of treatment) 12% primary immunodeficiency 11% solid organ transplant recipient 9% advanced HIV infection 7% actively treated for solid tumor or hematologic malignancies Immunobridging Results The primary efficacy objective of Cohort A was to evaluate protection against symptomatic COVID-19 based on calculated titers against SARS-CoV-2 following PEMGARDA administration by immunobridging to historical data from the EVADE study, which provided evidence of clinical efficacy of adintrevimab, the parent mAb of pemivibart. The primary immunobridging endpoint for Cohort A compared the ratio of the geometric mean titers between pemivibart against the relevant variant (JN.1) at Day 28 to the reference titer at Day 28. The reference titer at Day 28 was the extrapolated titer from the Day 90 adintrevimab titer using the half-life of pemivibart. Immunobridging would be established if the lower limit of the 2-sided 90% CI of the ratio of the geometric mean titer value is greater than 0.8. The immunobridging results are as follows: the geometric mean ratio between the calculated titer for pemivibart against JN.1 (based on a pseudotyped VLP neutralization assay EC50 value of 74.6 ng/mL) and the calculated titer for adintrevimab against Delta (based on an authentic virus neutralization assay EC50 value of 7 ng/mL) was 0.70 (90% CI: 0.68-0.72). However, there are limitations of this analysis, including differences in the methodologies of the assays used to determine the EC50 values for pemivibart and adintrevimab against the respective variants.
In an analysis using an identical cell-based assay (a pseudotyped VLP neutralization assay), for the calculated titer comparison between pemivibart against JN.1 (based on an EC50 value of 74.6 ng/mL) and adintrevimab against Delta (based on an EC50 value of 3.5 ng/mL), the geometric mean ratio was 0.35 (90% CI: 0.34-0.36).This analysis highlights the impact of even modest differences in EC50 values on the results of the primary endpoint. In a supplementary immunobridging analysis, the titer values of pemivibart against JN.1 were compared, using published literature, to the titers associated with efficacy of three other SARS-CoV-2 targeting mAbs in prior clinical trials. The range of titers achieved with pemivibart for 3 months following administration of 4500 mg IV were consistent with the titer levels associated with clinical efficacy in prior clinical trials evaluating certain monoclonal antibodies for the prevention of COVID-19. Exploratory Clinical Efficacy Results An exploratory efficacy objective of Cohort B was to evaluate clinical efficacy of PEMGARDA compared to placebo in the prevention of RT-PCR-confirmed COVID-19 in randomized participants without SARS-CoV-2 infection at baseline and without moderate-to-severe immune compromise.
Table 3 provides the results for the Cohort B exploratory clinical efficacy endpoint. Most infection events occurred during a period of time when JN.1 and variants with similar susceptibilities were dominant. No deaths or COVID-19-related hospitalizations occurred in either treatment arm of Cohort B through Month 6. PEMGARDA is not authorized for use in individuals who do not have moderate-to-severe immune compromise.
Table 3. Exploratory Clinical Efficacy Results in Randomized Participants without SARS-CoV-2 Infection at Baseline in CANOPY Cohort B (Adults who do not have Moderate-to-Severe Immune Compromise) PEMGARDA n=317 Placebo n=160 RT-PCR-confirmed symptomatic COVID-19, COVID-19-related hospitalization, or all-cause death a through Month 3 b Proportion: n (%) 1 8 Standardized Relative Risk Reduction (95% CI) 94% (50%, 99%) RT-PCR-confirmed symptomatic COVID-19, COVID-19-related hospitalization, or all-cause deatha through Month 6 c Proportion: n (%) 6 19 Standardized Relative Risk Reduction (95% CI) 84% (61%, 94%) a No COVID-19-related hospitalizations or deaths occurred in either treatment arm of Cohort B through Month 6. b Following the initial dosing period of the trial c Cumulative through Month 6, following the initial dosing and redosing periods of the trial An exploratory objective of Cohort A was to collect data on RT-PCR-confirmed COVID-19, COVID-19-related hospitalizations, or all-cause death in participants who received a full initial dose of study drug. Table 4 provides these results for Cohort A. No COVID-19-related hospitalizations occurred in Cohort A through Month 6. Two all-cause deaths (one due to an unknown cause and one due to suicide) occurred in Cohort A through Month 6. Table 4. Rates of RT-PCR-confirmed COVID-19, COVID-19-Related Hospitalizations, or All-Cause Death in Participants in CANOPY Cohort A (Adults who have Moderate-to-Severe Immune Compromise) PEMGARDA n=298 RT-PCR-confirmed symptomatic COVID-19, COVID-19-related hospitalization, or all-cause death a through Month 3 b Proportion: n (%) 3 RT-PCR-confirmed symptomatic COVID-19, COVID-19-related hospitalization, or all-cause deatha through Month 6 c Proportion: n (%) 11 a No COVID-19-related hospitalizations occurred in Cohort A through Month 6. Two all-cause deaths (one due to an unknown cause and one due to suicide) occurred in Cohort A through Month 6. b Following the initial dosing period of the trial c Cumulative through Month 6, following the initial dosing and redosing periods of the trial
Overall Benefit-Risk Assessment and Limitations of Data Supporting the Benefits of the
Product Based on the totality of scientific evidence available, it is reasonable to believe that PEMGARDA may be effective for pre-exposure prophylaxis of COVID-19 caused by susceptible SARS-CoV-2 variants in the authorized population . The calculated pemivibart serum neutralizing antibody titers for the JN.1 variant were consistent with the titer levels associated with efficacy in prior clinical trials of adintrevimab and certain other monoclonal antibody products previously authorized for the prevention of COVID-19. The exploratory clinical results from Cohort B of CANOPY also provide support that PEMGARDA may be effective for pre-exposure prophylaxis of COVID-19 caused by the JN.1 variant and other similarly susceptible SARS-CoV-2 variants in the authorized use population. There are limitations of the immunobridging data supporting the benefits of PEMGARDA. Evidence of clinical efficacy for other neutralizing human monoclonal antibodies against SARS-CoV-2 was based on different populations and SARS-CoV-2 variants that are no longer circulating. Additionally, the variability associated with cell-based EC 50 value determinations across laboratories, along with limitations related to PK data and efficacy estimates for the mAbs in prior clinical trials, impact the ability to precisely estimate protective titer ranges.
The potential benefits of PEMGARDA for pre-exposure prophylaxis of COVID-19 caused by variants other than JN.1 may vary based on variant susceptibility and national variant frequencies. The totality of scientific evidence, including the available clinical and pharmacokinetic data along with the nonclinical viral neutralization data provided from Monogram in Microbiology, support the potential benefit of PEMGARDA in the authorized patient population.
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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