pemgarda

1 EMERGENCY USE AUTHORIZATION FOR 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 se…

2 DOSAGE AND ADMINISTRATION 2.1 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 [see Clinical Pharmacology (1 2.3 ) ]. 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 [see Clinical Pharmacology (12.3 ) , Microbiology ( 12.4 ), and Clinical Studies ( 14 ) ] . 2.2 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 [see Use in Specific Populations ( 8 ) ] . 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℃ [64℉ to 79℉]) 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 (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 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 [see Warnings and Precautions ( 5.1 ) ] . 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 Warnings and Precautions (5.1 ) ] . 2.1 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 [see Clinical Pharmacology (1 2.3 ) ]. 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 PE…

5 WARNINGS AND PRECAUTIONS 5.1 Anaphylaxis Anaphylaxis has been observed with PEMGARDA in 4 of 623 (0.6%) participants in a clinical trial [see Adverse Reactions (6.1 )] . 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 [see Adverse Reactions (6.1 ), and Clinical Studies (14 )] . 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 [see Contraindications (4 )] . 5.2 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. 5.3 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 [see Description (11 ) ] . 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. 5.4 Risk for COVID-19 Due to SARS-CoV-2 Viral Variants with Substantially Reduced Susceptibility to PEMGARDA Certain SARS-CoV-2 viral variants may em…

4 CONTRAINDICATIONS PEMGARDA is contraindicated in individuals with previous severe hypersensitivity reactions, including anaphylaxis, to any component of PEMGARDA.

7 DRUG INTERACTIONS 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 [see Clinical Pharmacology (12.3 )] .

6 ADVERSE REACTIONS To report SERIOUS ADVERSE REACTIONS or MEDICATION ERRORS potentially related to PEMGARDA (1) do so by submitting FDA Form 3500 online, (2) by downloading this form, and then submitting it by mail or fax, or (3) 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: pv@invivyd.com or call 1-800-890-3385 to report adverse events. 6.1 Adverse Reactions from Clinical Studies The following adverse reactions have been observed in the clinical study of PEMGARDA that supported the EUA [see Clinical Studies (14 )] . 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 reac…