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. com or call 1-800-890-3385 to report adverse events. 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.
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.
, 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.
2 )] . 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. 2 )] . 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 (1) 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. com or call 1-800-890-3385 to report adverse events. 4 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).
, 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.
, 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. , dosage, route of administration, NDC #). htm . gov/media/76299/download ) and return by: Mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787, or Fax to 1-800-FDA (332)-0178, or Call 1-800-FDA (332)-1088 to request a reporting form.
In addition, please provide a copy of all FDA MedWatch forms to:
Invivyd, Inc. com 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 (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. com or call 1-800-890-3385 to report adverse events. 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.
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.
, 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.
2 )] . 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. 2 )] . 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 (1) 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. com or call 1-800-890-3385 to report adverse events. 4 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).
, 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.
, 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. , dosage, route of administration, NDC #). htm . gov/media/76299/download ) and return by: Mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787, or Fax to 1-800-FDA (332)-0178, or Call 1-800-FDA (332)-1088 to request a reporting form.
In addition, please provide a copy of all FDA MedWatch forms to:
Invivyd, Inc. com 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 (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. com or call 1-800-890-3385 to report adverse events.