PALFORZIA had a consistent and established safety profile in toddlers (aged 1–3 years)¹

The most common side effects

The most common treatment-emergent adverse reactions in ≥5% of those taking PALFORZIA (n=87) were cough, sneezing, rhinitis, nasal congestion, throat irritation, wheezing, abdominal pain, vomiting, diarrhea, oral pruritus, oropharyngeal pain, urticaria, rash, pruritus, and perioral dermatitis.¹

POSEIDON clinical study summary of TEAEs and anaphylactic reactions

In the POSEIDON study, anaphylactic reaction was reported in 8 (8.2%) PALFORZIA-treated subjects (in no subjects during Initial Dose Escalation, 2 subjects during Up-Dosing, and 6 subjects during Maintenance) and 4 (8.3%) placebo-treated subjects (in no subjects during Initial Dose Escalation, 2 subjects during Up-Dosing, and 2 subjects during Maintenance). Of the 9 anaphylactic reactions reported, in 8 children receiving PALFORZIA, only 3 were attributed to PALFORZIA, all occurring during the Up-Dosing phase. The remaining 6 reactions were due to exposure to other food allergens.¹

 
*Anaphylactic reactions were graded as Mild (skin and subcutaneous issues, gastrointestinal and/or mild respiratory), Moderate (mild symptoms + features suggesting moderate respiratory, cardiovascular, or gastrointestinal symptoms), or Severe (hypoxia, hypotension, or neurological compromise).^3
†Most anaphylactic reactions were related to non-peanut food allergen exposure. Anaphylactic reactions by events: 13 anaphylactic reaction events (9 PALFORZIA, 4 placebo); 10 related to other food allergen exposure (6 PALFORZIA, 4 placebo); none related to accidental peanut exposure.^1,2
‡Total percentage does not equal the sum of Mild and Moderate reactions because 1 subject experienced 2 related anaphylactic reactions (1 Mild and 1 Moderate).^3
§PALFORZIA: 3 subjects with viral infections, 2 subjects with asthma, 1 subject with viral infection and asthma; placebo: 1 subject with asthma, 1 subject with carbon monoxide poisoning.^3
¶No eosinophilic esophagitis.³

Treatment-emergent adverse reactions in ≥5% of 
PALFORZIA-treated subjects (aged 1 through 3 years)^1,3

Treatment-emergent adverse reactions are included in the table if they occurred in ≥5% of PALFORZIA-treated subjects across all dosing phases combined. Data across all dosing phases combined are not shown.

At each level of summarization (any event, system organ class, and preferred term), subjects with more than one adverse reaction were counted only once within study period.

[1] Adverse reactions were coded to system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA), version 21.1. [2] Includes preferred terms of rhinorrhea, rhinitis, and rhinitis allergic. [3] Includes preferred terms of wheezing and stridor. [4] Includes preferred term of abdominal pain, abdominal pain upper, and abdominal discomfort. [5] Includes preferred terms of vomiting and regurgitation. [6] Includes preferred terms of diarrhea and frequent bowel movements. [7] Includes preferred terms of oral pruritus, tongue pruritis, and lip pruritus. [8] Includes preferred terms of oropharyngeal pain, oral discomfort, odynophagia, and oral pain. [9] Includes preferred terms of urticaria and urticaria papular. [10] Includes preferred terms of rash, rash erythematous, rash generalized, rash macular, rash papular, rash pruritic, eczema, erythema, and papule. [11] Includes preferred terms of pruritus, pruritus generalized, ear pruritus, eye pruritus, and nasal pruritus.

A total of 15 (15.3%) PALFORZIA-treated subjects and 3 (6.3%) placebo-treated subjects discontinued for any reason in the POSEIDON study. Adverse reactions led to study discontinuation in 5.1% of PALFORZIA-treated subjects and no placebo-treated subjects during Up-Dosing in the POSEIDON study, and 2.3% PALFORZIA-treated subjects and no placebo-treated subjects during Maintenance dosing.¹

Gastrointestinal reactions were the most common reason leading to discontinuation of study product during Up-Dosing (3.1% PALFORZIA, none in placebo), followed by respiratory disorders (3.1% PALFORZIA, none in placebo) in the POSEIDON study. No PALFORIZA-treated subjects discontinued during IDE.¹
 

Comparison of maximum severity of symptoms at any challenge dose^2#

^#At each level of summarization (any event, system organ class, or preferred term), participants with more than one AE related to trial product were counted only once within each trial period. Values in bold indicate AEs with 5 higher incidence in the PALFORZIA group than in the placebo group.
^∆There were ≥20% of participants in either treatment group with a ≥5% higher incidence in the PALFORZIA group.

**Systemic allergic reactions were defined as anaphylactic reaction of any severity.

The maximum severity of symptoms at any exit challenge dose was predominately none to mild for PALFORZIA-treated participants and mild to moderate for placebo-treated participants.²

No participant had symptoms considered life threatening or fatal.²

PALFORZIA had a consistent and established safety profile in children (aged 4–17 years)¹

The most common side effects

The most common treatment-emergent adverse reactions in ≥5% of those taking PALFORZIA (n=372) were abdominal pain, vomiting, nausea, oral pruritus, oral paresthesia, throat irritation, cough, rhinorrhea, sneezing, throat tightness, wheezing, dyspnea, pruritus, urticaria, anaphylactic reactions, and ear pruritus.¹

Comparison of the maximum severity of symptoms at any challenge dose of peanut protein during the exit DBPCFC.¹

5% of participants treated with PALFORZIA experienced severe symptoms compared with 10.5% of those given placebo, during the exit DBPCFC.¹

5% of participants treated with PALFORZIA experienced severe symptoms compared with 10.5% of those given placebo, during the exit DBPCFC.¹

*Participants without an exit DBPCFC were assigned the maximum severity during the screening DBPCFC, which equates to no change from screening. P-value <0.0001; symptom severity was assigned with equally spaced scores (e.g., 0, 1, 2, and 3 for none, mild, moderate, and severe, respectively), and the difference of mean scores between the two treatment arms was tested using the Cochran-Mantel-Haenszel statistic stratified by geographic region (North America, Europe).^1
†Includes severe symptoms and life-threatening or fatal reactions. No participants had symptoms considered life threatening or fatal.¹

Anaphylactic reactions (pooled data)

In PALFORZIA safety data, anaphylactic reaction includes systemic allergic reactions of any severity:¹

Severe anaphylaxis was reported in 0.6% of participants (4/709) during Up-Dosing and in 0.3% of participants (1/310) during Maintenance dosing across studies.¹

^‡Data was pooled across two phase 3 clinical trials of participants ages 4 through 17 years. (Study 1-PALISADE), (Study 2-RAMSES).

Most frequently reported adverse reactions in participants aged 4 through 17 years (pooled data across two phase 3 clinical trials)^1§¶  

The majority of adverse reactions were mild to moderate and were more frequently reported during the Up-Dosing and decreased during Maintenance dosing.^1,4

Symptoms during in-office PALFORZIA dosing had a median time to onset of 4 minutes for 71% of participants. Median time to resolution was 37 minutes.¹

At each level of summarization (any event, system organ class, or preferred term), participants with more than one adverse reaction were counted only once within each study period.^1
§TEAEs reported in ≥5% of participants treated with PALFORZIA and ≥5% percentage points were greater than reported in participants treated with placebo in any dosing phase (aged 4 through 17 years).
^¶AEs were coded to system organ class and preferred term using the MedDRA, version 19.1. In RAMSES, no adverse events ≥5% were reported in participants following treatment with 300 mg PALFORZIA (n=265).^1
#Study 1 (PALISADE) was a randomized, double-blind, placebo-controlled efficacy and safety study conducted in the United States, Canada, and Europe evaluating PALFORZIA vs placebo in 496 participants aged 4-17 years with peanut allergy. Participants were Up-Dosed for 20 to 40 weeks followed by Maintenance dosing for 24 to 28 weeks.^1,3
ΔStudy 2 (RAMSES) was a randomized, double-blind, placebo-controlled safety study conducted in the United Staes and Canada evaluating PALFORZIA vs placebo in 506 participants aged 4 through 17 with peanut allergy. Participants were Up-Dosed for 20 to 40 weeks up to 300 mg daily dose with no extended Maintenance dosing.^1
**Includes preferred terms of abdominal pain, abdominal pain upper, and abdominal discomfort.^1
††Includes preferred terms of oral pruritus, tongue pruritus, and lip pruritus.^1
‡‡The anaphylactic reaction preferred term includes systemic allergic reactions of any severity, or which severe anaphylaxis was reported in four PALFORZIA-treated participants (0.6%) during Up-Dosing and one PALFORZIA-treated participant (0.3%) during Maintenance dosing.¹

Percentage of patient-reported TEAEs and severity over time (pooled data)⁴

PALFORZIA safety continued to improve over time (Pooled safety analysis of patients aged 4–17 years from 6 PALFORZIA clinical trials)⁴

Adapted from: Bird JA, et al. 2023.⁴

From a pooled safety analysis from six PALFORZIA clinical trials and three open-label extension studies to describe additional long-term pooled safety data from baseline through approximately 5 years of treatment.⁴

In children and adolescents, continued daily treatment with PALFORZIA beyond 1 year has demonstrated an acceptable safety profile with continued and improved efficacy.⁵

The safety profile of PALFORZIA improved over time³

Overall summary of treatment-emergent adverse events (integrated safety population; N=351)⁶

^§§Participants in cohorts 3B and 3C underwent initial daily dosing for 28 weeks.^6
¶¶Participants with >1 AE were counted only once using the highest severity and closest relationship to study product.^6
##Exposure-adjusted event rates were defined as the total number of events divided by the total number of participant-years at risk during the period.⁶

Safety data presented below is pooled data across two phase 3 clinical trials in ages 4 through 17 years¹

In Studies 1 and 2:

Study 1 (PALISADE) was a randomized, double-blind, placebo-controlled efficacy and safety study conducted in the United States, Canada, and Europe evaluating PALFORZIA vs placebo in 496 participants aged 4-17 years with peanut allergy. Participants were Up-Dosed for 20 to 40 weeks followed by Maintenance dosing for 24 to 28 weeks.

Study 2 (RAMSES) was a randomized, double-blind, placebo-controlled safety study conducted in the United Staes and Canada evaluating PALFORZIA vs placebo in 506 participants aged 4 through 17 with peanut allergy. Participants were Up-Dosed for 20 to 40 weeks up to 300 mg daily dose with no extended Maintenance dosing.

Most frequently reported adverse reactions in participants aged 4 through 17 years^1*†

The majority of adverse reactions were mild to moderate and were more frequently reported during the Up-Dosing and decreased during Maintenance dosing.^1,4

Symptoms during in-office PALFORZIA dosing had a median time to onset of 4 minutes for 71% of participants. Median time to resolution was 37 minutes.¹

At each level of summarization (any event, system organ class, or preferred term), participants with more than one adverse reaction were counted only once within each study period.

*TEAEs reported in ≥5% of participants treated with PALFORZIA and ≥5% percentage points were greater than reported in participants treated with placebo in any dosing phase (aged 4 through 17 years).^1
†AEs were coded to system organ class and preferred term using the MedDRA, version 19.1. In RAMSES, no adverse events ≥5% were reported in participants following treatment with 300 mg PALFORZIA (n=265).^1
‡PALISADE was a randomized, double-blind, placebo-controlled safety and efficacy study conducted in the United States, Canada, and Europe evaluating PALFORZIA versus placebo in 496 participants aged 4 through 17 years with peanut allergy.^1,6
§RAMSES was a randomized, double-blind, placebo-controlled safety study conducted in the United States and Canada evaluating PALFORZIA versus placebo in 506 participants aged 4 through 17 years with peanut allergy.^1
¶Includes preferred terms of abdominal pain, abdominal pain upper, and abdominal discomfort.^1
#Includes preferred terms of oral pruritus, tongue pruritus, and lip pruritus.^1
∆The anaphylactic reaction preferred term includes systemic allergic reactions of any severity, or which severe anaphylaxis was reported in four PALFORZIA-treated participants (0.6%) during Up-Dosing and one PALFORZIA-treated participant (0.3%) during Maintenance dosing.¹

Anaphylactic reactions:

In PALFORZIA safety data, anaphylactic reaction includes systemic allergic reactions of any severity:¹

Severe anaphylaxis was reported in 0.6% of participants (4/709) during Up-Dosing and in 0.3% of participants (1/310) during Maintenance dosing across studies.¹

Percentage of patient-reported TEAEs and severity over time⁴

PALFORZIA safety continued to improve over time (Pooled safety analysis of patients aged 4–17 years from 6 PALFORZIA clinical trials)⁴

Adapted from: Bird JA, et al. 2023.⁴

From a pooled safety analysis from six PALFORZIA clinical trials and three open-label extension studies to describe additional long-term pooled safety data from baseline through approximately 5 years of treatment.⁴

In children and adolescents, continued daily treatment with PALFORZIA beyond 1 year has demonstrated an acceptable safety profile with continued and improved efficacy.⁵