Safety Profile

Consistent safety profile across clinical studies

Adverse reactions were more frequently reported during Up-Dosing and decreased during Maintenance dosing.1

Study 1 (PALISADE) was a randomized, double-blind, placebo-controlled efficacy and safety study where 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 where 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 years1*

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

Organized by system organ class/preferred term.†

Study 1 & Study 2 Initial Dose Escalation

PALFORZIA

n=(709)

Placebo

n=(292)

Study 1 & Study 2 Up-Dosing

PALFORZIA

n=(693)

Placebo

n=(289)

Study 1 Maintenance DosingMaintenance Dose

PALFORZIA

n=(310)

Placebo

n=(118)

Gastrointestinal disorders

Abdominal pain‡

185 (26.1%)
24 (8.2%)
465 (67.1%)
100 (34.6%)
90 (29.0%)
20 (16.9%)

Vomiting

22 (3.1%)
15 (5.1%)
253 (36.5%)
47 (16.3%)
50 (16.1%)
14 (11.9%)

Nausea

60 (8.5%)
2 (0.7%)
224 (32.3%)
41 (14.2%)
45 (14.5%)
8 (6.8%)

Oral pruritus§

62 (8.7%)
9 (3.1%)
216 (31.2%)
30 (10.4%)
51 (16.5%)
7 (5.9%)

Oral paresthesia

13 (1.8%)
7 (2.4%)
94 (13.6%)
11 (3.8%)
23 (7.4%)
2 (1.7%)
Respiratory, thoracic, and mediastinal disorders

Throat irritation

66 (9.3%)
15 (5.1%)
279 (40.3%)
49 (17.0%)
43 (13.9%)
11 (9.3%)

Cough

18 (2.5%)
1 (0.3%)
221 (31.9%)
68 (23.5%)
61 (19.7%)
22 (18.6%)

Rhinorrhea

9 (1.3%)
4 (1.4%)
145 (20.9%)
50 (17.3%)
46 (14.8%)
9 (7.6%)

Sneezing

24 (3.4%)
8 (2.7%)
140 (20.2%)
31 (10.7%)
33 (10.6%)
5 (4.2%)

Throat tightness

18 (2.5%)
3 (1.0%)
98 (14.1%)
8 (2.8%)
20 (6.5%)
0 (0.0%)

Wheezing

4 (0.6%)
0 (0.0%)
85 (12.3%)
21 (7.3%)
19 (6.1%)
10 (8.5%)

Dyspnea

2 (0.3%)
1 (0.3%)
53 (7.6%)
5 (1.7%)
17 (5.5%)
1 (0.8%)
Skin and subcutaneous tissue disorders

Pruritus

56 (7.9%)
16 (5.5%)
225 (32.5%)
59 (20.4%)
45 (14.5%)
14 (11.9%)

Urticaria

28 (3.9%)
10 (3.4%)
197 (28.4%)
54 (18.7%)
63 (20.3%)
17 (14.4%)
Immune system disorders

Anaphylactic reaction

5 (0.7%)
1 (0.3%)
63 (9.1%)
10 (3.5%)
27 (8.7%)
2 (1.7%)
Ear and labyrinth disorders

Ear pruritus

5 (0.7%)
1 (0.3%)
41 (5.9%)
2 (0.7%)
7 (2.3%)
0 (0.0%)

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. *Treatment-emergent adverse reactions reported in ≥5% of participants treated with PALFORZIA and ≥5% percentage points greater than reported in participants treated with placebo in any dosing phase (aged 4 through 17 years).
  2. †Adverse events were coded to system organ class and preferred term using the MedDRA, version 19.1.
  3. In Study 2, no adverse events ≥5% were reported in participants following treatment with 300 mg PALFORZIA (N=265).
  4. ‡Includes preferred terms of abdominal pain, abdominal pain upper, and abdominal discomfort.
  5. §Includes preferred terms of oral pruritus, tongue pruritus, and lip pruritus.
  6. 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.

MedDRA = Medical Dictionary for Regulatory Activities.

Eosinophilic Gastrointestinal Disease

In clinical studies, 28 of 1050 (2.7%) participants were referred for a gastroenterology evaluation, and 17 of these 28 participants reported undergoing an esophagogastroduodenoscopy (EGD). Of participants who underwent an EGD, 12 were diagnosed with biopsy-confirmed eosinophilic esophagitis while receiving PALFORZIA compared with 0 of 292 (0%) participants receiving placebo. After discontinuation of PALFORZIA, symptomatic improvement was reported in 12 of 12 participants. In 8 participants with available follow-up biopsy results, eosinophilic esophagitis was resolved in 6 participants and improved in 2 participants.

References

  1. PALFORZIA [package insert]. Brisbane, CA: Aimmune Therapeutics, Inc.
  2. The PALISADE Group of Clinical Investigators: Vickery BP, Vereda A, Casale TB, et al. Supplementary Appendix. N Engl J Med. 2018;379(suppl):1991-2001.