Safety and efficacy of epicutaneous immunotherapy with DBV712 (peanut patch) in peanut allergy

Figures & data

Figure 1. Overview of mechanism of action with the peanut patch.

The peanut patch contains 250 µg of dried peanut protein on a film disc that is placed on top of a doubled-sided adhesive foam ring. When placed on the skin the film disc and foam ring, which are held in place by an adhesive overlay, form a condensation chamber. Natural water loss from the skin leads to solubilization of the peanut allergen which is taken up by antigen-presenting cells, such as Langerhans cells, in the superficial layers of the non-vascularized epidermis.

Table 1. Completed peanut patch phase 3 trials.

Study Name Study Duration [References]	Study Objective(s)	Study Population	Study Design	Dosage	Baseline Characteristics of Participants
PEPITES 2016–2017 [12,13]	Efficacy and Safety	Children aged 4–11 years (N = 356)	12-month RCT	Active treatment or placebo, daily	History of peanut allergy, SPT ≥ 6 mm for participants aged 4–5 years or SPT ≥ 8 mm for participants aged 6–11 years, sIgE > 0.7 kUA/L, ED ≤ 300 mg of peanut protein at entry DBPCFC, severe anaphylaxis excluded
PEOPLE (OLE to PEPITES) 2017–2023 [14]	Efficacy and Safety^a	Children aged 4–11 years at the time of enrollment in PEPITES (N = 198)	24- or 36-month^b open-label, active treatment followed by an additional 24-month open-label active treatment	Active treatment, daily	Included only eligible participants who completed PEPITES study
REALISE 2016–2020 [15]	Safety	Children aged 4–11 years (N = 393)	6-month RCT + OLE	Active treatment or placebo daily for the first 6 months followed by 30 to 36 months of active treatment, daily	History of peanut allergy, SPT ≥ 8 mm, sIgE ≥ 14 kUA/L
EPITOPE 2017– 2022 [16]	Efficacy and Safety	Toddlers aged 1–3 years (N = 362)	12-month RCT	Active treatment or placebo, daily	Documented or high suspicion of peanut allergy, sIgE > 0.7 kUA/L, SPT ≥ 6 mm, and ED ≤ 300 mg peanut protein at entry DBPCFC; severe anaphylaxis excluded

DBPCFC, double-blind, placebo-controlled food challenge; ED, eliciting dose; OLE, open-label extension; RCT, randomized controlled trial; sIgE, specific immunoglobulin E; SPT, skin prick test.

^aWith the exception of the results presented for “Other outcomes: Improvements in Food Allergy Quality of Life Questionnaire,” the results presented are restricted to the outcomes of those participants who were initially randomized to receive active treatment in PEPITES and who have received a further 2 years of active treatment in PEOPLE. It does not include those participants initially randomized to placebo.

^bParticipants in the active group in PEPITES received 24 months of open-label active treatment while participants initially in the placebo group received 36 months of open-label active treatment. Both arms had the option to continue for an additional 24 months of active treatment.

Figure 2. Proportion of treatment responders between active and placebo groups in children aged 1–3 years (a) and aged 4–11 years (b, c).

The primary measure of treatment effect compared the percentages of treatment responders between the active and placebo groups after 12 months of treatment among all randomized participants aged 1–3 years (a) and 4–11 years (b). Treatment responder defined as Month 12 ED ≥ 1000 mg (if baseline ED >10 mg) or ≥ 300 mg (if baseline ED ≤ 10 mg).

Proportion of participants aged 4–11 years meeting prespecified primary outcome at Months 12 and 36 in PEOPLE PP set according to primary outcome criteria in PEPITES. The PP set was defined as those participants who completed all treatment according to the study protocol without major deviations that could affect the assessment of the treatment effect, which included an evaluable DBPCFC performed as required by the protocol at Months 12 and 36 and compliance of ≥ 80% (c). CI, confidence interval; DBPCFC, double-blind, placebo-controlled food challenge; ED, eliciting dose; PP, per protocol.

Figure 3. Proportion of participants achieving an eliciting dose of ≥ 1000 mg at month 12 with the peanut patch.

A key efficacy endpoint measured the proportion of participants achieving an ED ≥ 1000 mg after 12 months of active treatment in children aged 1–3 years in EPITOPE (a) and 4–11 years in PEPITES (b). The change in the proportion of participants aged 4–11 years achieving an ED ≥ 1000 mg between Month 12 and Month 36 was assessed in the open-label extension PEOPLE study. CI, confidence interval; ED, eliciting dose.

Figure 4. Changes in reaction severity during DBPCFC between month 0 and month 12.

The severity of reactions during DBPCFC was graded by the investigator according to PRACTALL scoring as absent, mild, moderate, or severe in children aged 1–3 years in EPITOPE (a) and aged 4–11 years in PEPITES (b) [52].

Reaction definitions: Grade 0: negative; Grade 1: only erythema, or erythema + infiltration; Grade 2: erythema, few papules; Grade 3: erythema, many or spreading papules; Grade 4: erythema, vesicles.

DBPCFC, double-blind, placebo-controlled food challenge.

Figure 5. Changes in frequency and severity of Treatment-emergent Adverse Events Over Time in the PEOPLE (a) and REALISE (b) trials.

Treatment-relatedness and severity were determined by the investigator.

TEAE, treatment-emergent adverse event.

Table 2. Treatment-related adverse events in participants treated with the peanut patch: overview of the peanut patch safety profile in completed phase 3 studies.

	EPITOPE [16] (N = 244) n (%)	PEPITES [13,14] (N = 238) n (%)	PEOPLE [15] (N = 198) n (%)	REALISE [12] (N = 294) n (%)
Any TEAE related to the peanut patch^a	244 (100)	142 (59.7)	158 (79.8)	94 (32)
Serious TEAE related to the peanut patch	1 (0.4)	3 (1.3)	0 (0)	1 (0.3)
Severe TEAE related to the peanut patch	57 (23.4)	8 (3.4)	9 (4.5)	2 (0.7)
Anaphylaxis reaction related to the peanut patch	4 (1.6)	8 (3.4)	1 (0.5)	12 (4.1)
Participants treated with epinephrine (1 dose)	3	6	0	7
TEAEs leading to death	0	0	0	0
TEAE related to the peanut patch that led to permanent treatment discontinuation	7 (2.9)	4 (1.7)	2 (1)	4 (1.4)

TEAE, treatment-emergent adverse event.

^aDuring the first 6 months of PEPITES and REALISE only, the events of swelling, pruritus, and erythema were collected in the subject ediaries but not collected as an adverse event.

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