Efficacy and Safety of Epicutaneous Immunotherapy (EPIT) for Peanut Allergy in Subjects With and Without Concomitant Food Allergies

Philippe Bégin, MD, PhD, FRCPC Director, Oral Immunotherapy ClinicCHU Sainte-Justine, Montreal, QC, Canada

Philippe Bégin, Gordon Sussman, Kirsten Beyer, Roxanne C. Oriel, Lara Ford, Wayne Shreffler, Dianne E. Campbell, Todd D. Green, Robin Mukherjee, David M. Fleischer

Disclosures

Type Company

Employment full time/part time None

Research grant (PI, collaborator, or consultant; pending and received grants) DBV Technologies, Sanofi, Regeneron, Novartis

Other research support None

Speakers bureau/honoraria Novartis, ALK, Aralez, DBV Technologies

Ownership interest (stock, stock-options, patent or intellectual property) None

Consultant/advisory board Novartis, ALK, Aralez, Pfizer, Sanofi-Genzyme

In relation to this presentation, I declare the following real or perceived conflicts of interest:

Background1

Study Objective2

Methods3

Results4

Table of Contents

Conclusions5

Background – The Burden of Peanut Allergy1

240-550million

individuals worldwide suffer from food allergy1

Among common food allergies, peanut allergy

patients report the highest rate of severe reactions2,3

1. World Allergy Organization. WAO White Book on Allergy: Update 2013. http://www.worldallergy.org/UserFiles/file/WhiteBook2-2013-v8.pdf. Accessed May 18, 2020. 2. Gupta RS, et al. Pediatrics. 2018;142:e20181235. 3. Gupta RS, et al. JAMA Netw Open. 2019 Jan 4;2:e185630. 4. Al-Muhsen S, et al. CMAJ. 2003;168:1279-1285. 5. Deschildre A, et al. Clin Exp Allergy. 2016;46:610-620. 6. Jones SM, Burks AW. N Engl J Med. 2017;377:1168-1176. 7. Green TD, et al. Pediatrics. 2007;120:1304-1310. 8. Cherkaoui S, et al. Clin Transl Allergy. 2015;5:16. 9. Neuman-Sunshine DL, et al. Ann Allergy Asthma Immunol. 2012;108:326-331.

In some patients, reactions can occur after exposure to low doses of peanut4,5

Even trace amounts of peanut can trigger a reaction, including

potentially severe reactions4,5

Standard of care for peanut allergy is strict avoidance plus personalized medical intervention plans…6

…however, despite practicing strict avoidance, accidental exposure often occurs and commonly leads to allergic reactions7-9

Avoidance is often characterized by a number of unmet needs, as patients and caregivers are often left to manage the condition by themselves

Background – Unmet Need in the Management of Peanut Allergy11

The goal of food allergy care should be the empowerment of patients and caregiversFigure from Bégin P, et al. 20201 (CC license http://creativecommons.org/licenses/by/4.0/).1. Bégin P, et al. Allergy Asthma Clin Immunol. 2020;16(20). https://doi.org/10.1186/s13223-020-0413-7.

Considerations for balanced decision-making in medicine

TECHNICAL CONSIDERATIONS

HUMAN CONSIDERATIONS

ETHICAL CONSIDERATIONS

DECISION

Background – Epicutaneous Immunotherapyfor the Management of Peanut Allergy1

Viaskin Peanut 250 µg (VP250)1,2

• Single, daily-dose patch o Applied to the back

• Dose: 250 µg o ~1/1000 of a peanut3

• 2-week at-home treatment initiation leading to 24-hour wear time

• No restrictions based on illness or daily activities required

1. Sampson HA, et al. JAMA. 2017;318:1798-1809. 2. Tilles SA, et al. Ann Allergy Asthma Immunol. 2018;121:145-149. 3. Parrish CP. Am J Manag Care. 2018;24:S419-S427.

Background – VP250 Clinical Trial Program1-71

1. Sampson HA, et al. JAMA. 2017;318:1798-1809. 2. Fleischer DM, et al. JAMA. 2019;321:946-955. 3. DBV Technologies. https://www.dbv-technologies.com/wp-content/uploads/2017/09/4221-pr-people-eng-pdf-1.pdf. Accessed May 18, 2020. 4. ClinicalTrials.Gov. NCT02916446. https://clinicaltrials.gov/ct2/show/NCT02916446. Accessed May 18, 2020. 5. ClinicalTrials.Gov. NCT03859700. https://clinicaltrials.gov/ct2/show/NCT03859700. Accessed May 18, 2020. 6. ClinicalTrials.Gov. NCT03211247. https://clinicaltrials.gov/ct2/show/NCT03211247. Accessed May 18, 2020.7. DBV. Press Release. https://www.dbv-technologies.com/wp-content/uploads/2018/10/pr-epitope-part-b-fpi-final_102618.pdf. Accessed May 18, 2020.

Phase 3 N=3934–11 years of age36 months (ongoing)

Phase 3 Part A: N=51; Part B: N=3501–3 years of age12 months (ongoing)

Phase 3 N=All eligible patients who complete EPITOPE1–3 years of age36 months (enrolling)

Open-label follow up to EPITOPE

Real Life Useand Safety

Phase 2bVIPES

OLFUS-VIPES

N=171 (OLFUS-VIPES)6–55 years of ageVIPES: 12 monthsOLFUS-VIPES: 24 months

Phase 3 N=3564–11 years of age12 months

Phase 3N=2984–11 years of age60 months (ongoing)Open-label follow-up

to PEPITES

Background – VP250 Clinical Trial Data: Phase 3 PEPITES1

*Participants with missing food challenge values at 12 months were counted as nonresponders in this analysis.AE=adverse event; CI=confidence interval; ITT=intent-to-treat; TEAE=treatment emergent adverse event.1. Fleischer DM, et al. JAMA. 2019;321(10):946-955. 2. Davis CM, et al. Poster presented at: AAAAI Annual Meeting 2019. February 22-25, 2019; San Francisco, CA. 3. Lange L, et al. Poster presented at: EAACI Congress 2019. June 1-5, 2019; Lisbon, Portugal.

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About a third of patients have more than one food allergy. This increases to 78% when considering food allergy referral practices1

Background – Patients With Multiple Food Allergies1

1. Park JH, et al. J Allergy Clin Immunol. 2010;125(2, Suppl1):AB216. 2. Christie L, et al. J Am Diet Assoc. 2002;102:1648-1651. 3. Sicherer SH, et al. Ann Allergy Asthma Immunol. 2001;87:461-464. 4. Wang J. Curr Allergy Asthma Rep. 2010;10:271-277. 5. Gupta RS, et al. Pediatrics. 2011;128:e9-17. 6. Bégin P, et al. Allergy Asthma Clin Immunol. 2020;16(20). https://doi.org/10.1186/s13223-020-0413-7.

Multi-food allergies are generally more severe, have greater impact on quality of life, and are less likely to spontaneously resolve2-5

There is a need for personalized care, considering the heterogeneity and specificity of the condition and individual patient contexts6

Study Objective2

• To examine efficacy and safety of VP250 in peanut-allergic children to understand whether concomitant food allergies (CFA) affect the treatment response or safety outcomes

Methods – Study Design3

• Primary outcome: response rate difference between VP250 and placebo treatment groups after 12 months* • Post-hoc analysis of the differences in efficacy and safety among peanut-allergic children with and without CFA at

study entry • Response rate for each group calculated using Wilson 95% CI and difference between VP250 and placebo response

calculated with Newcombe two-sided 95% CI. Participants with missing food challenge values at 12 months were counted as nonresponders in this analysis

*Treatment response was defined as a post-treatment ED of ≥300 mg or ≥1000 mg of peanut protein for subjects with an initial ED of ≤10 mg or >10 mg, respectively.CFA=concomitant food allergies; CI=confidence interval; DBPCFC=double-blind, placebo-controlled food challenge; M=month.1. Fleischer DM, et al. JAMA. 2019;321:946-955.

Phase 3, randomized, double-blind, placebo-controlled trial of VP250 in children 4–11 years of age (N=356)1

Placebo

VP250

n=118

n=238

PEPITES

M0 M12Denotes a DBPCFC.

Results – Patient Distribution4

*Twenty-eight of the 150 children had a history of a food allergy other than peanut which had resolved by baseline, and they were no longer allergic to foods other than peanut at time of study entry.

Children aged 4–11 years with peanut allergy

(N=356)

Children with concomitant food allergies (CFA)

(n=206)

Children with peanut allergy only (PAO)

(n=150)*

VP250(n=141)

Placebo(n=65)

VP250(n=97)

Placebo(n=53)

Results – Baseline Characteristics4

CFA (n=206) PAO (n=150)

Age (years), mean (SD) 7.4 (2.2) 7.3 (2.2) Sex, n (%)

Male 137 (67) 81 (54)Race, n (%)

CaucasianAsianOther

159 (77)19 (9)

28 (14)

131 (87)8 (5)

11 (7)ED ≤10 mg at baseline, n (%) 39 (19) 22 (15)Median PN-IgE, kU/L (IQR) 101 (23–249) 68 (22–150)Median PN-IgG4 (IQR) 0.8 (0.39–1.69) 0.5 (0.23–1.13)Median PN-SPT, mm (IQR) 11 (9–14) 11 (9–14)

CFA=concomitant food allergies; ED=eliciting dose; IQR=interquartile range; PAO=peanut allergy only; PN=peanut; SD=standard deviation; SPT=skin prick test.

Results – Efficacy 4

AD=atopic dermatitis; CFA=concomitant food allergies; CI=confidence interval; PAO=peanut allergy only.

Improvement in the predefined primary outcome was consistently in favor of VP250irrespective of whether children had CFA or PAO at study entry

Subgroup (ongoing history)

VP250 response rate

% (n/N)

Placebo response rate

% (n/N)

Difference (95% CI)

P value for interaction

Asthma (N=159)

No asthma (N=197)

36.9 (41/111)

33.9 (43/127)

12.5 (6/48)

14.3 (10/70)

24.4% (9.6–35.8)

19.6% (6.9–30.3)0.640

Eczema/AD (N=163)

No eczema/AD (N=193)

43.6 (44/101)

29.2 (40/137)

17.7 (11/62)

8.9 (5/56)

25.8% (11.2–38.1)

20.3% (7.8–29.8)0.800

CFA (N=206)

PAO (N=150)

33.3 (47/141)

38.1 (37/97)

16.9 (11/65)

9.4 (5/53)

16.4% (3.3–27.3)

28.7% (14.6–40.0)0.167

-10 0 10 20 30 40 50

Favors Placebo Favors Treatment

Difference (95% CI)

Results – Safety 4

AESI=adverse events of special interest; CFA=concomitant food allergies; PAO=peanut allergy only; TEAE=treatment-emergent adverse event.

Very similar rates of TEAEs, as well as similar and low rates of TEAEs leading to permanent discontinuation, were observed between CFA and PAO groups

CFA PAOVP250 (n=141) Placebo (n=65) VP250 (n=97) Placebo (n=53)

TEAEs (n, %) 135 (95.7) 60 (92.3) 92 (94.8) 45 (84.9) Mild TEAEs 130 (92.2) 57 (87.7) 90 (92.8) 40 (75.5) Moderate TEAEs 80 (56.7) 27 (41.5) 46 (47.4) 25 (47.2) Severe TEAEs 10 (7.1) 0 4 (4.1) 2 (3.8) Serious TEAEs 3 (2.1) 3 (4.6) 4 (4.1) 2 (3.8)

TEAEs considered related to treatment 85 (60.3) 24 (36.9) 57 (58.8) 17 (32.1) Serious TEAEs considered related to treatment 1 (0.7) 0 2 (2.1) 0

TEAEs leading to permanent treatment discontinuation 2 (1.4) 0 2 (2.1) 0

TEAEs leading to temporary treatment discontinuation 22 (15.6) 6 (9.2) 10 (10.3) 5 (9.4)

Treatment-induced local TEAEs 82 (58.2) 17 (26.2) 55 (56.7) 16 (30.2) Systemic AESI 8 (5.7) 4 (6.2) 5 (5.2) 2 (3.8) Anaphylactic reaction related to treatment (investigator-assessed) 4 (2.8) 1 (1.5) 4 (4.1) 0

Conclusions5

• Over half of participants recruited in the PEPITES trial had CFA, suggesting that peanut EPIT addresses an unmet need in the multi-food allergic population

• In peanut-allergic children aged 4–11 years who were treated with EPIT for peanut allergy, improvement in the predefined primary outcome measured over the 12-month treatment period was in favor of VP250 over placebo, irrespective of whether they were allergic only to peanut or had CFA at study entry

• The safety and tolerability profiles were similar in peanut-allergic children randomized to VP250 with peanut allergy alone and peanut allergy with CFA

• These results are in line with those previously reported that found neither baseline asthma nor AD influenced the efficacy or safety of VP250

AD=atopic dermatitis; CFA=concomitant food allergies; EPIT=epicutaneous immunotherapy.

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