Objective COVID-19 in tralokinumab-treated patients with moderate-to-severe atopic dermatitis: case series from the ECZTEND long-term extension trial Andrew Blauvelt1, Andrew Pink2, Margitta Worm3, Richard Langley4, Antonio Costanzo5, Le Gjerum6, Emilie Jorgensen6, Joshua Corriveau7, Emma Guttman-Yassky8 • There is special interest in the impact of COVID-19 on individuals with chronic immune-mediated diseases such as atopic dermatitis (AD), including concerns that patients treated with immunomodulatory therapies for these diseases may have increased risk of developing COVID-19 or more severe disease with worse outcomes following infection with SARS-CoV-2 • AD is a chronic inflammatory disease,1 characterized by eczematous skin lesions and multiple symptoms, including pruritus, sleep disturbance, and depression2-4 • Tralokinumab is a high-affinity, fully human, monoclonal antibody designed to specifically neutralize interleukin-13, a key driver of the underlying inflammation in AD5-7 • Phase 3 trials have established the efficacy and safety of tralokinumab for up to 52 weeks in adult patients with moderate-to-severe AD8,9 • An ongoing, open-label extension trial, ECZTEND (NCT03587805), is investigating the long-term safety and efficacy of tralokinumab in patients with AD who participated in previous tralokinumab trials To describe the outcomes of adult patients diagnosed with COVID-19 while participating in the tralokinumab long term extension trial, ECZTEND. 1Oregon Medical Research Center, Portland, OR, USA; 2St. John's Institute of Dermatology, Guy’s and St. Thomas’ Hospitals, London, UK; 3Division of Allergy and Immunology, Department of Dermatology, Venereology and Allergy, Charité –Universitätsmedizin Berlin, Berlin, Germany; 4Division of Clinical Dermatology and Cutaneous Science, Dalhousie University, Halifax, NS, Canada; 5Dermatology Unit Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini, 20089, Pieve Emanuele, Milano, Italy. Skin Pathology Laboratory, Humanitas Research Hospital IRCCS, Via Manzoni 56, 20089, Rozzano, Milano, Italy; 6LEO Pharma A/S, Ballerup, Denmark; 7LEO Pharma Inc., Madison, NJ, USA; 8Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA Introduction Methods • As shown in Figure 1, ECZTEND is an ongoing, 5 year, open-label, single-arm, multicenter, long-term extension trial in patients with AD who participated in parent tralokinumab trials (ECZTRA 1-8 and TraSki)a o Approximately 1600 patients with moderate-to-severe AD across Canada, the United States, Europe, and Japan are participating in ECZTEND o Patients received subcutaneous tralokinumab 300 mg Q2W plus optional TCS after a 300 mg or 600 mg loading dose of tralokinumab o Safety follow-up 16 weeks after last investigational medicinal product • Key inclusion criteria for ECZTEND: o Completed treatment period(s) in a tralokinumab parent trial (ECZTRA 1-8 or TraSki) without any safety concerns o Complied with the clinical trial protocol in the parent trial o Able and willing to self-administer tralokinumab, or have it administered by a caregiver, at home after the initial 3 injection visits at trial site o Applied a stable dose of emollient (minimum twice daily) for at least 14 days before baseline • Here, we report a case series of 51 adult patients with moderate-to-severe AD who had confirmed cases of COVID-19 during treatment with tralokinumab every 2 weeks o Patients were not required to discontinue tralokinumab treatment following a COVID-19 diagnosis, if continuation was deemed appropriate by the investigator o This is an interim analysis of data collected through February 26, 2021 Figure 1. ECZTEND open-label extension trial design. Table 1. Baseline demographics for patients in ECZTEND with confirmed cases of COVID-19. Patient characteristics References Disclosures Concluding Remarks In the present study, COVID-19 cases were predominately mild or moderate (96%), and all patients continued tralokinumab treatment following COVID-19 diagnosis. • Severe COVID-19 is characterized by release of pro-inflammatory cytokines, leading to pulmonary inflammation and impairment of lung function • IL-13 is not thought to be a major contributor to host defense mechanisms against viral infections • The recent ECZTRA 5 vaccine study showed that non-live vaccines could be safely administered and can elicit normal immune responses in patients treated with tralokinumab10 1. Weidinger S, Novak N. Lancet. 2016;387:1109–22; 2. Eckert L, et al. J Am Acad Dermatol. 2017;77:274–9.e273; 3. Silverberg JI, et al. Ann Allergy Asthma Immunol. 2018;121:340–7; 4. Dalgard FJ, et al. J Invest Dermatol. 2015;135:984–91; 5. Bieber T. Allergy. 2020;75:54–62; 6. Tsoi LC, et al. J Invest Dermatol. 2019;139:1480–9; 7. Popovic B, et al. J Mol Biol. 2017;429:208–19; 8. Wollenberg A, et al. Br J Dermatol. 2020. doi:10.1111/bjd.19574; 9. Silverberg JI, et al. Br J Dermatol. 2020. doi:10.1111/bjd.19573; 10. Merola J, et al. Tralokinumab does not impact vaccine-induced immune responses: results from a 30-week, randomized, placebo-controlled trial in adults with moderate- to-severe atopic dermatitis. J Am Acad Dermatol. 2021. Published online 17 March 2021. Doi: 10.1016/j.jaad.2021.03.032 • Andrew Blauvelt is a scientific adviser and clinical study investigator for AbbVie, Aclaris, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dermira, Eli Lilly, FLX Bio, Forte, Galderma, Janssen, LEO Pharma, Novartis, Ortho Derm, Pfizer, Regeneron Pharmaceuticals, Inc., Sandoz, Sanofi Genzyme, Sun Pharma, UCB Pharma, and a paid speaker for AbbVie • Andrew Pink reports personal fees and nonfinancial support from LEO Pharma, Novartis, and UCB; and personal fees from AbbVie, Almirall, Janssen, La Roche Posay Lilly, and Sanofi • Margitta Worm declares that she has receipt honoraria or consultation fees by ALK-Abelló Arzneimittel GmbH, Mylan Germany GmbH, LEO Pharma GmbH, Sanofi-Aventis Deutschland GmbH, Regeneron Pharmaceuticals, Inc., DBV Technologies S.A, Stallergenes GmbH, HAL Allergie GmbH, Allergopharma GmbH & Co. KG, Bencard Allergie GmbH, Aimmune Therapeutics UK Limited, Actelion Pharmaceuticals Deutschland GmbH, Novartis AG and Biotest AG • Richard Langley has served and has received compensation in the form of grant funding and/or honoraria as principal investigator for and is on the scientific advisory board or has served as a speaker for AbbVie , Amgen , Boehringer Ingelheim , Celgene , Janssen , LEO Pharma , Eli Lilly , Merck , Novartis , Pfizer , Sun Pharma , and UCB • Antonio Costanzo has served on advisory boards Celgene, UCB, Eli Lilly, Pfizer, Janssen, Novartis, Sanofi-Genzyme and MSD • Le Gjerum, Emilie Jorgensen, and Joshua Corriveau are employees of LEO Pharma A/S • Emma Guttman-Yassky has received honoraria for consultant services from AbbVie, Almirall, Amgen, Asana Biosciences, Boerhinger Ingelhiem, Cara Therapeutics, Celgene, Concert, DBV, Dermira, DS Biopharma, Lilly, EMD Serono, Escalier, Galderma, Glenmark, Kyowa Kirin, LEO Pharma, Mitsubishi Tanabe, Pfizer, RAPT Therapeutics, Regeneron, Sanofi, Sienna Biopharma, and Union Therapeutics and received research grants for investigator services from AbbVie, Almirall, Amgen, AnaptysBio, Asana Biosciences, Boerhinger Ingelhiem, Celgene, Concert, Dermavant, Dermira, DS Biopharma, Lilly, Glenmark, Galderma, Innovaderm, Janssen, Kiniska, Kyowa Kirin, LEO Pharma, Novan, Pfizer, Ralexar, Regeneron, Sienna Biopharma, UCB, and Union Therapeutics Acknowledgements • The ECZTEND clinical trial was sponsored by LEO Pharma • Editorial support was provided by Clair Geary, PhD of Alphabet Health (New York, NY), supported by LEO Pharma, according to Good Publication Practice guidelines (https://www.ismpp.org/gpp3) Table 3. Adverse events details for patients in ECZTEND with confirmed cases of COVID-19. Originally presented at Revolutionizing Atopic Dermatitis (RAD), June 13, 2021. Results COVID-19 Case Series (N=51) Age Mean (range) 37.7 (19-70) Sex Male, n (%) 22 (43%) Female, n (%) 29 (57%) Baseline BMI Mean (range) 27.6 (16.3-50.8) Geographic region North America, n (%) 15 (29%) Europe, n (%) 36 (71%) Table 2. Clinical characteristics for patients in ECZTEND with confirmed cases of COVID-19. • COVID-19 severity was predominantly mild (35/51, 68.6%) or moderate (14/51, 27.5%), and all patients with mild or moderate disease recovered fully (Table 3) • The two patients who experienced severe cases (2/51, 3.9%) had multiple risk factors and comorbidities, including obesity, COPD, and cardiovascular disease. Both were hospitalized and subsequently recovered (one with sequelae); neither case was reported as related to tralokinumab treatment • Mean duration of infection was 15 days (range 1-39 days) • Only two of the 51 COVID-19 cases were reported as possibly related to tralokinumab treatment; both were mild or moderate cases occurring in patients under the age of 30 • All (51/51) patients continued tralokinumab treatment, the majority (38/51, 75%) without dose interruptions following COVID-19 diagnosis • Regarding comorbidities that confer additional risk of severe COVID-19, 59% (n/N, 30/51) of patients had asthma and 10% (5/51) had hypertension; cardiovascular disease was present in 2 patients and chronic obstructive pulmonary disease (COPD) and diabetes mellitus were present in 1 patient each (Table 2) • In the ECZTEND study, 19 patients have received the first dose of COVID-19 vaccine and 6 patients have received the second dose; no patients had adverse events leading to permanent discontinuation after receiving the vaccine as per data cut-off Site visit. IGA, EASI, SCORAD, worst weekly pruritus NRS, eczema- related sleep NRS, use of topical treatment Screening and follow-up visits Home use training POEM, DLQI / CDLQI, EQ-5D-5Lc Antidrug antibody / pharmacokinetic measurement Weeks from first treatment in ECZTEND 5640322416 484 8–2 0 Screening period TCS use allowed Visit schedule until end of May 2021b 248 • Twenty-two male and 29 female patients were diagnosed with COVID-19 through February 2021 (Table 1) • The mean age was 37.7 years (range 19-70 years) and the mean BMI was 27.6 (range 16.3-50.8) COVID-19 Case Series (N=51) PYE tralokinumab (parent trial + ECZTEND) Mean 2.3 History of: Diabetes mellitus, n (%) 1 (2%) Cardiovascular disease, n (%) 2 (4%) Hypertension, n (%) 5 (10%) COPD, n (%) 1 (2%) Asthma, n (%) 30 (59%) COVID-19 Case Series (N=51) Disease duration in days Mean (range) 15.2 (1-39) Disease course Mild, n (%) 35 (69%) Moderate, n (%) 14 (27%) Severe, n (%) 2 (4%) Hospitalizations n (%) 2 (4%) Mean duration of stay (range) 7 (5-9) Possibly related to treatment n (%) 2 (4%) Recovery Full, n (%) 50 (98%) With sequelae, n (%) 1 (2%) Not recovered, n (%) 0 Tralokinumab continuation No dose interruption, n (%) 38 (75%) Dose interruption, n (%) 13 (25%) aPrevious treatment regimens in parent trials included tralokinumab q2w, q4w, or placebo +/- TCS bAfter May 2021, some site visits will be switched to telephone visits. bPatients from the parent trial ECZTRA 6 will not perform the EQ- 5D-5L. CDLQI, Children’s Dermatology Life Quality Index; DLQI, Dermatology Life Quality Index; EASI, Eczema Area and Severity Index; EQ- 5D-5L, EuroQol 5 Dimension Health Questionnaire 5-Level; IGA, Investigator’s Global Assessment; NRS, Numeric Rating Scale; POEM, Patient-Oriented Eczema Measure; q2w, every 2 weeks; SCORAD, SCOring Atopic Dermatitis; TCS, topical corticosteroid.