- |||||||||| Review, Journal: New and Emerging Systemic Treatments for Atopic Dermatitis. (Pubmed Central) - May 4, 2021
We review the published phase II and III data for dupilumab, tralokinumab, lebrikizumab, nemolizumab, anti-OX40 antibody, baricitinib, abrocitinib, and upadacitinib. The introduction of new agents may offer new options, but it remains to be seen how narrow-acting agents, like single interleukin inhibitors, will compare in safety and efficacy to broad-acting agents such as JAK inhibitors.
- |||||||||| Eucrisa (crisaborole) / Pfizer
[VIRTUAL] Treating Atopic Dermatitis in Kids: Symposium for Inflammatory Skin Disease 2021® Highlights () - Apr 29, 2021 - Abstract #DERFISDS2021DERF_ISDS_33;
Emerging systemic agents for AD include IL-13 inhibitors (tralokinumab and lebrikizumab), IL-31 inhibitor nemolizumab, and JAK inhibitors (abrocitinib, upadacitinib, baricitinib). These emerging treatments and approvals have the potential to drastically improve treatment of AD in children and thereby disease burden as well.
- |||||||||| Adtralza (tralokinumab) / LEO Pharma, AstraZeneca, lebrikizumab (LY3650150) / Roche, Almirall, Eli Lilly, Dupixent (dupilumab) / Sanofi, Regeneron
Review, Journal: Selective IL-13 inhibitors for the treatment of atopic dermatitis. (Pubmed Central) - Apr 24, 2021
The evidence supports the hypothesis that selective antagonism of IL-13 is sufficient to control AD, providing an improvement in the patient's quality of life. Therefore, the development of lebrikizumab and tralokinumab represents a new and exciting phase in the management of AD.
- |||||||||| A COMPUTATIONAL MODEL TO INVESTIGATE DRUG TARGETS IN AD PATIENTS WITH HETEROGENOUS RESPONSE TO BIOLOGIC DRUGS () - Apr 23, 2021 - Abstract #ISAD2021ISAD_148;
The mathematical model will serve as a computational platform for model-informed drug development for precision medicine, as it allows us to evaluate the validity of potential drug targets, including combinations of multiple targets, in stratified patients as well as the influence of pathophysiological backgrounds of patients on variability in drug response. Similar mathematical models can be developed for other diseases and drugs by conducting model-based meta-analysis on reported clinical efficacies of multiple drugs.
- |||||||||| THREE LEARNINGS FROM A PERFORMANCE REVIEW OF CLINICAL TRIALS IN ATOPIC DERMATITIS () - Apr 23, 2021 - Abstract #ISAD2021ISAD_59;
For biologics : dupilumab (IL4/ IL13), lebrikizumab (IL-13), tralokinumab (IL-13), and nemolizumab (IL-31)...An though it shouldn’t be a surprise, even biologics can have “off target” effects. The greatest learning: our patients will at last have a number of therapeutic options.
- |||||||||| Adtralza (tralokinumab) / LEO Pharma, AstraZeneca, Dupixent (dupilumab) / Sanofi, Regeneron
[VIRTUAL] Population Health Benefit of Introducing New Biologic Treatments in Atopic Dermatitis () - Apr 12, 2021 - Abstract #ISPOR2021ISPOR_90;
Moreover, three or more treatment options will further increase the number of treatment years. Therefore, it is important to have more biologic treatment options for patients with moderate-to-severe atopic dermatitis to reduce the number of untreated patient years.
- |||||||||| [VIRTUAL] EDU-F5: Emerging Therapies in Atopic Dermatitis: Managed Care Perspectives and Opportunities () - Apr 11, 2021 - Abstract #AMCP2021AMCP_10;
Due to the broad range of severity of atopic dermatitis, limited long-term data for newer AD agents, and affordability concerns the impact of formulary management strategies for AD medications will likely be significant.Learning Objectives: At the completion of this activity, participants should be able to:Describe the burden of disease for patients with atopic dermatitis. Describe the role of new and emerging therapies for patients with atopic dermatitis.Identify atopic dermatitis treatment recommendations based on the latest guidelines.Discuss the impact of formulary management strategies for atopic dermatitis medications.
- |||||||||| Adtralza (tralokinumab) / LEO Pharma, AstraZeneca
[VIRTUAL] Effects on type 2 immunity when specifically targeting the interleukin-13 cytokine with tralokinumab () - Apr 10, 2021 - Abstract #AADVMX2021AAD_VMX_855;
The serum concentrations of total immunoglobulin E (IgE) also showed a significant reduction at week 16 versus baseline. The reduced levels of CCL17 and IgE support the hypothesis that neutralization of the IL-13 cytokine alone may suffice to prevent Th2 signaling, allowing for modulation of type 2 immunity, including a decrease in IgE, without the need for direct blocking of the IL-4 pathway.
- |||||||||| Adtralza (tralokinumab) / LEO Pharma, AstraZeneca
[VIRTUAL] Long-term efficacy, safety, and adherence to tralokinumab treatment in moderate-to-severe atopic dermatitis for up to 3 years: interim readout of ECZTEND, a Phase 3, long-term extension trial () - Apr 10, 2021 - Abstract #AADVMX2021AAD_VMX_833;
P3
To date, 1025 patients have registered in ECZTEND, some for up to 3 years, with 711 patients previously assigned to tralokinumab q2w or q4w with or without optional topical corticosteroids in a parent trial. Interim ECZTEND results, based on the most recently available data in 2020, will be presented.
- |||||||||| [VIRTUAL] Comparative Efficacy and Safety of Systemic Therapies Used in Adult and Adolescent Moderate-to-Severe Atopic Dermatitis (AD): A Systematic Literature Review (SLR) and Network Meta-Analysis (NMA) () - Apr 10, 2021 - Abstract #AADVMX2021AAD_VMX_130;
Overall, 19 published RCTs (phase 2 and 3) of abrocitinib, baricitinib, dupilumab, lebrikizumab, nemolizumab, tralokinumab, and upadacitinib were included. Upadacitinib, abrocitinib, and dupilumab were the most effective systemic therapies, with similar incidence of AEs in short-term RCTs.
- |||||||||| Xolair (omalizumab) / Roche, Novartis
Review, Journal: Biological Therapies of Severe Asthma and Their Possible Effects on Airway Remodeling. (Pubmed Central) - Apr 7, 2021
Still, data on effects of particular biological therapies on AR in severe asthma are incomplete and require further studies. According to the American Thoracic Society research recommendations, future research shall focus on AR in asthma and improve drugs targeting AR, including the available and future monoclonal antibodies.
- |||||||||| Eucrisa (crisaborole) / Pfizer
OVERVIEW OF NEW THERAPIES IN AD () - Mar 31, 2021 - Abstract #ISAD2021ISAD_40;
Licensed systemic antihistamines (H1R-blockers) only have limited effects on AD related itch and eczema lesions, whereas only little data on the novel H4R-blockers is available. Combining the new therapies with existing adjuvant therapy including UV irradiation and topical anti-inflammatory treatment, as well as therapeutic patient education is an essential aspect of the art of dermatology.
- |||||||||| Adbry (tralokinumab-ldrm) / LEO Pharma, AstraZeneca
Enrollment closed, Combination therapy: ECZTRA 8: Tralokinumab in Combination With Topical Corticosteroids in Japanese Subjects With Moderate-to-severe Atopic Dermatitis (clinicaltrials.gov) - Mar 26, 2021
P3, N=126, Active, not recruiting,
We should proceed optimistically, yet cautiously, with the study of biologics in children. Recruiting --> Active, not recruiting
- |||||||||| Journal: Novel Therapeutic Approaches and Targets for Treatment of Atopic Dermatitis. (Pubmed Central) - Feb 9, 2021
The extreme clinical heterogeneity and the chronic progression of Atopic Dermatitis need for newer, safer and more effective treatments, able to control the disease and to improve the quality of life of affected patients. Dupilumab, and the other monoclonal antibodies and small molecules currently under investigation aim to improve the clinical management of Atopic Dermatitis.
- |||||||||| tralokinumab (CAT 354) / LEO Pharma, AstraZeneca
[VIRTUAL] Safety of specifically targeting interleukin-13 with tralokinumab in adult patients with moderate-to-severe atopic dermatitis: pooled analysis of five randomized, double-blind, placebo-controlled Phase 3 and Phase 2 trials () - Jan 5, 2021 - Abstract #RAD2020RAD_116;
P2, P2b, P
Dupilumab, and the other monoclonal antibodies and small molecules currently under investigation aim to improve the clinical management of Atopic Dermatitis. Introduction Atopic dermatitis (AD) is a chronic, debilitating, inflammatory skin disease1,2 characterised by eczematous lesions and multiple symptoms, including pruritus, sleep disturbance and depression.3-5 The type 2 cytokine interleukin 13 (IL-13) is a key driver of the underlying inflammation of AD and is overexpressed in lesional and non-lesional AD skin6,7 Tralokinumab is a fully human immunoglobulin G4 monoclonal antibody that specifically binds to the IL-13 cytokine with high affinity, preventing interaction with the IL-13 receptor and subsequent downstream IL-13 signalling, thus preventing its pro-inflammatory activity6-8 Tralokinumab 300 mg every 2 weeks (q2w), as monotherapy and in combination with topical corticosteroids (TCS), was efficacious in the treatment of patients with moderate-to-severe AD in three pivotal Phase 3 ECZTRA trials (ECZTRA 1 [NCT03131648], ECZTRA 2 [NCT03160885] and ECZTRA 3 [NCT03363854]), a Phase 2 trial (ECZTRA 5 [NCT03562377]) and a Phase 2b trial (NCT02347176)9 It is important to understand the safety profile of therapeutics used for the long-term treatment of patients with AD — A good safety profile is an important attribute for patients when selecting a treatment for AD10 objective To provide an overview of the pooled safety data from three Phase 3 ECZTRA trials and two Phase 2 trials to evaluate the safety of tralokinumab 300 mg q2w in adult patients with moderate-to-severe AD
- |||||||||| tralokinumab (CAT 354) / LEO Pharma, AstraZeneca
[VIRTUAL] Early changes in patient-relevant endpoints in three tralokinumab pivotal Phase 3 trials (ECZTRA 1-3) in adult patients with moderate-to-severe atopic dermatitis () - Jan 5, 2021 - Abstract #RAD2020RAD_115;
P3
Introduction Atopic dermatitis (AD) is a chronic, debilitating, inflammatory skin disease1,2 characterised by eczematous lesions and multiple symptoms, including pruritus, sleep disturbance and depression.3-5 The type 2 cytokine interleukin 13 (IL-13) is a key driver of the underlying inflammation of AD and is overexpressed in lesional and non-lesional AD skin6,7 Tralokinumab is a fully human immunoglobulin G4 monoclonal antibody that specifically binds to the IL-13 cytokine with high affinity, preventing interaction with the IL-13 receptor and subsequent downstream IL-13 signalling, thus preventing its pro-inflammatory activity6-8 Tralokinumab 300 mg every 2 weeks (q2w), as monotherapy and in combination with topical corticosteroids (TCS), was efficacious in the treatment of patients with moderate-to-severe AD in three pivotal Phase 3 ECZTRA trials (ECZTRA 1 [NCT03131648], ECZTRA 2 [NCT03160885] and ECZTRA 3 [NCT03363854]), a Phase 2 trial (ECZTRA 5 [NCT03562377]) and a Phase 2b trial (NCT02347176)9 It is important to understand the safety profile of therapeutics used for the long-term treatment of patients with AD — A good safety profile is an important attribute for patients when selecting a treatment for AD10 objective To provide an overview of the pooled safety data from three Phase 3 ECZTRA trials and two Phase 2 trials to evaluate the safety of tralokinumab 300 mg q2w in adult patients with moderate-to-severe AD Introduction Atopic dermatitis (AD) is a chronic, inflammatory skin disease, with an estimated prevalence of between 2.1% and 4.9% in adults across North America, Europe, and Japan1 Moderate-to-severe AD is characterized by symptoms including excessive dryness, scaling, red or inflamed skin, blisters or bumps, open sores or oozing, and intense itching.2 These symptoms can be severely debilitating to patients and their quality of life, resulting in sleep disturbance, pain, and depression2 The pathogenesis of AD is complex and multifactorial, combining skin barrier dysfunction and immune dysregulation, leading to chronic type 2 inflammation3,4 Interleukin (IL)-13, a key type 2 cytokine, has been identified as a key driver of the underlying inflammation of AD, with IL-13 levels within lesional skin correlating with AD severity5-8 Tralokinumab is a fully human monoclonal antibody which specifically neutralizes IL-139 - Recent Phase 3, placebo-controlled trials have investigated tralokinumab in the treatment of moderate-to- severe AD as a monotherapy (ECZTRA 1, NCT03131648; ECZTRA 2, NCT03160885) and in combination with topical corticosteroids (TCS) [ECZTRA 3, NCT03363854] - Efficacy results from these trials were promising, with significantly more patients achieving the primary endpoints of Investigator’s Global Assessment (IGA) score of 0 or 1 and Eczema Area and Severity Index (EASI) score of 75 (a 75% reduction in EASI score) at 16 weeks with tralokinumab versus placebo in all three studies It is important to assess the efficacy of tralokinumab in terms of patient-reported outcomes (PROs), which are vital for providing insight on the real-life value of treatments for AD Objective The objective of this analysis was to examine early changes in several PRO measures across the ECZTRA 1/2 and ECZTRA 3 trials
- |||||||||| Clinical, Journal: Efficacy of biologics in atopic dermatitis. (Pubmed Central) - Dec 23, 2020
Recent advancements in understanding AD pathogenesis resulted in the exponential expansion of its therapeutic pipeline, particularly following the success and FDA-approval of dupilumab...Nevertheless, this biologic does not work for everyone, highlighting the need for a more precise approach to address the unique immune fingerprints of each AD subset. Ultimately targeted therapeutics will complement our understanding of the AD molecular map and help push AD management into an era of personalized medicine.
- |||||||||| Adbry (tralokinumab-ldrm) / LEO Pharma, AstraZeneca
Enrollment change, Trial completion date, Trial primary completion date: Long-term Extension Trial in Subjects With Atopic Dermatitis Who Participated in Previous Tralokinumab Trials - ECZTEND (clinicaltrials.gov) - Dec 22, 2020
P3, N=1600, Enrolling by invitation,
Ultimately targeted therapeutics will complement our understanding of the AD molecular map and help push AD management into an era of personalized medicine. N=1125 --> 1600 | Trial completion date: Sep 2021 --> Jun 2024 | Trial primary completion date: Jun 2021 --> Jun 2024
- |||||||||| [VIRTUAL] What You Need to Know About Atopic Dermatitis () - Nov 26, 2020 - Abstract #FCPANP2020FCPANP_64;
First-in-class tapinarof, an aryl hydrocarbon receptor modulating agent, has also been shown to be effective in improving skin barrier function, modulating immune function, and reducing oxidative stress...Dupilumab, the IL-4 and IL-13 blocker, recently received FDA-approval for use in children as young as age 6...Enter tralokinumab, a selective IL-13 blocker...Golant noted that oral formulations are being developed for moderate to severe atopic dermatitis and, in phase III trials, have been demonstrated to ameliorate disease severity and decrease pruritis. The therapeutic floodgates have been opened for atopic dermatitis with seemingly boundless possibilities.
- |||||||||| Humira (adalimumab) / Eisai, AbbVie, Differin (adapalene) / Galderma, Cimzia (certolizumab pegol) / Astellas, UCB, Eli Lilly
[VIRTUAL] Therapeutic Update () - Nov 26, 2020 - Abstract #FCPANP2020FCPANP_61;
Similar concepts have allowed combination of halobetasol .01% and tazarotene .045%, calcipotriene as a foam and halobetasol as a lotion...Goldenberg also highlighted new topicals including tapinarof and a topical PDE-4 inhibitor, roflumilast...Goldenberg then summarized updates on biologics for the management of psoriasis including: the improved hemoglobin A1c and weight control in diabetic patients with psoriasis on Otezla (PDE-4 inhibitor); long-term safety of tumor necrosis factor biologics adalimumab and certolizumab pegol as well as the ability for patients to self-administer certolizumab at home; the enduring efficacy of IL-17 blockers including congruent patient-reported data for ixekizumab, sustained long-term response data for secukinumab to 52 weeks and for brodalumab to 60 weeks; data demonstrating that although IL-17 blockers (specifically secukinumab) may work faster, guselkumab had a higher proportion of patients reach PASI 90/100 by week 48 and that rizankizumab outperformed adalimumab in moderate to severe plaque psoriasis management; and finally promising results for tyrosine kinase 2 inhibitors improving quality of life in psoriasis patients...Goldenberg closed with a brief discussion of advancements in management of viral dermatoses (single-use cantharidin for molluscum, buccal-adhesive acyclovir tablets), personal care moisturizers, and augmenting sun protection with polypodium leucotomos. Overall, regardless of which niche in dermatology you practice in, there are sure to be exciting therapeutic advancements coming your way.
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