Breakthrough Clinical Results
AbCellera presented preclinical data on ABCL575, a half-life extended anti-OX40L monoclonal antibody for moderate-to-severe atopic dermatitis. The data showed potent inhibition of inflammatory pathways, favorable pharmacokinetics, and potential for less frequent dosing. The drug is expected to enter Phase 1 clinical trials in 2025.
Key Highlights
- Potent inhibition of inflammatory pathways in preclinical studies.
- Favorable pharmacokinetics and potential for less frequent dosing.
- Positive nonclinical safety profile.
- Expected entry into Phase 1 clinical trials in 2025.
Incidence and Prevalence
Global Epidemiology of Atopic Dermatitis
Several studies provide estimates of the incidence and prevalence of atopic dermatitis (AD) globally, with varying results depending on the methodology and year of publication. Here's a summary of some of the latest findings:
2021 Estimates:
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A study published in 2023, using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, estimated that in 2021 there were 260 million (95% UI 227-298) individuals with asthma and 129 million (124-134) individuals with atopic dermatitis worldwide. While this study provides the number of cases, it also notes a decrease in age-standardized prevalence rates for both conditions. Specifically for AD, the age-standardized prevalence rate decreased by 8.3% from 1990 to 2021, from 1885.4 per 100,000 to 1728.5 per 100,000. The study forecasts an increase in cases to 275 million for asthma and 148 million for AD by 2050, driven by population growth, but expects age-standardized prevalence rates to remain stable.
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Another study published in 2023, focusing specifically on children aged 0 to 14 years, found that global pediatric AD cases reached 72.4 million (95% uncertainty interval: 68.5-76.5) in 2021, a 6.2% increase from 2000. However, the prevalence rate decreased on average by 0.15% annually. This study highlights regional variations, with the highest rates in Central Asia, high-income Asia Pacific, and Western Europe, and the lowest in Sub-Saharan Africa.
2019 Estimates:
- A study published in 2022, using data from the GBD 2019 study, estimated the global prevalence of AD to be 2.6% (95% UI 1.9-3.5), affecting approximately 204 million people. This study also provided separate estimates for adults (2.0% prevalence, 101 million people) and children (4.0% prevalence, 103 million people). It highlighted variations by sex, with a higher prevalence in females (2.8%) than males (2.4%).
Other Estimates:
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A meta-analysis published in 2023 reported a point prevalence of 11.1% (95% CI 9.4-13.1) in children and adolescents, and 6.3% (95% CI 5.0-7.8) in adults. This study included 310 studies with 25.5 million individuals.
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A 2018 study reported a global age-standardized prevalence of AD in 2017 of 2.23%, affecting at least 171 million individuals.
Key Considerations:
- Variations in methodology: Different studies use different diagnostic criteria, data sources, and statistical methods, leading to variations in estimates.
- Age and sex: AD prevalence is generally higher in children than adults and varies between males and females.
- Geographic distribution: AD prevalence varies substantially across different regions of the world, with higher rates observed in developed countries and certain regions like Central Asia and Western Europe.
- Time trends: While some studies report increasing trends in AD prevalence, others show stable or decreasing age-standardized rates. It's important to consider both the absolute number of cases and the age-standardized rates when interpreting trends.
It's important to note that these are just a few examples, and other studies may provide different estimates. For the most up-to-date information, it's recommended to consult the latest publications and reports on AD epidemiology.
Emerging Mechanism of Action
KnolQuest, developed by Pienomial LLC, summarizes key mechanisms of action (MoA) emerging for atopic dermatitis (AD) treatment based on recent PubMed publications:
1. Targeting Type 2 Inflammation:
- IL-4/IL-13 Inhibition: This MoA aims to block the signaling of IL-4 and IL-13, key cytokines driving type 2 inflammation in AD. Dupilumab, a monoclonal antibody targeting the shared IL-4 receptor alpha subunit, has shown significant efficacy in reducing AD signs and symptoms. Other IL-13 specific inhibitors like lebrikizumab and tralokinumab have also demonstrated promising results in clinical trials.
- IL-31 Inhibition: IL-31 is a cytokine involved in pruritus (itch) in AD. Nemolizumab, a monoclonal antibody targeting the IL-31 receptor, has shown efficacy in reducing itch and improving skin lesions in AD.
- OX40-OX40L Pathway Inhibition: This pathway plays a role in T-cell activation and inflammation. Rocatinlimab (anti-OX40) and amlitelimab (anti-OX40L) are being investigated for their potential to modulate T-cell responses and reduce AD severity.
2. Janus Kinase (JAK) Inhibition:
- JAK inhibitors block the activity of JAK enzymes, which are involved in cytokine signaling and inflammation. Several oral JAK inhibitors, including baricitinib (JAK1/2), upadacitinib (JAK1), and abrocitinib (JAK1), have demonstrated efficacy in moderate-to-severe AD. Topical JAK inhibitors, such as ruxolitinib cream and delgocitinib ointment, are also being developed for milder forms of AD.
3. Phosphodiesterase 4 (PDE4) Inhibition:
- PDE4 inhibitors block the activity of PDE4 enzymes, which are involved in the breakdown of cyclic adenosine monophosphate (cAMP), a molecule that regulates inflammation. Crisaborole, a topical PDE4 inhibitor, is approved for mild-to-moderate AD in patients 2 years and older. Difamilast, another topical PDE4 inhibitor, has shown promising results in clinical trials.
4. Aryl Hydrocarbon Receptor (AhR) Modulation:
- Tapinarof is a topical AhR modulating agent that has shown efficacy in reducing AD signs and symptoms. The exact mechanism of action is not fully understood, but it is thought to involve modulation of immune responses and skin barrier function.
5. Restoring Skin Barrier Function:
- EpiCeram, a ceramide-dominant barrier repair formulation, has shown efficacy in improving skin barrier function and reducing AD symptoms. It contains a combination of ceramides, cholesterol, and fatty acids that mimic the natural composition of the skin barrier.
These MoAs represent the current focus of AD research and drug development. Ongoing and future clinical trials will further elucidate their efficacy, safety, and potential role in personalized AD treatment.
Drug used in other indications
ABCL575 (Rademikibart) is primarily being investigated for atopic dermatitis (AD). While the provided text mentions numerous biologics and other treatments for AD, it doesn't specify other indications for which ABCL575 is currently being trialed, nor the intervention models for those trials. The text does mention that ABCL575 blocks IL-4Rα-mediated signal transduction, similar to dupilumab, and that it has shown promising results in a phase I trial for AD, with rapid and sustained improvements in AD severity and quality of life. However, without more information, it's impossible to determine what other conditions it might be effective for. To find out more about ongoing trials for ABCL575, it's recommended to search clinical trial databases like ClinicalTrials.gov using the drug's name or other identifiers.