Shots: 

• Atopic dermatitis remains one of the most common inflammatory skin diseases, affecting more than 230M people across the globe. Characterized by frequent itching and recurrent skin lesions, atopic dermatitis is a chronic condition 

• Recently the Lancet published data from Galderma’s P-III trial, ARCADIA 1 and ARCADIA 2, demonstrating the potential of nemolizumab to improve skin lesions, itch, and sleep disturbance in adolescent and adult patients with moderate-to-severe atopic dermatitis 

• Today at PharmaShots, we have Christophe Piketty from Galderma shedding light on nemolizumab  

Saurabh: Could you walk us through the design of the ARCADIA 1 and 2 trials? Who were the patients involved? 

Christophe: The ARCADIA program included two identically designed pivotal phase III clinical trials, ARCADIA 1 and ARCADIA 2, which enrolled more than 1,700 patients. ARCADIA 1 and 2 are global, randomized, multicenter, double-blind, placebo-controlled phase III clinical trials, which evaluated the efficacy and safety of nemolizumab administered subcutaneously every four weeks compared to placebo, both administered with background topical corticosteroids (TCS) with or without topical calcineurin inhibitors (TCI). The trials were conducted in adolescent and adult patients with moderate-to-severe atopic dermatitis for an initial treatment phase of 16 weeks. Although not included in The Lancet publication, the ARCADIA trials also included a maintenance treatment period from Week 16 to Week 48. 

Saurabh: The results indicate that nemolizumab made a significant impact on skin lesions, itch, and sleep disturbance by Week 16. Can you elaborate on these improvements and why they matter for patients? 

Christophe: Data from the ARCADIA 1 and 2 trials support the potential of nemolizumab +TCS/TCI to be an effective treatment that improves three core signs and symptoms of atopic dermatitis: skin lesions, itch, and sleep disturbance. These signs and symptoms impact patients’ quality of life. People living with atopic dermatitis have a risk of developing mental health disorders, and studies show that more than a third of patients report that their condition causes them to avoid social interactions. 

Saurabh: Since we saw significant relief from itch as early as one week after starting treatment, can you talk about how quickly nemolizumab works and how this fast relief might affect patients' daily lives? 

Christophe: Nemolizumab is the first monoclonal antibody specifically designed to target the IL-31 receptor alpha and inhibit IL-31 signaling, which is directly involved in itch. Itch impacts people living with atopic dermatitis: 74% of people living with atopic dermatitis report itch as among their two most burdensome symptoms. Most patients experience sleep disturbance due to chronic itch and are at risk of developing mental health disorders such as anxiety, depression and cognitive dysfunction. The ARCADIA 1 and 2 trials showed that patients not only experienced clinically meaningful improvements in itch, but that they came as early as one week after nemolizumab +TCS/TCI treatment initiation – which is encouraging, given its burden on patients’ quality of life. 

Saurabh: What’s the current status of the Biologics License Application for nemolizumab with the FDA, and what are the next steps we should expect in the approval process? 

Christophe: Our Biologics License Applications for nemolizumab for the treatment of adolescents and adults with moderate-to-severe atopic dermatitis, as well as prurigo nodularis, were accepted by the U.S. FDA for review in February 2024, with nemolizumab being granted Priority Review for prurigo nodularis. We look forward to the U.S. FDA’s decisions on these applications by the end of the year. If approved for the treatment of atopic dermatitis, we are hopeful that nemolizumab +TCS/TCI could be an effective treatment that supports patients in achieving rapid itch relief, while also improving skin lesions and sleep disturbance. Our filing applications for these indications have also been accepted for review by the European Medicines Agency, Health Canada, and the Access Consortium. Submissions to other regulatory authorities are ongoing. 

Saurabh: Looking beyond atopic dermatitis, are there any plans to investigate nemolizumab for other conditions driven by IL-31 signaling, and what potential future applications do you see for this treatment? 

Christophe: We have also investigated nemolizumab in prurigo nodularis, a chronic, debilitating neuroimmune skin disease characterized by the presence of intense itch and thick skin nodules covering large body areas. Results from the OLYMPIA clinical trial program – the largest phase III clinical trial program completed to date, and the only program to include an open-label, long-term extension study in prurigo nodularis – have shown that nemolizumab as a monotherapy significantly improved itch, skin nodules, and sleep disturbance in adult patients with prurigo nodularis, demonstrating a fast onset of action on itch. We believe in the potential for nemolizumab to support patients with itch-related skin conditions and are currently assessing other potential indications for nemolizumab, dedicating our efforts to exploring areas with unmet treatment needs where nemolizumab could have the greatest impact on patients. 

Saurabh: There are multiple small molecules being assessed & available in ADs, how will a biologic make a difference in a small molecule-driven therapy? 

Christophe: Biologics are the most commonly used treatments for moderate-to-severe atopic dermatitis patients who are refractory to topical treatment, and there remains a need for effective treatments that directly address the underlying disease mechanisms in atopic dermatitis. 

Nemolizumab is the first monoclonal antibody specifically inhibiting IL-31 cytokine signaling, designed to address the underlying cause of the most burdensome symptom for people with atopic dermatitis – itch. Primary results from ARCADIA 1 and 2 now published in The Lancet support nemolizumab’s rapid action on itch in atopic dermatitis within one week of treatment and show that patients receiving nemolizumab +TCS/TCI may simultaneously experience improvements in skin lesions, itch and sleep disturbance after four months of treatment. 

Furthermore, results from an analysis of the maintenance phase presented as a late-breaker at the 2024 American Academy of Dermatology congress showed that nemolizumab (when administered with +TCS/TCI) maintains itch and skin responses in atopic dermatitis when dosing once every eight weeks. Results indicated that the majority of patients treated with nemolizumab +TCS/TCI who responded at Week 16 (defined as patients who achieved an IGA score of clear (0) or almost-clear (1), or a 75% or greater improvement in the EASI score) maintained skin and itch responses through to Week 48, with similar efficacy observed whether receiving nemolizumab +TCS/TCI every four or eight weeks. 

Saurabh: As mentioned, the FDA decision on nemolizumab is expected by the end of 2024. Assuming a positive outcome, when can we expect the product to be available on the market? 

Christophe: We are fully committed to bringing nemolizumab to patients as soon as possible, once it has been approved for use. 

Image Source: Canva 

About the Author: 

Christophe Piketty 

Dr. Piketty is a board-certified Dermatologist and Clinical Immunologist and has been Global Program Head at Galderma since 2018. He has extensive expertise in the development of topical compounds and systemic drugs, including biologics, from proof of concept to phase 3 in dermatology. 

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