Recent Developments in Aesthetics

Study: Melanoma No Longer the Leading Cause of Skin Cancer Deaths

Non-melanoma skin cancer (NMSC) is causing a greater number of global deaths than melanoma, according to a new study presented at the European Academy of Dermatology and Venerology (EADV) Congress 2023 in Berlin, Germany.

Researchers also believe that NMSC is underreported and that the true impact of this disease may be even higher than estimated.

Although NMSC is less likely to be fatal than melanoma skin cancer, its prevalence is strikingly higher. In 2020, NMSC accounted for 78% of all skin cancer cases, resulting in over 63,700 deaths. By contrast, melanoma caused an estimated 57,000 fatalities in the same year.

“The significantly higher incidence of NMSC has, therefore, led to a more substantial overall impact,” says study author Professor Thierry Passeron, MD, PhD, a professor and the chair of the Department of dermatology at the Université Côte d’Azur in Nice, France, in a news release.

Professor Passeron adds, “As alarming as these figures are, they may be underestimated. NMSC is often underreported in cancer registries, making it challenging to understand the true burden.”

In addition to examining the overall burden of skin cancers, the researchers identified specific population groups that were more at risk of this disease, including people who work outside, organ transplant recipients, and those who have the skin condition xeroderma pigmentosum.

The study, which utilized data from the World Health Organization International Agency for Research on Cancer, found a high incidence of skin cancer in fair-skinned and elderly populations from the USA, Germany, the UK, France, Australia, and Italy. However, even countries with a high proportion of dark phenotypes were not immune to the risk of death from skin cancer, as demonstrated by the registered 11,281 deaths in Africa.

In 2020, there were nearly 1.2 million reported cases of NMSC worldwide compared with 324,635 cases of melanoma. The majority of skin cancer occurrences are non-melanoma, referring to a group of cancers that slowly develop in the upper layers of the skin, with common types including basal cell carcinoma and squamous cell carcinoma. In comparison with melanoma, a type of skin cancer that develops in the melanocytes, NMSC is less likely to spread to other parts of the body and can be treated more easily.

Professor Passeron adds, “We have to get the message out that not only melanoma can be fatal, but NMSC also. It’s crucial to note that individuals with melanin-rich skin are also at risk and are dying from skin cancer. There is a need to implement effective strategies to reduce the fatalities associated with all kinds of skin cancers.”

The new study did not find consistent evidence to suggest that having more dermatologists per capita could reduce mortality rates. Countries like Australia, the UK, and Canada, with fewer dermatologists, exhibited low mortality-to-incidence ratios.

“We therefore need to explore what strategies these countries are employing to reduce the impact of skin cancer in further depth,” he says. “The involvement of other healthcare practitioners, such as GPs, in the identification and management of this disease may partly explain their success. There remains a huge opportunity worldwide to elevate the role of GPs and other healthcare professionals in this process and train them to recognize suspicious lesions early.”

There is an ongoing need to develop awareness campaigns that educate the general public about the risks of sun exposure and other relevant risk factors, according to Professor Passeron.

“These campaigns should be tailored to at-risk populations, including those with fair skin, outdoor workers, the elderly, and individuals who are immunosuppressed,” he adds. “Importantly, these efforts should also extend to populations that may not typically be considered at high risk, such as darker-skinned populations.”

Tralokinumab Controls AD Over the Long Term

Continuous use of Leo Pharma’s Adtralza (tralokinumab) provided long-term disease control in adult patients with moderate-to-severe atopic dermatitis (AD), according to a post hoc, interim, subgroup analysis of the ongoing ECZTEND study presented at the European Academy of Dermatology and Venereology (EADV) Congress in Berlin, Germany.

The analysis was of participants from ECZTEND who had previously enrolled in the ECZTRA 1 and 2 phase 3 trials. A total of 347 adult patients using Adtralza for up to four years were included in the analysis. At the end of this period, an Investigator’s Global Assessment score of 0 (clear) or 1 (almost clear) (IGA 0/1) was observed in 52.6% of patients. At least a 75% reduction in the Eczema Area and Severity Index (EASI-75) was observed in 84.5% of patients, and an EASI-90 in 64.4%, the study showed.

The safety profile was consistent with earlier analyses, with no new safety signals arising with continued Adtralza use over the four-year treatment period.

“Long-term disease control is a critical need for patients with atopic dermatitis,” says study author Andrew Blauvelt, MD, a dermatologist and Investigator at Oregon Medical Research Center in Portland, in a news release. “These new long-term data demonstrate that treatment with tralokinumab produces sustained responses that offer real benefits to the people living with this debilitating disease over time.”

Sotyktu Demonstrates Durable Efficacy and Consistent Safety for up to Three Years in Moderate-to-Severe Plaque PsO

Bristol Myers Squibb’s Sotyktu (deucravacitinib) shows durable efficacy and consistent safety for up to three years in people with moderate-to-severe plaque psoriasis, according to research presented at the European Academy of Dermatology and Venereology (EADV) Congress in Berlin, Germany.

Sotyktu is a first-in-class oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor.

At Week 148, clinical response rates were maintained with continuous treatment with modified nonresponder imputation (mNRI) responses of 73.2% for Psoriasis Area and Severity Index (PASI) 75, 48.1% for PASI 90 and 54.1% for static Physician’s Global Assessment (sPGA) 0/1. Moreover, Sotyktu demonstrated a consistent safety profile with no increases in the rates of adverse events (AEs) or serious AEs over time, and no emergence of any new safety signals.

“These new, positive, three-year results reinforce the long-term efficacy and well-established safety profile of once-daily Sotyktu, the first and only TYK2 inhibitor available, and add to our confidence in its role as an oral treatment of choice for adults with moderate-to-severe plaque psoriasis,” says April Armstrong, MD, MPH, clinical investigator in the POETYK PSO clinical trial program and professor and chief of dermatology at the University of California, Los Angeles, in a press release. “For my patients, more days of relief from this chronic disease mean that they can focus on other aspects of their lives, and these POETYK PSO long-term data add to the evidence that we have the ability to offer a new standard of care to patients seeking an oral treatment option.”

The safety analysis assessed 1,519 patients who received at least one dose of Sotyktu across POETYK PSO-1, POETYK PSO-2 and POETYK PSO-LTE. The efficacy analysis assessed 513 patients who received continuous Sotyktu treatment from Day 1 in the pivotal POETYK PSO-1 and POETYK PSO-2 trials and transitioned to the LTE trial. Cumulative exposure from parent trial randomization was 3,294 patient-years (PYs) for the safety analyses.

Clinical efficacy outcomes were maintained in patients who were continuously treated with Sotyktu from baseline through Week 148, with sustained response rates for PASI 75 (Week 16, 61.1%; Week 52, 72.6%; Week 148, 73.2%), PASI 90 (Week 16, 35.2%; Week 52, 45.6%; Week 148, 48.1%) and sPGA 0/1 (Week 16, 57.5%; Week 52, 58.1%; Week 148, 54.1%).

At three years, cumulative exposure-adjusted incidence rates (EAIRs)/100 PYs were similar or decreased compared with rates observed at two years, respectively, for AEs (144.8, 154.4), serious AEs (5.5, 6.1), discontinuation due to AEs (2.4, 2.8), herpes zoster (0.6, 0.7), malignancies (0.9, 0.9), major adverse cardiovascular events (0.3, 0.4), venous thromboembolism (0.1, 0.1) and deaths (0.3, 0.4). EAIRs/100 PYs were calculated as the number of patients with an AE over the total exposure time for all patients at risk (time to an initial AE occurrence for patients with AE and time of total exposure for patients without an AE).

“As the leader in TYK2 innovation, Bristol Myers Squibb continues to advance our long-term understanding of our first-in-class, oral Sotyktu treatment for plaque psoriasis and explore its full potential across serious immune-mediated diseases,” adds Roland Chen, MD, senior vice president and head, Immunology, Cardiovascular and Neuroscience Development, Bristol Myers Squibb. “These new data validate the potential of Sotyktu to provide long-term, clinically relevant improvement for individuals living with moderate-to-severe plaque psoriasis.”

Lebrikizumab Update: IL-13 Blocker Performs Well in AD Inadequately Controlled with Cyclosporine

Lebrikizumab showed clinical improvements in combination with topical corticosteroids (TCS) in adult and adolescent patients with moderate-to-severe atopic dermatitis (AD) that was not adequately controlled with cyclosporine or for whom cyclosporine was not medically advisable, according to research presented at the European Academy of Dermatology and Venereology (EADV) Congress in Berlin.

Patients were assessed over 16 weeks in the Phase 3 ADvantage study. The safety was consistent with the known safety profile of lebrikizumab.

Further data presented at the meeting showed sustained depth of response in patients who participated in the Phase 3 monotherapy Advocate 1 and 2 studies treated with lebrikizumab over 52 weeks. Deep responses, defined as total skin clearance (Investigator’s Global Assessment (IGA), Eczema Area and Severity Index (EASI)100) and itch relief (NRS 0,1), were achieved in 20% and 31% of patients by Week 16 respectively and were maintained or increased through Week 52

Lebrikizumab also provided long-term clinically meaningful responses in patients. In a post-hoc analysis of the ADvocate 1 and 2 studies, 84% of patients who had responded to lebrikizumab at Week 16 achieved a clinically meaningful response in at least one domain of the disease (mild signs, symptoms, or quality of life impact) after 52 weeks, and more than 57% achieved response across the three domains. This represents a status of minimal residual disease.

Improvements in absolute skin response over 16 weeks for patients with moderate-to-severe AD treated with lebrikizumab or placebo were also shared. A post-hoc analysis of the ADvocate1 and ADvocate2 trials showed that, overall, a significantly higher proportion of patients treated with lebrikizumab achieved EASI ≤7 (mild) and EASI ≤1 (clear/almost clear) at Week 16 compared to placebo. This analysis also demonstrated that, regardless of baseline severity, over 50% of patients treated with lebrikizumab 250 mg every other week on monotherapy for 16 weeks achieved an EASI score indicating mild AD and approximately 20% achieved an EASI score indicating clear or almost clear skin.

“Atopic dermatitis is a debilitating chronic skin condition that can be challenging to manage. Cyclosporine A is the only classical systemic treatment approved in Europe for AD, but its safety may limit long-term use, or it may be contraindicated for some patients,” says Professor. Dr. Ricard B. Warren, Professor of Dermatology and Honorary Consultant Dermatologist at the University of Manchester and Northern Care Alliance NHS Foundation Trust and principal investigator of the ADvantage trial, in a news release. “Although there are an increasing number of treatment options available to ease symptoms and improve outcomes of AD, unfortunately, there are few that offer long-term disease control with a favorable safety profile. The results of this trial reinforce our confidence that lebrikizumab is a promising potential new treatment for patients with moderate-to-severe AD, including those not adequately controlled or ineligible for treatment with cyclosporine A.”

“The new lebrikizumab data set presented at the EADV congress provides further evidence of its efficacy and safety profile. Its anticipated addition to the moderate-to-severe AD treatment arsenal is promising news for both healthcare professionals and patients, including those who do not respond adequately to cyclosporine. Our teams are diligently working to increase our level of knowledge and expand the body of evidence, thereby reinforcing the profile of this potential first-line treatment,”, adds Karl Ziegelbauer, PhD, Chief Scientific Officer at Almirall.

Almirall received a positive CHMP opinion in September, recommending marketing authorization for lebrikizumab for the treatment of adult and adolescent patients (12 years and older with a body weight of at least 40 kg) with moderate-to-severe AD who are candidates for systemic therapy.

Almirall has licensed the rights to develop and commercialize lebrikizumab for the treatment of dermatology indications, including AD, in Europe. Eli Lilly and Company has exclusive rights for the development and commercialization of the product in the United States and the rest of the world, not including Europe. Almirall expects regulatory decisions for lebrikizumab in moderate-to-severe AD in additional European markets, including the United Kingdom and Switzerland in 2024.

Eli Lilly and Company recently announced that the U.S. Food and Drug Administration (FDA) has issued a complete response letter for the lebrikizumab biologic license application (BLA) for the treatment of moderate-to-severe atopic dermatitis (eczema). The letter cited findings that arose during a multi-sponsor inspection of a third-party, contract manufacturing organization that included the monoclonal antibody drug substance for Lilly’s lebrikizumab. The letter stated no concerns about the clinical data package, safety, or label for lebrikizumab.