Netherton Syndrome - Market Insight, Epidemiology And Market Forecast - 2032

Key Highlights:

• The diagnosed prevalence of Netherton syndrome has been increasing in the US due to increased population and awareness.
• There is no approved therapy to treat Netherton syndrome. The management of Netherton syndrome involves a multidisciplinary approach and aims to alleviate symptoms; current treatment includes moisturizers, topical corticosteroids, topical vitamin D (calcipotriol), anti-inflammatory agents, calcineurin inhibitors (pimecrolimus and tacrolimus), retinoids, immunosuppressants, and others.
• Non-pharmacological therapies, such as cleansing the skin with a gentle/soft non-detergent liquid cleansing oil for daily baths and/or showers, are recommended. Additionally, a narrowband UVB (NB-UVB) phototherapy and psoralen-UVA (PUVA) photochemotherapy are methods often used for the treatment.
• The pathogenesis of Netherton syndrome is well understood, with a definite link to mutations in the SPINK5 gene that have led to the discovery of potential pathways like IL-7 and KLK inhibition.
• Ongoing research to discover better diagnostic techniques has identified new imaging techniques that surpass diagnostic challenges like time consumption and surgical removal of skin samples with a skin biopsy.
• The major concern in understanding the market for Netherton syndrome is a lack of epidemiology data and a paucity of evidence to validate interventions used in the daily management of Netherton syndrome. Further, the lack of established diagnostic and treatment guidelines for Netherton syndrome results in variability and therapy uncertainty.
• In 2022, the market size of Netherton syndrome was highest in the US among the 7MM countries, accounting for approximately USD 16.02 million. It is expected to increase by 2032.
• Among current therapies, topical calcineurin inhibitors, medications that are often used to treat inflammatory skin conditions, suppress the immune response, and reduce inflammation in the skin, generating a revenue of USD 9.61 million in the US, capturing nearly 60% of the total Netherton syndrome market in 2022.
• The available treatment is limited to symptom relief with unproven efficacy and unwanted side effects like Cushing syndrome, skin damage, and others.
• Advances in research have led to the discovery of novel molecules, like small peptide-based inhibitors, monoclonal antibodies, and gene therapy that may offer effective options to treat and manage Netherton syndrome.
• Emerging therapies QRX003 and SPEVIGO can potentially create a positive shift in the market size of Netherton syndrome during the forecast period.
• Quoin Pharmaceuticals' QRX003 is a topical serine protease inhibitor applied once daily. It performs the function of the missing LEKTI protein and down-regulates the activity of the kallikreins. The Invisicare technology implemented enables the drug to stay longer on the surface and impart adequate penetration in the skin without systemic absorption. It is projected to enter the US market by 2025.
• Boehringer Ingelheim's SPEVIGO is a monoclonal IgG1 antibody that antagonizes IL-36R. The IL-36 pathway plays a vital role in inflammation; hence the therapy can potentially address the needs of Netherton syndrome.
• Preclinical studies have yielded gene therapy and other KLK inhibitors; conducting further research and clinical trials may offer effective and curative therapy. Since there is a lack of approved therapy, pharma players can bring novel therapies to cure and manage Netherton syndrome.

DelveInsight's "Netherton Syndrome - Market Insights, Epidemiology, and Market Forecast - 2032" report delivers an in-depth understanding of the Netherton syndrome historical and forecasted epidemiology as well as the market trends in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.

The Netherton syndrome market report provides current treatment practices, emerging drugs, market share of individual therapies, and current and forecasted the 7MM Netherton syndrome market size from 2019 to 2032. The report also covers current Netherton syndrome treatment practices/algorithms and unmet medical needs to curate the best opportunities and assess the market's potential.

Geography Covered:

• The United States
• EU4 (Germany, France, Italy, and Spain) and the United Kingdom
• Japan

Study Period: 2019-2032.

Netherton Syndrome Understanding and Treatment Algorithm

Netherton Syndrome Overview

Netherton syndrome is a rare and severe genetic autosomal recessive disorder of ichthyosis. It is an inherited skin condition, often present at birth or in the first few weeks of life, where the skin is very red with fine dry scales.

The condition lasts for a lifetime, but the severity can vary from person to person. The syndrome is also known as Comel-Netherton syndrome and is characterized by a clinical triad of Ichthyosis Linearis Circumflexa (ILC), trichorrhexis invaginata, or bamboo hair, atopic manifestations, and multisystemic complications.

Bamboo hair, indicates hair shaft abnormalities, while atopic diathesis includes frequent asthma and allergies. Further, ichthyosiform erythroderma presents inflamed, red, scaly skin.

Netherton syndrome usually occurs at birth or becomes apparent shortly after with symptoms including generalized erythroderma, pruritus, and scaling. Patients may also experience recurrent infections, growth retardation, and impaired quality of life.

Netherton syndrome occurs due to loss of function mutations in the serine peptidase inhibitor kazal type 5 (SPINK5) gene that encodes a serine peptidase inhibitor, lympho-epithelial kazal-type-related inhibitor (LEKTI). Losing LEKTI leads to dysregulation of epidermal proteases and severe skin barrier impairment. Kallikrien-related peptidases, such as KLK7, and the epidermal elastase 2 (ELA2), which LEKTI inhibits, are reported to play major roles in Netherton syndrome pathology.

Netherton Syndrome Diagnosis

The diagnosis of Netherton syndrome is often difficult in early infancy because of the clinical presentation of erythroderma with failure to thrive, common with other conditions, such as other immune deficiency syndromes.

The disease is diagnosed using a combination of clinical examination, family history analysis, and skin biopsy. For SPINK5 mutations, molecular genetic testing is usually used for confirmation. Identifying a germline SPINK5 mutation by DNA sequencing supports the diagnosis; however, the cost of performing DNA sequencing analysis limits its use in diagnosis. Further, Differential diagnoses include peeling skin syndrome, Omenn syndrome and other primary immune deficiency syndromes, hyper IgE syndromes, severe atopic and severe skin dermatitis, multiple allergies, metabolic wasting (SAM) syndrome, and others.

Further details related to country-based variations are provided in the report…

Netherton Syndrome Treatment

The management of Netherton syndrome is multidisciplinary and aims to alleviate symptoms rather than solve the root cause. There is no approved therapy to treat Netherton syndrome. The current symptomatic therapies include emollients, keratolytic, and moisturizers to hydrate the skin, topical corticosteroids to reduce inflammation, itching, and redness, topical vitamin D (calcipotriol) to reduce excessive scaling and inflammation, calcineurin inhibitors like pimecrolimus and tacrolimus for modulating the immune response and reducing inflammation.

Besides these retinoids, immunosuppressants (topical and systemic), other anti-inflammatory agents are also used. Biologics are used off-label, but their efficacy is not yet established. However, long-term use of most of the therapies is associated with safety concerns as they may be linked to skin atrophy, irritation, and recurrent infection.

Along with these pharmacological therapies, daily showers with non-detergent liquid cleansing oil with an acidic pH to counteract overactive serine proteases, especially during acute flares, bleach baths with sodium hypochlorite diluted in water, and narrowband UVB (NB-UVB) phototherapy and psoralen-UVA (PUVA) photochemotherapy are also recommended.

Netherton Syndrome Epidemiology

As the market is derived using a patient-based model, the Netherton syndrome epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by diagnosed prevalent cases of Netherton syndrome and gender-specific cases of Netherton syndrome in the 7MM covering the United States, EU4 countries (Germany, France, Italy, and Spain) and the United Kingdom, and Japan from 2019 to 2032.

• In 2022, the total diagnosed prevalent cases of Netherton syndrome were estimated to be approximately 3,454 cases in the 7MM. These cases are projected to increase during the forecast period.
• In 2022, among the 7MM, the US accounted for the highest diagnosed prevalent cases of Netherton syndrome, contributing nearly 49%, while Japan accounted for the least with nearly 4% of the total diagnosed prevalent cases.
• In the US, there were approximately 1,687 diagnosed prevalent cases of Netherton syndrome in 2022. These cases are expected to increase by 2032.
• In 2022, Germany ranked first among EU4 and the UK, with approximately 422 diagnosed prevalent cases of Netherton syndrome, followed by France and the UK with nearly 342 and 339 cases, respectively. The total cases in EU4 and the UK are expected to increase by 2032.
• In EU4 and the UK, among the gender-specific cases of Netherton syndrome, there were 685 males and 959 females in 2022. These cases are expected to increase by 2032.
• Among EU4 and the UK, Germany accounted for the highest number of females (246) affected by Netherton syndrome in 2022, followed by France, the UK, and others.

In Japan, there were around 124 cases of Netherton syndrome in 2022, out of which nearly 57% of the cases were diagnosed in females, while 43% were in males.

Netherton Syndrome Drug Chapters

The drug chapter segment of the Netherton syndrome report encloses a detailed analysis of Netherton syndrome, currently used drugs, and late-stage (Phase II/III) pipeline drugs. It also helps understand the Netherton syndrome clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details, advantages and disadvantages of each included drug, and the latest news and press releases.

Emerging Drugs:

QRX003: Quoin Pharmaceuticals

QRX003 is a once-daily topical lotion comprised of a broad-spectrum serine protease inhibitor formulated with the proprietary in-licensed Invisicare technology. The active ingredient in QRX003 performs the function of the missing LEKTI protein and down-regulates; however, it does not completely stop the activity of the kallikreins, leading to a more normalized skin-shedding process and the formation of a stronger and more effective skin barrier. Further, the serine protease inhibitor in QRX003 is a potent anti-inflammatory and antioxidant.

QRX003 is being tested in Phase II/III clinical studies as a potential treatment for Netherton syndrome patients who are currently receiving off-label systemic therapy. Additionally, the company is developing QRX003 in other dermatological diseases, including peeling skin syndrome, SAM Syndrome, and palmoplantar keratoderma. Quoin is also investigating QRX007 in preclinical studies as a potential therapy for Netherton syndrome at Queensland University of Technology, Australia.

Drug Class Insights

Current treatment approaches for Netherton syndrome are limited to symptom relief or supportive care with marginal efficacy and undesirable side effects. A gentle/soft non-detergent liquid cleansing oil, preferably with an acidic pH to counteract overactive serine proteases, is recommended for daily baths and/or showers. Several classes of drugs are being used to manage Netherton syndrome, including emollients, antihistamines, topical corticosteroids, calcineurin inhibitors, calcipotriol, retinoids, immunoglobulins, antibiotics, and others.

Netherton Syndrome Market Outlook

Netherton syndrome, a form of congenital ichthyosis, is a debilitating rare skin disorder that occurs due to a mutation in the SPINK5 gene that causes the lack of LEKTI protein that ultimately results in multiple abnormalities, including defective keratinization, severe skin barrier defects, and hair anomalies, resulting from an excessive serine protease activity. Further, patients also suffer from a pronounced predisposition to allergies, asthma, skin cancers, eczema, severe dehydration, an inability to regulate their body temperature, and chronic skin inflammation. Neonates can be severely affected by the condition, which can be fatal, and fail to gain weight and grow at the expected rate. It is usually diagnosed by examining clinical history, symptoms, and skin biopsy.

The current market has been covered by various symptomatic treatment options used across the 7MM. Topical calcineurin inhibitors and other therapies, including retinoids, IVIGs, biologics, and corticosteroids, were the major drug classes considered for the current treatment in the forecast model.

Key players Quoin Pharmaceuticals (QRX003), Boehringer Ingelheim (SPEVIGO [spesolimab/BI 655130]), LifeMax Laboratories, and Novartis' (LM-030 [BPR277]), and others are evaluating their lead candidates in different stages of clinical development. They aim to investigate their products for the treatment of Netherton syndrome.

• The total market size of Netherton syndrome in the 7MM was approximately USD 24.60 million in 2022 and is projected to increase during the forecast period (2023-2032).
• According to DelveInsight's estimates, among the 7MM, the US had the largest market share for Netherton syndrome, with a revenue of nearly USD 16.02 million in 2022, and will increase during the study period due to increasing awareness of the disease and the launch of the emerging therapies.
• Among EU4 and the UK countries, Germany accounted for the maximum market size of Netherton syndrome in 2022, followed by France, and the UK, while Spain occupied the bottom of the ladder.
• Japan captured the lowest market share of Netherton syndrome among the 7MM, with a revenue of approximately USD 0.77 million in 2022, expected to change during the forecast period.
• In the US, among the current therapies, the topical calcineurin inhibitors market accounted for around USD 9.61 million in 2022.
• Though the pipeline is limited, a few therapies that, include QRX003 and SPEVIGO (spesolimab/BI 655130), will enter the market during the forecast period.
• QRX003 is a topical serine protease inhibitor applied once daily. It performs the function of the missing LEKTI protein and down-regulates the activity of the kallikreins. It is projected to enter the US market by 2025, generating a revenue of USD 0.42 million in the same year.
• In the US, SPEVIGO (spesolimab/BI 655130) is expected to enter by 2027 and is expected to attain a peak in its 7th year.

Netherton Syndrome Drugs Uptake

This section focuses on the uptake rate of potential drugs expected to be launched in the market during 2019-2032. For example, SPEVIGO (spesolimab/BI 655130) is a monoclonal IgG1 antibody that antagonizes IL-36R. It is anticipated to enter the US market by 2027 and is predicted to have a medium uptake during the forecast period.

Further detailed analysis of emerging therapies drug uptake in the report…

Netherton Syndrome Pipeline Development Activities

The report provides insights into therapeutic candidates in Phase II/III, Phase II, and Phase I. It also analyzes key players involved in developing targeted therapeutics.

Pipeline Development Activities

The report covers information on collaborations, acquisitions and mergers, licensing, and patent details for emerging therapies for Netherton syndrome.

KOL Views:

To keep up with current market trends, we take KOLs and SMEs' opinions working in the domain through primary research to fill the data gaps and validate our secondary research. Industry Experts contacted for insights on the Netherton syndrome evolving treatment landscape, patient reliance on conventional therapies, patient therapy switching acceptability, and drug uptake, along with challenges related to accessibility, including Medical/scientific writers, Medical Professionals, Professors, Directors, and Others.

DelveInsight's analysts connected with 50+ KOLs to gather insights; however, interviews were conducted with 15+ KOLs in the 7MM. Centers like the University of California, the Foundation for Ichthyosis & Related Skin Types, the Institute of Human Genetics, St John's Institute of Dermatology, Ormond Street Hospital, and the Juntendo University Shizuoka Hospital were contacted. Their opinion helps understand and validate current and emerging therapy treatment patterns or Netherton syndrome market trends. This will support the clients in potential upcoming novel treatments by identifying the overall scenario of the market and the unmet needs.

Physician's View:

According to our primary research analysis, though there is a lack of treatment guidelines and approved therapies, the commonly prescribed pharmacological treatments are emollients, topical antimicrobials, calcineurin inhibitors, and steroids, while other treatments are rarely used. Further, pimecrolimus is a calcineurin inhibitor widely used to manage inflammation. In case of an increased risk of skin infections, antibiotics or antiseptics may be prescribed to prevent or treat infections. In severe cases, systemic therapies such as oral retinoids or immunomodulatory medications might be considered to manage widespread inflammation and skin symptoms. However, these treatments have potential side effects. There is a need to improve disease awareness and develop targeted, effective, and well-tolerated therapies.

Qualitative Analysis:

We perform Qualitative and market Intelligence analysis using various approaches, such as SWOT and Conjoint Analysis. In the SWOT analysis, strengths, weaknesses, opportunities, and threats in terms of disease diagnosis, patient awareness, patient burden, competitive landscape, cost-effectiveness, and geographical accessibility of therapies are provided. These pointers are based on the Analyst's discretion and assessment of the patient burden, cost analysis, and existing and evolving treatment landscape.

Conjoint Analysis analyzes multiple emerging therapies based on relevant attributes such as safety, efficacy, frequency of administration, route of administration, and order of entry. The effectiveness of these therapies was analyzed based on scores in the reduction in the Investigator's Global Assessment (IGA) from baseline, change in total body surface area affected by Netherton, change in Ichthyosis Area Severity Index response, and reduction in Netherton syndrome sign.

The therapies' safety is evaluated wherein the acceptability, tolerability, and adverse events are majorly observed. It sets a clear understanding of the side effects posed by the drug in the trials. In addition, the scoring is also based on the route of administration, order of entry and designation, probability of success, and the addressable patient pool for each therapy. According to these parameters, the final weightage score and the ranking of the emerging therapies are decided.

Market Access and Reimbursement:

Reimbursement of rare disease therapies can be limited due to lack of supporting policies and funding, challenges of high prices, lack of specific approaches to evaluating rare disease drugs given limited evidence, and payers' concerns about budget impact. The high cost of rare disease drugs usually has a limited effect on the budget due to the small number of eligible patients being prescribed the drug. The US FDA has approved several rare disease therapies in recent years. From a patient perspective, health insurance and payer coverage guidelines surrounding rare disease treatments restrict broad access to these treatments, leaving only a small number of patients who can bypass insurance and pay for products independently.

Several organizations are working to provide support to Netherton syndrome patients and spread awareness across the 7MM, including the First Skin Foundation (the US), Selbsthilfe Ichthyose e.V. (Germany), Association Icthyose (France), European Network of Ichthyosis, the Netherton Syndrome Group (the UK), Ichthyosis Support Group (the UK), Asociacion Espanola de Ictiosis (Spain), and others.

Scope of the Report:

• The report covers a segment of key events, an executive summary, descriptive overview of Netherton syndrome, explaining its causes, signs and symptoms, pathogenesis, and currently available therapies.
• Comprehensive insight into the epidemiology segments and forecasts, the future growth potential of diagnosis rate, disease progression, and treatment guidelines have been provided.
• Additionally, an all-inclusive account of the current and emerging therapies and the elaborative profiles of late-stage and prominent therapies will impact the current treatment landscape.
• A detailed review of the Netherton syndrome market, historical and forecasted market size, market share by therapies, detailed assumptions, and rationale behind our approach is included in the report, covering the 7MM drug outreach.
• The report provides an edge while developing business strategies, by understanding trends, through SWOT analysis, expert insights/KOL views, patient journey, and treatment preferences that help shape and drive the 7MM Netherton syndrome market.

Netherton Syndrome Report Insights

• Patient Population
• Therapeutic Approaches
• Netherton Syndrome Pipeline Analysis
• Netherton Syndrome Market Size and Trends
• Existing and Future Market Opportunity

Netherton Syndrome Report Key Strengths

• 10 Years Forecast
• The 7MM Coverage
• Netherton Syndrome Epidemiology Segmentation
• Key Cross Competition
• Conjoint Analysis
• Drugs Uptake and Key Market Forecast Assumptions

Netherton Syndrome Report Assessment

• Current Treatment Practices
• Unmet Needs
• Pipeline Product Profiles
• Market Attractiveness
• Qualitative Analysis (SWOT and Conjoint Analysis)

Key Questions:

Market Insights

• What was the total market size of Netherton syndrome, the market size of Netherton syndrome by therapies, market share (%) distribution in 2019, and what would it look like by 2032? What are the contributing factors for this growth?
• How will QRX003 and SPEVIGO (spesolimab/BI 655130) affect the Netherton syndrome treatment paradigm?
• How will current therapies compete with other emerging therapies?
• Which drug is going to be the largest contributor by 2032?
• What are the pricing variations among different geographies for off-label therapies?
• How would future opportunities affect the market dynamics and subsequent analysis of the associated trends?

Epidemiology Insights

• What are the disease risk, burdens, and unmet needs of Netherton syndrome? What will be the growth opportunities across the 7MM with respect to the patient population pertaining to Netherton syndrome?
• What is the historical and forecasted patient pool of Netherton syndrome in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan?
• Out of the countries mentioned above, which country would have the highest diagnosed prevalent Netherton syndrome population during the forecast period (2023-2032)?
• What factors are contributing to the growth of Netherton syndrome cases?

Current Treatment Scenario, Marketed Drugs, and Emerging Therapies

• What are the current options to treat Netherton syndrome?
• How many companies are developing therapies for the treatment of Netherton syndrome?
• How many emerging therapies are in the late, mid, and early stages of development for treating Netherton syndrome?
• What are the recent novel therapies, targets, mechanisms of action, and technologies developed to overcome the limitation of existing therapies?
• What is the cost burden of current treatment on the patient?
• Patient acceptability in terms of preferred treatment options as per real-world scenarios?
• What are the accessibility issues of approved therapy in the US?
• What is the 7MM historical and forecasted market of Netherton syndrome?

Reasons to Buy:

• The report will help develop business strategies by understanding the latest trends and changing treatment dynamics driving the Netherton syndrome market.
• Insights on patient burden/disease prevalence, evolution in diagnosis, and factors contributing to the change in the epidemiology of the disease during the forecast years.
• Understand the existing market opportunity in varying geographies and the growth potential over the coming years.
• The distribution of historical and current patient share is based on real-world prescription data in the US, EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan.
• Identifying strong upcoming players in the market will help devise strategies to help get ahead of competitors.
• Detailed analysis and ranking of class-wise potential current and emerging therapies under the conjoint analysis section to provide visibility around leading classes.
• To understand Key Opinion Leaders' perspectives around the accessibility, acceptability, and compliance-related challenges of existing treatment to overcome barriers in the future.
• Detailed insights on the unmet need of the existing market so that the upcoming players can strengthen their development and launch strategy