Neurofibromatosis type 1-associated Plexiform Neurofibromas (NF1-PN) - Market Insights, Epidemiology, and Market Forecast - 2034

Key Highlights:

• In 2023, the total diagnosed prevalent cases of NF1 were around 97,000 in the US, and these cases are anticipated to increase by 2034. The rise in NF1 cases can be attributed to improved awareness, advancements in diagnostic techniques, and increased genetic testing accessibility.
• Plexiform neurofibromas are identified in about 30 to 50% of NF1 via whole-body MRI.
• As pediatric NF1 patients transition to adulthood, they will likely need support in shifting from pediatric care, typically provided by a pediatrician or neurooncologist, to an adult neurooncologist and care team. This transition can be challenging, especially for patients with cognitive difficulties and the added burden on caregivers.
• Surgery remains a standard treatment for many patients, but it is often complex, not always feasible, carries inherent risks, and has a high likelihood of recurrence. Additionally, some plexiform neurofibromas are deemed inoperable.
• The lack of disease-modifying treatments for pediatric NF1 patients with symptomatic, inoperable PNs, aside from surgery, severely impacts their quality of life. This includes issues like pain, reduced motor function, cognitive challenges, psychosocial struggles, and the potential for social stigma due to the visible appearance of the tumors.
• NF1 management in Japan relies mainly on supportive care, with analgesics and NSAIDs as the most common treatments. The findings highlight significant unmet needs, economic burdens, and the urgent demand for innovative treatment options.
• The need for multidisciplinary and specialized care in NF1-PN treatment highlights potential equity challenges, particularly due to geographical disparities across the 7MM.
• The availability of medical therapy as an alternative to surgery adds new dimensions to clinical decision-making and management strategies.
• The approval of KOSELUGO has transformed the treatment of children with inoperable NF1-PN tumors. Building on this progress, researchers are now exploring other MEK inhibitors for potential use in both pediatric and adult patients.
• KOSELUGO is only approved for pediatric patients but not adults, creating a treatment gap. Mirdametinib, in mid-stage trials, aims for approval in both pediatric and adult populations. Promising data from mirdametinib's Phase IIb ReNeu trial show significant tumor shrinkage and sustained improvements in quality of life for both pediatric and adult patients.
• Other MEK inhibitors like FCN-159 and early-stage candidate PAS-004 are under development, offering enhanced dosing and tolerability profiles.
• Emerging therapies aim to improve administration ease and minimize side effects, addressing current treatment limitations.
• PAS-004, with a 70-h half-life, offers the potential for once-daily dosing, unlike first-generation MEK inhibitors requiring twice-daily dosing and having shorter half-lives (<8 h).
• The evolving NF1-PN treatment landscape features clinical trials led by SpringWorks Therapeutics, Healx, and Fosun Pharmaceutical, along with university-sponsored trials in this patient segment.

DelveInsight's "NF1-PN - Market Insights, Epidemiology and Market Forecast - 2034" report delivers an in-depth understanding of the NF1-PN, historical and forecasted epidemiology as well as the NF1-PN market trends in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.

The NF1-PN market report provides current treatment practices, emerging drugs, market share of individual therapies, and current and forecasted 7MM NF1-PN market size from 2020 to 2034. The report also covers current NF1-PN treatment practices/algorithms and unmet medical needs to curate the best of the opportunities and assess the underlying potential of the market.

Geography Covered:

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

Study Period: 2020-2034

NF1-PN Disease Understanding and Treatment Algorithm

NF1-PN Overview

NF1 is the most common tumor predisposition syndrome, caused by mutations in the NF1 gene, which leads to the loss of neurofibromin, a regulator of RAS activity. This results in the development of plexiform neurofibromas, peripheral nerve sheath tumors that cause significant morbidity in affected patients. Historically, surgery was the primary treatment for plexiform neurofibromas, but many tumors are inoperable or carry substantial surgical risks. With a better understanding of the genetic basis of plexiform neurofibromas, targeted therapies, such as the MEK inhibitor KOSELUGO, have emerged as promising options, particularly for pediatric patients with symptomatic, inoperable plexiform neurofibromas. Treatment for NF1-PN is highly individualized, with options including surgery, medical therapies, and watchful waiting. Decisions are guided by a multidisciplinary team, considering factors like tumor size, location, impact on surrounding tissues, and patient and family preferences.

NF1-PN Diagnosis

NF1-PN is often identified in early childhood, usually through visible signs such as cafe-au-lait spots or subtle tissue overgrowth. However, deeply situated plexiform neurofibromas can remain undetected until symptoms like pain emerge, requiring imaging for diagnosis. These tumors are complex, infiltrating surrounding tissues and posing challenges due to their irregular shapes and overvascularization. Plexiform neurofibromas often develop in critical areas, including the head, neck, chest, or spine, complicating surgical treatment and increasing risks such as bleeding. Diagnosis requires vigilance for early signs, timely imaging, and specialist input. A multidisciplinary approach involving genetics, neurology, radiology, and surgery is crucial for managing the disease's physical and emotional impact on pediatric patients and their families.

NF1-PN Treatment

Treating NF1-associated plexiform neurofibromas requires a multidisciplinary team, including dermatologists, oncologists, neurologists, surgeons, and orthopedists. Surgery can improve function or appearance but is often challenging due to tumor regrowth, involvement with vital structures, and bleeding risks from overvascularization. KOSELUGO, a MEK inhibitor approved by the FDA (2020) and EMA (2021) for children with NF1-PN, offers potential benefits but shows variable results. Radiation therapy is rarely used due to risks like malignant transformation into MPNST or worsening vascular issues. Early detection and personalized care are essential for effective management.

NF1-PN Epidemiology

The NF1-PN epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by total diagnosed prevalent cases of NF1, diagnosed prevalent cases of NF1 manifestations, and age-specific diagnosed prevalent cases of NF1-PN, NF1-PN cases by clinical symptoms, NF1-PN cases eligible for surgery in the 7MM covering the United States, EU4 (Germany, France, Italy, and Spain), United Kingdom, and Japan from 2020 to 2034.

• Among the 7MM, the US accounted for the highest number of cases in 2023, with around 39,000 diagnosed prevalent cases of NF1-PN. These cases are expected to increase during the forecast period.
• Among EU4 and the UK, the highest number of cases of NF1-PN was found in Germany whereas the UK accounted for the lowest cases in 2023.
• In the US, around 30% of the NF1-PN cases accounted for children, whereas 70% of the cases accounted for adults in 2020.
• In the Japan, there were 5,500 operable cases and 3,900 inoperable cases of NF1-PN in 2023. These cases are expected to increase during the forecast period.

Neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN) Chapters

The drug chapter segment of the NF1-PN report encloses a detailed analysis of the marketed, mid and early-stage (Phase III, Phase II, and Phase I/II) pipeline drugs. The marketed drugs segment encloses only KOSELUGO. The current emerging candidates are mirdametinib, HLX-1502, and FCN-159. The drug chapter also helps understand the NF1-PN clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details, and the latest news and press releases.

For example, in April 2024, Healx announced that it had signed an investment agreement with its long-term partner, the Children's Tumor Foundation (CTF).

Marketed Drugs

KOSELUGO (selumetinib): AstraZeneca and Merck

KOSELUGO is an inhibitor of MEK1/2. KOSELUGO blocks specific enzymes (MEK1 and MEK2), which are involved in stimulating cells to grow. In NF1, these enzymes are overactive, causing tumor cells to grow in an unregulated way. By blocking these enzymes, KOSELUGO slows down the growth of tumor cells. In April 2020, the FDA approved KOSELUGO for pediatric patients aged 2 and older with symptomatic, inoperable plexiform neurofibromas associated with NF1. In June 2021, the EU granted conditional approval for KOSELUGO in pediatric patients aged 3 and older with symptomatic, inoperable PN. In September 2022, Japan approved KOSELUGO for children aged 3 and older with clinically symptomatic PN that cannot be fully surgically removed without significant risk of morbidity. The drug has been granted ODD, BTD, and Rare Pediatric Disease Designation.

In November 2024, AstraZeneca and Merck announced positive topline results from the Phase III KOMET trial in adults with NF1 who have symptomatic, inoperable plexiform neurofibromas, and the companies plan to share these findings with regulatory authorities and present them at an upcoming medical meeting.

Emerging Drugs

Mirdametinib: SpringWorks Therapeutics

Mirdametinib is an investigational oral, allosteric, small-molecule MEK inhibitor in development as a monotherapy treatment for NF1-PN and Low-grade Glioma (LGG) and as a combination therapy for the treatment of several subsets of biomarker-defined metastatic solid tumors. It was designed to inhibit MEK1 and MEK2, which occupy pivotal positions in the MAPK pathway.

As per the Q3 presentation in November 2024, SpringWorks Therapeutics states the progress towards potential European regulatory approval in 2025. In August 2024, SpringWorks Therapeutics announced that the US FDA accepted the Company's NDA, which was submitted in July 2024, for mirdametinib for the treatment of adult and pediatric patients with NF1-PN. The NDA was granted Priority Review and has been given a PDUFA action date of February 28, 2025.

HLX-1502: Healx

HLX-1502 is a tablet taken orally that works differently than other treatments and offers a new and differentiated investigational treatment option for patients with NF1. Healx has secured the US FDA clearance for an Investigational New Drug application (IND) to commence a Phase II clinical trial of HLX-1502, targeting adults with NF1 and inoperable plexiform neurofibroma. Recently, in October 2024, Healx announced that the US FDA granted FTD to HLX-1502 for the treatment of NF1.

Drug Class Insights

MEK Inhibitors

NF1-associated plexiform neurofibromas present significant treatment challenges, often being inoperable or prone to regrowth. MEK inhibitors have established themselves as an effective treatment class for NF1-associated plexiform neurofibromas. With limited therapeutic options available, many adults with NF1-PN suffer from significant functional impairments and debilitating symptoms that profoundly affect their quality of life. Clinical evidence underscores KOSELUGO's potential to transform patient care by significantly reducing the size of plexiform neurofibromas. AstraZeneca and MSD's KOSELUGO, a MEK1/2 inhibitor, is the first and only FDA-approved therapy proven to reduce plexiform neurofibroma size in pediatric NF1 patients.

The MEK inhibitors that are in clinical trials include mirdametinib from SpringWorks Therapeutics and FCN-159 from Fosun Pharmaceutical. Additionally, innovative companies like Pasithea Therapeutics are expanding the pipeline with PAS-004, their proprietary MEK inhibitor. PAS-004 is an early-stage candidate. These developments represent a key advancement in managing NF1-PN, offering hope for more effective and less invasive therapies in the future.

NF1-PN Market Outlook

The treatment landscape for NF1-PN has historically been limited to surgical interventions, primarily complete resection or debulking. The tumors' size and location often complicate these approaches, with many being classified as inoperable due to their proximity to vital structures or their invasive nature. Approximately 50% of patients with NF1-PN face tumors that cannot be safely removed without significant risk of morbidity, necessitating a focus on symptomatic management rather than curative surgery.

Surgical options remain the gold standard for NF1-PN when feasible. Complete resection is ideal but rarely achievable due to the complex anatomy of these tumors, which often intertwine with nerves and blood vessels. Debulking, or partial removal, may alleviate symptoms but does not guarantee long-term relief, as these tumors frequently regrow. The decision to proceed with surgery is contingent upon a thorough evaluation of the tumor's characteristics and the patient's overall. The approval of KOSELUGO, a selective MEK1/2 inhibitor, marks a pivotal change in the treatment paradigm for pediatric patients with symptomatic, inoperable NF1-PN in 2020. KOSELUGO is currently the first and only FDA-approved therapy specifically indicated for this condition.

The landscape for treating NF1-PN is evolving rapidly as research continues to uncover the genetic underpinnings of these tumors. Emerging drugs like mirdametinib (SpringWorks Therapeutics), HLX-1502 (Healx), and FCN-159 (Fosun Pharmaceutical) are gaining significant attention in the treatment of NF1-PN, offering promising new avenues for patients with inoperable or symptomatic tumors. The launch of these therapies is expected to create a positive impact on the market.

• The total market size of NF1-PN in the 7MM was around USD 380 million in 2023. This is estimated to increase by 2034.
• Among the 7MM, the US consistently captured the highest market of about USD 230 million in 2023, which is anticipated to grow during the forecast period.
• Among EU4 and the UK, the highest market share for NF1-PN was found in Germany, which was estimated to be nearly 32 million of the market share in EU4 and the UK in 2023.
• Among the forecasted emerging therapies, mirdametinib is expected to capture the highest market in the 7MM by 2034.

NF1-PN Uptake

This section focuses on the rate of uptake of the potential drugs expected to be launched in the market during the study period 2020-2034. Mirdametinib is an investigational oral, allosteric, small-molecule MEK inhibitor in development as a monotherapy treatment developed by SpringWorks Therapeutics, anticipated to enter the market in 2025. Mirdametinib holds a first-mover advantage, particularly for adult patients, as no approved therapies currently exist for this population. Mirdametinib is positioning itself for approval in both pediatric and adult NF1-PN patients, setting it apart from other treatments that are primarily focused on children. This broader patient applicability strengthens mirdametinib's potential to lead in the market

NF1-PN Pipeline Development Activities

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

SpringWorks Therapeutics, Healx, and Fosun Pharmaceutical are actively evaluating their pipeline candidates for the treatment of NF1-PN in clinical trials.

Pipeline Development Activities

The report covers detailed information on collaborations, acquisitions and mergers, licensing, and patent details for NF1-PN emerging therapies.

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 NF1-PN's evolving treatment landscape, patient reliance on conventional therapies, patient's therapy switching acceptability, and drug uptake along with challenges related to accessibility, include KOL from Children's Tumour Foundation, Associate Professor, Washington University School of Medicine in Saint Louis, Associate Professor, Cardiff University, and others.

Delveinsight's analysts connected with 30+ KOLs to gather insights. However, interviews were conducted with 10+ KOLs in the 7MM. Their opinion helps to understand and validate current and emerging therapies and treatment patterns or NF1-PN market trends. This will support the clients in potential upcoming novel treatments by identifying the overall scenario of the market and the unmet needs.

Qualitative Analysis

We perform Qualitative and market Intelligence analysis using various approaches, such as SWOT analysis, 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 is done to analyze multiple approved and emerging therapies based on relevant attributes such as safety, efficacy, frequency of administration, route of administration, and order of entry. Scoring is given based on these parameters to analyze the effectiveness of therapy.

Further, the therapies' safety is evaluated wherein the acceptability, tolerability, and adverse events are majorly observed, and 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

The United States

OneSource Personalized Patient Support From Alexion

OneSource is a free, personalized patient support program offered by Alexion. Whether the patient is newly diagnosed or has had their condition for some time, the specialists are available for patients and their caregivers. The support can help them make sense of their health insurance coverage, answer questions about treatment with KOSELUGO, and connect them to community resources.

At OneSource, a team of specialists are trained in NF1 and are ready to give patients the support they deserve-whatever their care plan may be.

Alexion KOSELUGO CoPay Program

The Alexion KOSELUGO CoPay program pays for eligible out-of-pocket medication with KOSELUGO up to USD 26,000 US dollars per calendar year. After reaching the maximum program benefit, the patient will be responsible for any remaining out-of-pocket costs incurred during that calendar year.

The report further provides detailed insights on the country-wise accessibility and reimbursement scenarios, cost-effectiveness scenario of approved therapies, programs making accessibility easier and out-of-pocket costs more affordable, insights on patients insured under federal or state government prescription drug programs, etc.

Scope of the Report:

• The report covers a segment of key events, an executive summary, and a descriptive overview of NF1-PN, explaining its causes, signs and symptoms, and currently available therapies.
• Comprehensive insight has been provided into the epidemiology segments and forecasts, the future growth potential of diagnosis rate, disease progression, along treatment guidelines.
• Additionally, an all-inclusive account of both the current and emerging therapies, along with the elaborative profiles of mid-stage and prominent therapies, will have an impact on the current treatment landscape.
• A detailed review of the NF1-PN 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 and expert insights/KOL views, patient journey, and treatment preferences that help in shaping and driving the NF1-PN market.

NF1-PN Report Insights

• Patient Population
• Therapeutic Approaches
• NF1-PN Pipeline Analysis
• NF1-PN Market Size and Trends
• Existing and future Market Opportunity

NF1-PN Report Key Strengths

• 11 Years Forecast
• 7MM Coverage
• NF1-PN Epidemiology Segmentation
• Key Cross Competition
• Conjoint analysis
• Drugs Uptake and Key Market Forecast Assumptions

NF1-PN Report Assessment

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

FAQs:

• What was the NF1-PN market size, the market size by therapies, market share (%) distribution in 2023, and what would it look like by 2034? What are the contributing factors for this growth?
• What are the pricing variations among different geographies for approved therapies?
• What can be the future treatment paradigm of NF1-PN?
• What are the disease risks, burdens, and unmet needs of NF1-PN? What will be the growth opportunities across the 7MM concerning the patient population with NF1-PN?
• Who is the major competitor of KOSELUGO in the market?
• Which class performed better and generated the highest revenue in 2024?
• What are the current options for the treatment of NF1-PN? What are the current guidelines for treating NF1-PN in the US, Europe, and Japan?
• What are the recent novel therapies, targets, mechanisms of action, and technologies being developed to overcome the limitations of existing therapies?

Reasons to Buy:

• The report will help in developing business strategies by understanding the latest trends and changing treatment dynamics driving the NF1-PN 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
• To understand the existing market opportunity in varying geographies and the growth potential over the coming years.
• Distribution of historical and current patient share based on real-world prescription data along with reported sales of approved products in the US, EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan.
• Identification of strong upcoming players in the market will help in devising strategies that will help in getting 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.
• Highlights of Access and Reimbursement policies of approved therapies, barriers to accessibility of off-label expensive therapies, and patient assistance programs.
• To understand the perspective of Key Opinion Leaders around the accessibility, acceptability, and compliance-related challenges of existing treatment to overcome barriers in the future.
• Detailed insights on the unmet needs of the existing market so that the upcoming players can strengthen their development and launch strategy.