혈관주위 상피세포종양(PEComa) : 시장 인사이트, 역학 및 시장 예측(-2032년)

Key Highlights:

• In 2022, the market size of PEComa was highest in the US among the 7MM, accounting for approximately USD 20 million, which is further expected to increase by 2032.
• The total number of incident cases of PEComa in the United States was around 250 cases in 2022 and are projected to increase during the forecasted period (2023-2032).
• Aadi Bioscience's FYARRO is the only approved therapy for PEComa.
• In May 2022, Aadi Bioscience reported it received notification of a product-specific, permanent J-code for FYARRO (sirolimus protein-bound particles for injectable suspension) (albumin-bound) for intravenous use for the treatment of adult patients with locally advanced unresectable or metastatic malignant PEComa. Under the Healthcare Common Procedure Coding System (HCPCS), the J-code (J9331) became effective on July 1, 2022.
• High-cost pricing of FYARRO could also be a setback for the drug but apart from that FYARRO aims to address a broad range of solid tumors with TSC1 or TSC2 mutations.
• Currently, there is no emerging drug in the pipeline targeting PEComa. However, the dynamics of the PEComa market might change in the coming years owing to quicker diagnosis and improved awareness of the disease.

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

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

Geography Covered:

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

Study Period: 2019-2032

PEComa Disease Understanding and Treatment Algorithm

PEComa Overview

Perivascular epithelioid cell neoplasms (PEComas) are rare soft tissue tumors. They often form around small blood vessels (perivascular spaces) in various body parts such as the lungs, GI tract, kidneys, liver, and uterus. PEComas are made up of cells with an epithelioid (cuboidal) shape and share some features with melanocytes and smooth muscle cells. Melanocytes are cells normally found in the skin and produce melanin to give skin its color.

PEComa can make some of the same proteins that are used to create pigment. PEComa also makes some of the same proteins found in smooth muscle cells, which make up muscles that are not under one's conscious control, such as the muscles that make up one's internal organs and digestive tract.

According to the WHO classification, in the PEComa NOS, both benign PEComa NOS, as well as clinically challenging tumors with a higher degree of malignancy, are included (malignant PEComa NOS). A malignant PEComa encountered by clinical oncologists in their practice is abdominopelvic perivascular epithelioid cell sarcoma - the so-called malignant PEComa (Sobiborowicz et al., 2020).

PEComas are considered a group of tumors. However, within this group are specific tumors with unique features and more likely to form in certain body parts. These specific tumors include:

• Angiomyolipomas (AMLs),
• Clear cell sugar tumors (CCT)
• Primary extrapulmonary sugar tumor (PEST),
• Lymphangioleiomyomatosis (LAM),
• Clear-cell myomelanocytic tumor (CCMT) of the falciform ligament/ligamentum teres,
• Primary cutaneous PEComa (CCCMT-cutaneous clear cell myomelanocytic tumor), and
• PEComas not otherwise specified (NOS)

PEComa Diagnosis

PEComas may be detected by imaging with X-ray, CT scan, or MRI. Once a tumor is detected, a biopsy is needed to examine the cellular make-up and distinguish it from other tumors.

Tissue samples from biopsies will have a characteristic appearance under the microscope to identify tumors as PEComas and differentiate them from other potential tumors.

PEComas typically have mostly epithelioid cells around blood vessels. They also contain protein markers similar to melanocytes (melanin-producing cells) and smooth muscle cells.

Malignant PEComas can be detected from biopsy as well. Malignancy is more likely in larger PEComas, begin to grow into surrounding tissues, and have a higher percentage of cells that are actively growing.

Genetic testing is available to identify patients with TSC who are at an increased risk of developing PEComas.

For patients with LAM, a blood test for detecting increased levels of vascular endothelial growth factor D (VEGF-D) may aid in diagnosing this PEComa subtype. VEGF-D stimulates the growth of new blood vessels, and high levels may be involved in tumor spread.

Further details are provided in the report

PEComa Treatment

The treatment for localized PEComa is wide surgical resection, and no consensus guidelines exist for systemic therapy in localized disease. Apart from a single robust response to cytotoxic chemotherapy (doxorubicin and ifosfamide), reporting an 80% reduction in tumor size in a patient with extremity soft-tissue PEComa, other cases utilizing cytotoxic chemotherapy regimens for localized PEComa have reported either tumor progression while on therapy or the presence of viable residual tumor following resection. Little clinical or pathologic information exists for neoadjuvant radiation alone in PEComas, but it can be managed like other localized high-grade sarcomas. As in most STS subtypes, the role of adjuvant chemotherapy treatment for PEComa is unclear. Reports on anthracycline-based regimens given adjuvantly in patients with resected PEComa describe disease recurrence in most cases, with a median follow-up of fewer than 2 years.

Nearly 20% of newly diagnosed patients present with metastatic disease, and approximately 70% of patients with localized malignant PEComa will develop metastases. However, given the unpredictable natural history of PEComa, certain patients, especially in cases with isolated/oligometastatic disease or a long recurrence-free period, may benefit from surgical resections of metastatic disease, which could offer long-term disease-free periods and effective disease control.

Traditional cytotoxic chemotherapy regimens in STS have consistently shown little efficacy in advanced PEComa. No objective responses were reported with anthracycline-based regimens, ifosfamide, paclitaxel, gemcitabine, or dacarbazine.

Further details are provided in the report

PEComa Epidemiology

As the market is derived using a patient-based model, the PEComa epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by total incident cases of PEComa, PEComa cases by Gender, Stage, Clinical Presentation, and Age in the 7MM covering the United States, EU4 countries (Germany, France, Italy, and Spain), United Kingdom, and Japan from 2019 to 2032.

• The total number of incident cases of PEComa in the United States was around 250 cases in 2022 and are projected to increase during the forecasted period (2023-2032).
• The United States contributed to the largest incident population of PEComa, acquiring ~64% of the 7MM in 2022. Whereas EU4 and the UK, and Japan accounted for around 28% and 8% of the total population share, respectively, in 2022.
• Among the EU4 countries, Germany accounted for the largest number of PEComa cases, followed by France, whereas Spain accounted for the lowest number of cases in 2022.
• According to DelveInsight estimates, there were around 150 patients in benign stage and less than 100 patients with malignant PEComa in the United States in 2022. The incidence is projected to increase during the forecasted period.
• In 7MM, approximately 70% of the patient share is attributed to females, whereas only 30% of males suffer from PEComa.

PEComa Drug Chapters

The drug chapter segment of the PEComa report encloses a detailed analysis of PEComa marketed drugs and late-stage (Phase III and Phase II) pipeline drugs. It also helps understand the PEComa 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.

Marketed Drugs

FYARRO (sirolimus protein-bound): Aadi Bioscience

FYARRO (sirolimus protein-bound particles for injectable suspension) (albumin-bound) is a prescription medicine used to treat locally advanced unresectable or metastatic malignant PEComa in adult patients. FYARRO had been designed to fight cancer cells. In advanced malignant PEComa, perivascular epithelioid cells grow out of control. FYARRO blocks one of the signals in the cancer cells causing it to grow out of control, helping to stop cancer from growing or spreading. It is a targeted cancer treatment and not a chemotherapy treatment.

FYARRO (sirolimus protein-bound) is different from other mTOR inhibitors because it uses nanoparticle technology to help FYARRO get more of the drug inside tumors to help turn more mTOR switches off.

The misdiagnosis and low awareness of PEComa might not have swift changes for several years and would certainly hinder the market growth for FYARRO. High-cost pricing could also be a setback for the drug. However, the customer-facing team and education program could change the situation for significant market growth in the coming years. The drug is bound to be welcomed by doctors as the only approved therapy for patients with advanced malignant PEComa. FYARRO aims to address a broad range of solid tumors with TSC1 or TSC2 mutations, leading to a significant value for the FYARRO franchise since the initial estimates are that approximately 12,000 patients in the United States carry these gene alterations.

Drug Class Insights

The existing PEComa treatment is mainly dominated by classes such as Anthracycline-based regimens, Gemcitabine-based chemotherapy, VEGFR inhibitors, mTOR inhibitors, and systemic therapies and radiotherapy.

mTOR has long been known as an important target in cancer, and drugs approved from this class include sirolimus, everolimus, etc. However, these drugs did not become as widely accepted as initially hoped. Limitations were driven primarily by poor PK (how the drug acts in the body), inadequate absorption (highly variable), narrow therapeutic index (cannot up the dose to get an optimal amount of drug into the tumor), and poor target suppression. Thus, with FYARRO (nab-sirolimus), management hopes to finally deliver on the broad potential of mTOR inhibition by overcoming all of these limitations (can get very high drug levels into the tumor and have a very wide therapeutic index and therefore greater target suppression and ultimately better efficacy). Versus other mTOR inhibitors, nab-sirolimus has a very long half-life and, in order of magnitude, higher tumor penetration. They have almost complete suppression at the target level, which is impossible to achieve with other mTOR inhibitors.

The drug (FYARRO) is on the market as of February 2022, and the launch is off to a strong start, with more penetration expected in the first line of the setting. Acceptance of clinical profile has been strong across the oncology community in the US (the most differentiating feature is the durability of responses, which is not seen with first-generation mTOR inhibitors). The safety profile is predictable and manageable.

PEComa Market Outlook

Among systemic therapies, mTOR inhibitors are the most frequently used across different lines, either as a curative intent treatment combined with a radical treatment (surgery or radiotherapy) or in the palliative setting. However, as of today, there is no clear recommendation, and the question remains to be answered of whether it can or cannot be considered the gold standard for all patients or only for a subgroup of patients, such as TSC2-mutated patients.

Since PEComas are ultrarare, it is usually challenging to get any commercial pharma interest to pursue them. We have not given the market of surgery. Currently, there is no emerging drug in the pipeline targeting PEComa. However, the dynamics of the PEComa market might change in the coming years owing to quicker diagnosis and improved awareness of the disease. Pricing policies must also be considered to achieve great success in PEComa; this will further help launch an attractive product appropriate to the market. All these factors will help build a strong market-fit product.

• The total market size of PEComa in the 7MM is approximately USD 20 million in 2022 and is projected to increase during the forecast period (2023-2032).
• Among EU4 countries, Germany accounts for the maximum market size in 2022, while Spain occupies the bottom of the ladder in 2022.
• In 2022, the US accounted for the maximum share of the total market in the 7MM, i.e., approximately 90%, followed by EU4 and the UK in 2022.

KOL Views

To keep up with current market trends, we take KOLs and SME's opinions working in the domain through primary research to fill the data gaps and validate our secondary research. Industry Experts contacted for insights on PEComa evolving treatment landscape, patient reliance on conventional therapies, patient's therapy switching acceptability, and drug uptake along with challenges related to accessibility, include Medical/scientific writers, Medical Oncologists, and Professors, Department of Medical Oncology, Strasbourg-Europe Cancer Institute, Dana-Farber Cancer Institute, and others.

Delveinsight's analysts connected with 50+ KOLs to gather insights; however, interviews were conducted with 15+ KOLs in the 7MM. Centers such as MD Anderson Cancer Center, Texas from UT Southwestern Medical Center in Dallas, Cancer Research UK Barts Centre in London, MD Anderson Cancer Center etc., were contacted. Their opinion helps understand and validate current therapy treatment patterns or PEComa 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 analyzes 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.

In efficacy, the trial's primary and secondary outcome measures are evaluated; for instance, in PEComa trials, one of the most important primary outcome measures is the overall survival (OS), progression free survival (PFS), duration of response(DoR), and overall response rate (ORR).

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 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.

FYARRO (sirolimus protein-bound particles for injectable suspension) received notification of a product-specific, permanent J-code (albumin-bound) for intravenous use for the treatment of adult patients with locally advanced unresectable or metastatic malignant PEComa. Under the Healthcare Common Procedure Coding System (HCPCS), the J-code (J9331) came into effect on July 1, 2022. J-codes are permanent, product-specific reimbursement codes assigned to outpatient and physician-administered "buy and bill" products under Medicare Part B and are used by commercial insurers and government payers to facilitate and standardize claims submissions and reimbursements for medications like FYARRO (also known as nab-sirolimus). When the permanent J-code goes into effect, all hospital outpatient departments, ambulatory surgery centers, and physician offices in the United States will have one consistent Healthcare Common Procedure Coding System (HCPCS) code to standardize the submission and payment of FYARRO insurance claims across Medicare, Medicare Advantage, Medicaid and commercial plans.

Scope of the Report:

• The report covers a segment of key events, an executive summary, descriptive overview of PEComa, explaining its causes, signs and symptoms, pathogenesis, 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 with treatment guidelines.
• Additionally, an all-inclusive account of the current therapies that will have an impact on the current treatment landscape and upcoming market.
• A detailed review of the PEComa 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 preference that help in shaping and driving the 7MM PEComa market.

PEComa Report Insights

• Patient Population
• Therapeutic Approaches
• PEComa Market Size and Trends
• Existing and future Market Opportunity

PEComa Report Key Strengths

• Ten Years Forecast
• 7MM Coverage
• PEComa Epidemiology Segmentation
• Key Cross Competition
• Attribute analysis
• Drugs Uptake and Key Market Forecast Assumptions

PEComa Report Assessment

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

Key Questions

Market Insights:

• What was the PEComa total market size, the market size by therapies, market share (%) distribution in 2019, and what would it look like in 2032? What are the contributing factors for this growth?
• How will mTOR inhibitors as a class affect the treatment paradigm in PEComa?
• What kind of uptake mTOR inhibitor will FYARRO witness PEComa patients in the coming 10 years?
• Which class is going to be the largest contributor in 2032?
• What are the pricing variations among different geographies for approved and off-label therapies?
• How would the market drivers, barriers, and 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 PEComa? What will be the growth opportunities across the 7MM with respect to the patient population pertaining to PEComa?
• What is the historical and forecasted PEComa patient pool in the United States, EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan?
• Which type of molecular aletrations associated with PEComas contributes the most in patients affected with PEComa?
• What is the contribution of benign and malignant cases in total incident cases PEComa?

Current Treatment Scenario, Marketed Drugs, and Emerging Therapies:

• What are the current options for the treatment of PEComa? What are the current treatment guidelines for the treatment of PEComa in the US and Europe?
• What are the recent novel therapies, targets, mechanisms of action, and technologies developed to overcome the limitation of existing therapies?
• What is the reimbursement scenario of the approved therapies for PEComa?
• What is the cost burden of approved therapies on the patient?
• Patient acceptability in terms of preferred treatment options as per real-world scenarios?
• What are the country-specific accessibility issues of expensive, recently approved therapies?
• What are the 7MM historical and forecasted market of PEComa?

Reasons to buy:

• The report will help in developing business strategies by understanding the latest trends and changing treatment dynamics driving the PEComa Market.
• Insights on patient burden/disease incidence, 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.
• 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.
• Highlights of Access and Reimbursement policies of approved therapies, barriers to accessibility of expensive off-label therapies, and patient assistance programs.
• 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.

Table of Contents

1. Key Insights

2. Report Introduction

3. Executive Summary

4. Key Events

5. Epidemiology and Market Forecast Methodology

6. PEComa Market Overview at a Glance in the 7MM

• 6.1. Market Share (%) Distribution by Class of Therapies in 2022
• 6.2. Market Share (%) Distribution by Class of Therapies in 2032

7. Disease Background and Overview

• 7.1. Introduction
  • 7.1.1. Subtypes of PEComas
  • 7.1.2. Signs and symptoms
  • 7.1.3. Causes
  • 7.1.4. Risk assessment
  • 7.1.5. Pathomorphology
• 7.2. Diagnosis
  • 7.2.1. Immunohistochemistry
• 7.3. Differential Diagnosis

8. Treatment

• 8.1.1. Localized disease
• 8.1.2. Advanced disease

9. Guidelines

• 9.1. National Comprehensive Cancer Network Clinical Practice Guidelines for PEComa (2022)
• 9.2. ESMO-EURACAN Clinical Practice Guidelines for Soft Tissue Sarcoma (2018)

10. Epidemiology and Patient Population

• 10.1. Key Findings
• 10.2. Assumption and Rationale
• 10.3. Total Incident Cases of PEComa in the 7MM
• 10.4. US
  • 10.4.1. Total Incident Cases of PEComa in the US
  • 10.4.2. PEComa Cases by Gender in the US
  • 10.4.3. PEComa Cases by Stage in the US
  • 10.4.4. PEComa Cases by Clinical Presentation in the US
  • 10.4.5. PEComa Cases by Age in the US
• 10.5. EU4 and the UK
  • 10.5.1. Total Incident Cases of PEComa in EU4 and the UK
  • 10.5.2. PEComa Cases by Gender in EU4 and the UK
  • 10.5.3. PEComa Cases by Stage in EU4 and the UK
  • 10.5.4. PEComa Cases by Clinical Presentation in EU4 and the UK
  • 10.5.5. PEComa Cases by Age in EU4 and the UK
• 10.6. Japan
  • 10.6.1. Total Incident Cases of PEComa in Japan
  • 10.6.2. PEComa Cases by Gender in Japan
  • 10.6.3. PEComa Cases by Stage in Japan
  • 10.6.4. PEComa Cases by Clinical Presentation in Japan
  • 10.6.5. PEComa Cases by Age in Japan

11. Patient Journey

12. Key Endpoints in PEComa

13. Marketed Drugs

• 13.1. Key Cross of Current Therapies
• 13.2. FYARRO (sirolimus protein-bound/ABI-009): Aadi Bioscience
  • 13.2.1. Product description
  • 13.2.2. Regulatory milestones
  • 13.2.3. Other development activities
  • 13.2.4. Safety and efficacy

14. PEComa: 7MM Analysis

• 14.1. Key Findings
• 14.2. Total Market Size of PEComa in the 7MM
• 14.3. Market Size of PEComa by Therapies in the 7MM
• 14.4. Market Outlook
  • 14.4.1. Where It All Began: How sirolimus became nab-sirolimus (FYARRO)
• 14.5. The US Market Size
  • 14.5.1. Total Market Size of PEComa in the US
  • 14.5.2. Market Size of PEComa by First-line Therapies in the US
  • 14.5.3. Market Size of PEComa by Second-line and Above Therapies in the US
• 14.6. EU4 and the UK Market Size
  • 14.6.1. Total Market Size of PEComa in EU4 and the UK
  • 14.6.2. Market Size of PEComa by First-line Therapies in EU4 and the UK
  • 14.6.3. Market Size of PEComa by Second-line and above Therapies in EU4 and the UK
• 14.7. Japan Market Size
  • 14.7.1. Total Market Size of PEComa in Japan
  • 14.7.2. Market Size of PEComa by First-line Therapies in Japan
  • 14.7.3. Market Size of PEComa by Second-line and above Therapies in Japan

15. Unmet Needs

16. SWOT Analysis

17. KOL Views

• 17.1. KOL Interview

18. Market Access and Reimbursement

• 18.1. United States
  • 18.1.1. Centre for Medicare and Medicaid Services (CMS)
• 18.2. EU4 and the UK
  • 18.2.1. Germany
  • 18.2.2. France
  • 18.2.3. Italy
  • 18.2.4. Spain
  • 18.2.5. United Kingdom
• 18.3. Japan
  • 18.3.1. MHLW
• 18.4. Market Access and Reimbursement: PEComa
  • 18.4.1. Centre for Medicare and Medicaid Services (CMS)
  • 18.4.2. Financial support for patients

19. Appendix

• 19.1. Bibliography
• 19.2. Report Methodology

20. DelveInsight Capabilities

21. Disclaimer

22. About DelveInsight