Complement 3 Glomerulopathy Market Insight, Epidemiology and Market Forecast - 2034

Key Highlights

• C3 glomerulopathy (C3G) is a rare kidney disorder characterized by the abnormal buildup of the complement protein C3 in the glomeruli, the filtering units of the kidneys. This excessive complement activation leads to inflammation and damage to kidney tissue, which can result in proteinuria, reduced kidney function, and potentially kidney failure.
• In 2023, there were approximately 5,760 diagnosed prevalent cases of complement 3 glomerulopathies across the 7MM, with the United States representing about 60% of these cases with the highest number of cases in the United States, followed by Germany.
• The market size of C3G in the 7MM was ~USD 35 million in 2023 and is expected to increase by 2034 due to an increase in the diagnosed prevalence of C3G and the entry of emerging therapies with a premium price tag.
• Since there are no approved therapies for C3G, the market is mainly dominated by the use of off-label prescription drugs. Treatments for C3G include immunosuppressants, steroids, renin-angiotensin-aldosterone system inhibitors (RAAS), and other supportive therapies (calcineurin inhibitors, other immunosuppressive agents, and antibodies).
• Upcoming anti-complements such as iptacopan and pegcetacoplan present a realistic therapeutic option for complement-related diseases.
• Adults population is more prevalent towards C3G compared to the pediatric population. Approximately ~15% of the population of C3G in Japan are pediatric and ~85% are adults.

This report delivers an in-depth understanding of Complement 3 Glomerulopathy (C3G), historical and forecasted epidemiology as well as Complement 3 Glomerulopathy (C3G) market trends in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.

The Complement 3 Glomerulopathy market report provides current treatment practices, emerging drugs, market share of individual therapies, and current and forecasted 7MM Complement 3 Glomerulopathy market size from 2020 to 2034. The report also covers current Complement 3 Glomerulopathy 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: 2020-2034

Complement 3 Glomerulopathy Disease Understanding and Treatment Algorithm

Complement 3 Glomerulopathy Overview

The term complement 3 glomerulopathy was adopted by expert consensus in 2013 to define a group of rare kidney diseases driven by dysregulation of the complement cascade. The major features of C3G include high levels of protein in the urine (proteinuria), blood in the urine (hematuria), reduced amounts of urine, low levels of protein in the blood, and swelling in several areas of the body.

C3G is a type of glomerular disease, characterized by predominant C3 complement component (C3) deposits in the glomeruli in the absence of a significant amount of immunoglobulin and without deposition of C1q and C4. The accumulation of C3 without a significant amount of classical or lectin complement component in the glomeruli suggests dysregulation of the alternative complement pathway as the underlying pathogenetic mechanism. This finding, in the absence or near absence of immunoglobulin deposits in a patient with the classic clinical features of glomerulonephritis, is the single diagnostic criterion. The rarity of C3G makes it challenging to derive precise incidence and prevalence of the indication; however, several small cohort studies have generated estimates of limited reliability.

Complement 3 Glomerulopathy Diagnosis

In most cases, diagnosis of C3G requires a renal biopsy and careful review of light microscopy, immunofluorescence, and electron microscopy. Broadly, C3G is defined as the predominant staining of C3 on immunofluorescence (IF) when compared to immunoglobulin (intensity >2 orders of magnitude). C3G is classified by electron microscopy findings into DDD or C3GN, depending on the presence or absence of dense osmiophilic intramembranous deposits. However, the various diagnostic tests opted for establishing a C3G diagnosis are as follows: Urine test, Blood test, Glomerular filtration rate (GFR), and Kidney biopsy.

Complement 3 Glomerulopathy Treatment

Optimal treatment for C3G has not been established yet since no treatment has proven effective and beneficial for C3G. All patients diagnosed with C3G should be treated with renoprotective measures, including lifestyle advice, an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker to control hypertension and proteinuria, and lipid-lowering treatment. Such medication alone has not been shown to protect against progression to end-stage renal disease but may improve the protective effect of immunosuppressive medication. Due to the absence of approved treatment/therapies for C3G as well as therapies that can attack the cause of C3G, the treatment regimen focuses on slowing the process of kidney damage from C3G. This treatment regimen may include corticosteroids (often called “steroids”), immunosuppressive drugs, ACE inhibitors and ARBs, diet changes, and complement inhibitors.

Complement 3 Glomerulopathy Epidemiology

The disease epidemiology covered in the report provides historical as well as forecasted epidemiology segmented by total diagnosed prevalent population of C3G, type-specific diagnosed prevalent population of C3G, and age-specific diagnosed prevalent population of C3G in the 7MM market covering the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom and Japan from 2020 to 2034.

• The total diagnosed prevalent population of C3G in the 7MM was found to be ~5,760 in 2023.
• The diagnosed prevalent population of C3G, in the United States, was found to be 3,372 in 2023.
• In EU4 and the UK, the diagnosed prevalent population of C3G was found to be the maximum in Germany, followed by Spain in 2023. While the lowest number of cases were found in Italy.
• In Japan, adults are more prevalent in C3G compared to pediatrics.

Complement 3 Glomerulopathy Drug Chapters

The drug chapter segment of the Complement 3 Glomerulopathy report encloses a detailed analysis of the marketed and the late-stage (Phase III and Phase II) pipeline drugs. Furthermore, the current key players for emerging drugs and their respective drug candidates include Novartis Pharmaceuticals (Iptacopan), Apellis Pharmaceuticals (pegcetacoplan), and others. The drug chapter also helps understand the Complement 3 Glomerulopathy clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details, and the latest news and press releases.

Emerging Drugs

Iptacopan (LNP023): Novartis Pharmaceuticals

Novartis Pharmaceuticals is developing Iptacopan, which is an oral small-molecule inhibitor of complement factor B (FB) with potential immunomodulatory activity. Upon administration, FB inhibitor LNP023 binds to FB and prevents the formation of the alternative pathway (AP) C3-convertase (C3bBb). This limits the cleavage of C3 to the active fragment C3b and may prevent C3b-mediated extravascular hemolysis in certain complement-driven disorders such as C3G, paroxysmal nocturnal hemoglobinuria (PNH), etc. The company is expecting data read-out in 2025 from the Phase II study (NCT03955445). The initial results from the APPEAR-C3G Phase III trials are anticipated in the second half of 2023.

Furthermore, data read-out from the Phase III study (NCT03955445) is expected by 2025. Novartis plans to submit the drug by 2024, aiming to bring it to market promptly and meet the needs of patients. Iptacopan is expected to have a first-mover advantage in the C3G market space.

• May 2024: Novartis presented results from the 6-month, double-blind period of the Phase III APPEAR-C3G study of FABHALTA (iptacopan) at the late-breaking clinical trials session of the European Renal Association (ERA) congress.

Pegcetacoplan (APL-2): Apellis Pharmaceuticals

Apellis’ Pegcetacoplan (APL-2) is an investigational, targeted C3 inhibitor designed to regulate excessive complement activation, which can lead to the onset and progression of many serious diseases. It is a15-amino acid cyclic peptide conjugated to each end of a linear polyethylene glycol molecule that binds to C3 and C3b, directly preventing activation of C3, C5, and the alternative pathway. Pegcetacoplan (marketed as Empaveli) is approved in the United States for the treatment of adults with paroxysmal nocturnal hemoglobinuria.

• May 2024: Apellis Pharmaceuticals and Sobi announced positive one-year results from the Phase II NOBLE study investigating systemic pegcetacoplan, a targeted C3 therapy, for the treatment of post-transplant recurrence of C3G and primary Immune Complex- Membranoproliferative Glomerulonephritis (IC-MPGN).

Drug Class Insights

Renin-angiotensin-aldosterone system inhibitors: Angiotensin receptor blocker (ARB) and angiotensin-converting enzyme (ACE) inhibitors both are used to treat hypertension in C3G. Combination use of RAAS inhibitors showed higher efficiency compared with monotherapy and was associated with a higher incidence of adverse events.

Immunosuppressants: Corticosteroids, calcineurin inhibitors, corticosteroids in combination with mycophenolate mofetil (MMF), and others are used for the treatment of C3G. Among all nonspecific immunosuppressive therapies, MMF-based treatment is promising compared with others concerning clinical remission and renal survival.

Complement inhibitors are the primary class in the emerging pipeline for C3G therapy. Complement inhibitors Pegcetacoplan and Iptacopan perform well in C3G in terms of safety and effectiveness.

Complement 3 Glomerulopathy Market Outlook

According to the National Kidney Foundation (NKF), C3G stands for complement 3 glomerulopathy. The “C3” refers to a blood protein that plays a key role in normal immunity and the development of this disease whereas the “G” is for glomerulopathy, meaning damage to the glomeruli in the kidney. In addition, C3G includes dense deposit disease (DDD) and C3 glomerulonephritis (C3GN), which represent the two different patterns of damage and inflammation in the glomeruli. In other words, the damage and inflammation in the kidney tissue in DDD look different from that in C3GN when seen under a microscope.

Since there are no approved therapies for C3G, the market is mainly dominated by the use of off-label prescription drugs. Treatments for C3G include immunosuppressants in combination with corticosteroids, Renin-angiotensin-aldosterone system Inhibitors (RAAS), and other supportive therapies (calcineurin inhibitors, anti-complement therapies with eculizumab).

However, the current emerging market of C3G possesses an intermediate pipeline. There are no emerging therapies in their phase III developmental stage; however, a few potential emerging players are investigating their product candidates in the late- and mid-phase of the developmental stage, namely, Apellis Pharmaceuticals (Pegcetacoplan), and Novartis Pharmaceuticals (Iptacopan).

• The market size of Complement 3 Glomerulopathy in the seven major markets is estimated to be ~USD 35 million in 2023.
• The United States accounts for the largest market size of C3G, in comparison to EU4, the UK, and Japan, i.e., ~73% of the 7MM.
• Among the EU4 and the UK, Germany had the highest market size in 2023, while Italy had the lowest market size for Complement 3 Glomerulopathy in 2023.
• The current emerging market of C3G possesses an intermediate pipeline. There are two emerging therapies in the Phase III developmental stage i.e., Novartis Pharmaceuticals (Iptacopan (LNP023)) and Apellis Pharmaceuticals (Pegcetacoplan).

Complement 3 Glomerulopathy Drugs Uptake

This section focuses on the uptake rate of potential drugs expected to be launched in the market during 2020-2034, which depends on the competitive landscape, safety, efficacy data, and order of entry. It is important to understand that the key players evaluating their novel therapies in the pivotal and confirmatory trials should remain vigilant when selecting appropriate comparators to stand the greatest chance of a positive opinion from regulatory bodies, leading to approval, smooth launch, and rapid uptake. Iptacopan is an oral small-molecule inhibitor of complement factor B with potential immunomodulatory activity. Novartis is planning to file the drug in 2024. The drug is expected to launch in the US in 2025. In terms of safety, Iptacopan is better than Pegcetacoplan.

Complement 3 Glomerulopathy Activities

The report provides insights into therapeutic candidates in Phase III and II. 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 C3G emerging therapies.

KOL Views

To keep up with the real-world scenario in current and emerging market trends, we take opinions from Key Industry leaders working in the domain through primary research to fill the data gaps and validate our secondary research. Industry Experts contacted for insights on the evolving treatment landscape, patient reliance on conventional therapies, patient’s therapy switching acceptability, and drug uptake along with challenges related to accessibility, including Medical/scientific writers, nephrologists, Consultant Nephrologists, and Honorary Associate Professor at University Hospitals of Leicester NHS Trust, and Others.

The analysts connected with 20+ KOLs to gather insights; however, interviews were conducted with 10+ KOLs in the 7MM. Their opinion helps understand and validate current and emerging therapy treatment patterns or Complement 3 Glomerulopathy market trends.

Qualitative Analysis

We perform Qualitative and market Intelligence analysis using various approaches, such as SWOT analysis and Analyst views. 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.

Market Access and Reimbursement

The report provides detailed insights on the country-wise accessibility and reimbursement scenarios, programs making accessibility easier and out-of-pocket costs more affordable, insights on patients insured under federal or state government prescription drug programs, etc. The main cost savings driver was the maintenance-year complement inhibitor drug cost reduction. After treatment initiation, the mean annual maintenance-year costs of ravulizumab were at least 10% lower than those of eculizumab. Eculizumab maintenance-year costs grew over the model’s time horizon, owing to a cumulative incidence of BTH events resulting in up-dosing and associated higher drug costs. The improved benefit was due to reduced treatment burden and improved outcomes. No evidence was found to determine whether prophylactic use of eculizumab is effective and safe for preventing the recurrence of C3 glomerulopathy after kidney transplantation. Unsurprisingly, given the challenges of performing studies in rare diseases, the evidence for using eculizumab to treat C3 glomerulopathy in people who had experienced a recurrence of the condition post-transplant is confined to 10 case reports. Eculizumab improved or stabilized signs of C3 glomerulopathy in seven cases. A partial response was seen in one case and ineffective in two cases. More evidence is needed to assess better the safety and efficacy of eculizumab in this heterogeneous condition and to determine which patients are most likely to respond to treatment.

Scope of the Report

• The report covers a segment of key events, an executive summary, and a descriptive overview of Complement 3 Glomerulopathy, 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 has 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 Complement 3 Glomerulopathy 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 shape and drive the 7MM Complement 3 Glomerulopathy market.

Complement 3 Glomerulopathy Report Insights

• Patient Population
• Therapeutic Approaches
• Complement 3 Glomerulopathy Pipeline Analysis
• Complement 3 Glomerulopathy Market Size and Trends
• Existing and future Market Opportunity

Report Key Strengths

• Eleven Years Forecast
• The 7MM Coverage
• Complement 3 Glomerulopathy Epidemiology Segmentation
• Key Cross Competition
• Conjoint analysis
• Drugs Uptake and Key Market Forecast Assumptions

Complement 3 Glomerulopathy Report Assessment

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

FAQs

• What is the historical and forecasted Complement 3 Glomerulopathy patient pool in the United States, EU4 (Germany, France, Italy, and Spain) the United Kingdom, and Japan?
• What was the Complement 3 Glomerulopathy total market size, the market size by therapies, market share (%) distribution in 2020, and what would it look like in 2034? What are the contributing factors for this growth?
• What are the advantages of complement inhibitors over immunosuppressants?
• What will be the impact on market size after the launch of pegcetacoplan and iptacopan in C3G?
• 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?
• Patient acceptability in terms of preferred treatment options as per real-world scenarios?
• Which complement inhibitor generated the highest revenue by 2034?

Reasons to Buy

• The report will help develop business strategies by understanding the latest trends and changing treatment dynamics driving the Complement 3 Glomerulopathy 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 opportunities 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.
• Identifying strong upcoming players in the market will help devise strategies to help get ahead of competitors.
• 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 needs of the existing market so that the upcoming players can strengthen their development and launch strategy.