Atypical Hemolytic Uremic Syndrome (aHUS) - Market Insight, Epidemiology and Market Forecast - 2032

Key Highlights

• Atypical hemolytic uremic syndrome (aHUS) is a disease that causes abnormal blood clots to form in small blood vessels in the kidneys. These clots can cause serious medical problems if they restrict or block blood flow, including hemolytic anemia, thrombocytopenia, and kidney failure.
• The most common symptoms of aHUS are confusion, stroke, seizure, heart attack, high blood pressure, formation of blood clots in the kidney, heart, or other organs, nausea and vomiting, abdominal pain, and kidney damage.
• The diagnostic test of aHUS includes a complete blood count (CBC) test, which is used to measure the red blood cell and platelet count, and a blood test to check kidney function. Kidney health can be measured by a test called eGFR which is calculated using the creatinine level, age, sex, and race.
• In 2022, diagnosed cases of aHUS in the 7MM were nearly 4,800 cases.
• In the 7MM, more cases of aHUS in adolescents and adults than in pediatric patients. There were approximately 4,000 and 700 cases of adolescent adults and pediatric patients, respectively, in 2022.
• Therapy of aHUS is supportive, with attention to the management of acute kidney injury and systemic complications. Renal replacement therapy is required in patients with uremia, fluid overload, or electrolyte abnormalities. Plasma exchange and eculizumab, a complement inhibitor, offer specific forms of therapy. Currently, only two drugs have been approved for the treatment of aHUS, eculizumab, and ravulizumab.
• The United States accounted for the highest market size among the 7MM in 2022, expected to increase by 2032 with a CAGR of approximately 4% during the study period (2019-2032).
• Premium pricing of the drugs has resulted in the low commercial uptake of the drug, safety concerns with the treatment of aHUS, lack of definitive diagnostic criteria, and upcoming generic competition are expected to hit the aHUS disease market.

Report Summary

• The report offers extensive knowledge regarding the epidemiology segments and predictions, presenting a deep understanding of the potential future growth in diagnosis rates, disease progression, and treatment guidelines. It provides comprehensive insights into these aspects, enabling a thorough assessment of the subject matter.
• Additionally, an all-inclusive account of the current management techniques and emerging therapies and the elaborative profiles of late-stage (Phase III) and prominent therapies that would impact the current treatment landscape and result in an overall market shift has been provided in the report.
• The report also encompasses a comprehensive analysis of the aHUS market, providing an in-depth examination of its historical and projected market size (2019-2032). It also includes the market share of therapies, detailed assumptions, and the underlying rationale for our methodology. The report also includes drug outreach coverage in the 7MM region.
• The report includes qualitative insights that provide an edge while developing business strategies by understanding trends through SWOT analysis and expert insights/KOL views, including experts from various hospitals and prominent universities, patient journey, and treatment preferences that help shape and drive the 7MM aHUS market.

Market
Various key players are leading the treatment landscape of aHUS, such as Alexion Pharmaceuticals, Novartis, and Roche. The details of the country-wise and therapy-wise market size have been provided below.

• In 2022, the total market size of aHUS was around USD 1,300 million, which is expected to increase by 2032 during the study period (2019-2032) in the 7MM.
• In the total market size of aHUS in the 7MM, the United States accounted for the highest market size in 2022, followed by Germany and France.
• Among the emerging therapies, Novartis (iptacopan) and Roche (crovalimab) appear to be the drugs that can potentially transform the aHUS market.
• By 2032, among the emerging therapies, the highest revenue is expected to be generated by iptacopan, i.e., nearly USD 100 million in the EU4 and the UK.

aHUS Drug Chapters

The section dedicated to drugs in the aHUS report provides an in-depth evaluation of late-stage pipeline drugs (Phase III) related to aHUS.

The drug chapters section provides valuable information on various aspects related to clinical trials of aHUS, such as the pharmacological mechanisms of the drugs involved, designations, approval status, patent information, and a comprehensive analysis of the pros and cons associated with each drug. Furthermore, it presents the most recent news updates and press releases on drugs targeting aHUS.

Marketed Therapies

ULTOMIRIS (ravulizumab): Alexion Pharmaceuticals

ULTOMIRIS is a medication primarily indicated for the treatment of aHUS. Atypical hemolytic uremic syndrome is a rare and serious condition characterized by the formation of blood clots in small blood vessels throughout the body, leading to damage to vital organs, especially the kidneys. In September 2020, Alexion Pharmaceuticals announced that Japan's MHLW had approved ULTOMIRIS (ravulizumab) for adults and children living with aHUS.

Emerging Therapies

LNP023 (iptacopan): Novartis Pharmaceuticals

Iptacopan, also known as LNP023, is a first-in-class, orally-administered, small-molecule, potent, and highly selective factor B (FB) inhibitor, a key serine protease of the alternative pathway of the complement cascade. Currently, Iptacopan is in the Phase III development stage. The ongoing Phase III clinical trial is a multicenter, single-arm, open-label trial to evaluate the efficacy and safety of oral, twice-daily LNP023 in adult aHUS patients who are naive to complement inhibitor therapy and is expected to be completed by December 2024.

aHUS Market Outlook

The introduction of complement C5 inhibition into the treatment landscape has significantly improved patient prognosis and QoL. Currently available complement C5 inhibitors across the 7MM are SOLIRIS (eculizumab) and ULTOMIRIS (ravulizumab), both Alexion Pharmaceuticals products. Alexion Pharmaceuticals was acquired by AstraZeneca in 2021.

The treatment transition of patients being treated with eculizumab to ravulizumab has been established as a viable treatment strategy, as this would lead to a reduction in the dosing frequency, which would then lead to a significant reduction of economic burden (treatment-related costs of repeated infusions) and improve the overall QoL of patients.

Although eculizumab and ravulizumab are safe and effective, their high costs often limit their usage in the treatment landscape. Hence, efficacious pharmacologic options for managing the most prevalent and most disabling stages of aHUS are extremely limited; therefore, new treatments are desperately needed.

In a nutshell, a few potential therapies are being investigated to manage aHUS. Even though it is too soon to comment on the above-mentioned promising candidate to enter the market during the forecast period (2023-2032), it is safe to assume that the future of this market is bright. Eventually, these drugs shall create a significant difference in the landscape of aHUS in the coming years. The treatment space is expected to experience a significant positive shift in the coming years owing to the improvement in healthcare spending worldwide.

Further details are provided in the report.

aHUS Disease Understanding and Treatment

aHUS Overview

aHUS is an extremely rare disease characterized by low levels of circulating red blood cells due to their destruction (hemolytic anemia), low platelet count (thrombocytopenia) due to their consumption, and the inability of the kidneys to process waste products from the blood and excrete them into the urine (acute kidney failure), a condition known as uremia. It is a distinctly different illness from the more common disorder known as a typical hemolytic uremic syndrome, caused by E. coli-producing Shiga toxins (Stx HUS) and is generally foodborne.

Most cases of aHUS are genetic, although some may be acquired due to autoantibodies or for unknown reasons (idiopathic). aHUS may become chronic, and affected individuals may experience repeated episodes of the disorder.

There are two types of HUS: Typical HUS (caused by E. coli or other food/water-borne pathogens) and atypical HUS (usually a genetic mutation but sometimes triggered by other illnesses or unknown causes).

The signs and symptoms of aHUS result from the formation of tiny blood clots (microthrombi) in various small blood vessels. These clots reduce or prevent proper blood flow to various body organs, especially the kidneys. aHUS is a complex disorder, and multiple factors, including certain genetic, environmental, and immunologic factors, all play a role in its development.

aHUS Diagnosis

Diagnosing aHUS is complicated by the fact that it is more challenging to establish without a family history of the disorder. The diagnostic criteria associated with aHUS are hemolytic anemia (anemia in the presence of broken red blood cells), low platelet count (thrombocytopenia), and kidney dysfunction.

The diagnostic test of aHUS includes a complete blood count (CBC) test, which is used to measure the red blood cell and platelet count, and a blood test to check kidney function. Kidney health can be measured by a test called eGFR which is calculated using the creatinine level, age, sex, and race.

Specific testing is there; both HUS and aHUS share some signs and symptoms with another disease called thrombotic thrombocytopenic purpura (TTP), which has a different underlying cause. Doctors can measure levels of a certain protein in the blood, ADAMTS13, which may help clarify whether a patient has aHUS or TTP.

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

aHUS Treatment

Treatment of Atypical Hemolytic Uremic Syndrome is supportive, with attention to management of acute kidney injury and systemic complications. The use of packed cells is necessary in patients with severe anemia. Platelet transfusions are rarely required, except in counts are < 10 000/cu mm or thrombocytopenia associated with active bleeding or in patients undergoing invasive procedures.

Fluid and electrolyte management is important to maintain intravascular volume status and combat the consequences of aHUS, acute kidney injury, and multisystem organ failure. Electrolyte disturbances should be promptly corrected and nephrotoxic medications avoided. Hypertension should be managed with appropriate agents. Renal replacement therapy is required in patients with uremia, fluid overload, or electrolyte abnormalities. Plasma exchange and eculizumab or rivalizumab, a complement inhibitor, offer specific forms of therapy.

For years, plasma therapy was the standard treatment for individuals with aHUS. Both infusions of fresh frozen plasma (plasma infusion), as well as plasma exchange (plasmapheresis), were utilized. Fresh frozen plasma is a blood derivative that is obtained from donors. Plasma exchange removes potentially harmful substances (e.g., toxins, metabolic substances, and plasma parts) from the blood. Blood is removed from the affected individual, and blood cells are separated from the plasma. The plasma is then replaced with other human plasma, and the blood is transfused into the affected individuals. Plasma exchange can also remove mutant factors and autoantibodies.

Further details related to treatment and management are provided in the report.

aHUS Epidemiology

The aHUS epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by total prevalent cases, diagnosed cases, age-specific cases, and treated cases of aHUS in the United States, EU4 countries (Germany, France, Italy, Spain) and the United Kingdom, and Japan from 2019 to 2032.

• Among the 7MM, the United States accounted for the highest number of prevalent cases of aHUS in 2022, nearly 3,500 cases. These cases are anticipated to increase by 2032.
• In 2022, EU4 and the UK accounted for more cases of aHUS in adolescents and adults than in pediatric patients.
• Among EU4 and the UK, Germany accounted for the highest number of prevalent cases in 2022, while Spain accounted for the least.
• In 2022, the treated cases of aHUS in Japan were around 200 cases.

KOL Views

To stay abreast of the latest trends in the market, we conduct primary research by seeking the opinions of Key Opinion Leaders (KOLs) and Subject Matter Experts (SMEs) who work in the relevant field. This helps us fill any gaps in data and validate our secondary research.

The publisher reached out to industry experts to gather insights on various aspects of aHUS, including the evolving treatment landscape, patients' reliance on conventional therapies, their acceptance of therapy switching, drug uptake, and challenges related to accessibility. The experts we contacted included medical/scientific writers, professors, and researchers from prestigious universities in the US, Europe, the UK, and Japan.

The team of analyststs connected with more than 15 KOLs across the 7MM. We contacted institutions such as the University of Munich, the University of Tokyo, the European Dialysis and Transplant Association, the American Society of Nephrology, etc., among others. By obtaining the opinions of these experts, we gained a better understanding of the current and emerging treatment patterns in the aHUS market, which will assist our clients in analyzing the overall epidemiology and market scenario.

Qualitative Analysis

The publisher performs 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, designation, 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 trials for aHUS, one of the most important primary endpoints was achieving hemolysis control, LDH normalization, etc. Based on these, the overall efficacy is evaluated.

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

Because newly authorized drugs are often expensive, some patients escape receiving proper treatment or use off-label, less expensive prescriptions. Reimbursement plays a critical role in how innovative treatments can enter the market. The cost of the medicine, compared to the benefit it provides to patients who are being treated, sometimes determines whether or not it will be reimbursed. Regulatory status, target population size, the setting of treatment, unmet needs, the number of incremental benefit claims, and prices can all affect market access and reimbursement possibilities.

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.

aHUS Report Insights

• Patient Population
• Therapeutic Approaches
• aHUS Market Size and Trends
• Existing Market Opportunity

aHUS Report Key Strengths

• Ten-year Forecast
• The 7MM Coverage
• aHUS Epidemiology Segmentation
• Key Cross Competition

aHUS Report Assessment

• Current Treatment Practices
• Reimbursements
• Market Attractiveness
• Qualitative Analysis (SWOT, Conjoint Analysis, Unmet needs)

Key Questions Answered

• Would there be any changes observed in the current treatment approach?
• Will there be any improvements in aHUS management recommendations?
• Would research and development advances pave the way for future tests and therapies for aHUS?
• Would the diagnostic testing space experience a significant impact and lead to a positive shift in the treatment landscape of aHUS?
• What kind of uptake will the new therapies witness in coming years in aHUS patients?