Homocystinuria Market New
DelveInsight’s ‘Homocystinuria (HCU) - Market Insights, Epidemiology, and Market Forecast—2030’ report delivers an in-depth understanding of the HCU, historical and forecasted epidemiology as well as the HCU market trends in the United States, EU5 (Germany, France, Italy, Spain, and United Kingdom), and Japan.
The HCU market report provides current treatment practices, emerging drugs, HCU market share of the individual therapies, current and forecasted HCU market size from 2017 to 2030 segmented by seven major markets. The Report also covers current HCU treatment practice/algorithm, market drivers, market barriers, and unmet medical needs to curate the best of the opportunities and assesses the underlying potential of the market.
• The United States
• EU5 (Germany, France, Italy, Spain, and the United Kingdom)
Study Period: 2017–2030
Homocystinuria (HCU): Disease Understanding and Treatment Algorithm
HCU is an autosomal recessive inherited disorder of amino acid metabolism causing elevated plasma concentrations of homocysteine and its metabolites (homocysteine, homocysteine-cysteine complex), buildup in blood and urine. This buildup occurs when the body cannot properly process homocysteine or methionine, another amino acid. High levels of homocysteine and abnormal levels of methionine can cause many different symptoms in the body and lead to serious, lifelong health problems.
The cause of the buildup of homocysteine varies depending on the genetic disorder. Mutations in the CBS gene cause the most common form of HCU. Rarely, HCU can be caused by mutations in several other genes. The enzymes made by the MTHFR, MTR, MTRR, and MMADHC genes play roles in converting homocysteine to methionine. Among the different forms of HCU depending on the genetic disorder, the most common are HCU due to CBS deficiency, HCU due to cobalamin cofactor metabolism (cbl) defect, and HCU due to Methylenetetrahydrofolate Reductase (MTHFR) deficiency.
Symptoms associated with HCU vary depending on the severity of the case. The developmental delays, failure to thrive, and poor vision are some of the first signs that the condition is present and often it leads to the diagnosis of the disease. Other signs and symptoms may include abnormally long limbs, chest deformities, a high arch on the foot, mental disorders, and an abnormal curvature of the spine. The most common form of HCU is characterized by nearsightedness (myopia), dislocation of the lens at the front of the eye, an increased risk of abnormal blood clotting, and brittle bones prone to fracture. Infants born with the disease often appear healthy at first, as symptoms are not obvious. As the patient reaches around the age of three years old, signs and symptoms begin to become more noticeable.
Homocystinuria (HCU) Diagnosis
Initial screening for HCU involves newborn screening to identify conditions that can affect a child’s long-term health or survival. Newborn screening for HCU specifically tests for methionine levels. Most children diagnosed through newborn screening have the pyridoxine-unresponsive form of HCU due to CBS deficiency. In affected patients, the presence of homocysteine in the urine is a consistent finding, especially after early infancy. CBS enzyme activity can be measured in many tissues, including fibroblasts, lymphocytes, liver, amniocytes, and chorionic villi (biopsy or cultured cells).
Blood plasma samples are usually tested for the presence of high homocysteine levels. The total homocysteine (tHcy) concentration is measured. A high amount of certain amino acids (homocysteine and methionine) in the blood and a high amount of homocysteine in the urine might indicate that they have HCU. The diagnosis may then be confirmed by genetic testing of the CBS gene and/or measurement of CBS enzyme activity in cultured fibroblasts.
The diagnosis of HCU is mainly done by Liver Enzyme Assay to check the level of liver enzymes in the blood, a homocysteine test measures the amount of homocysteine present in a person's blood, Imaging tests (Skeletal X-rays), Skin biopsy and Ophthalmic Exam. The doctor may also recommend a liver biopsy. The tissue is then analyzed in a laboratory to help doctors diagnose a variety of disorders. For the diagnosis of HCU in a person, the extracted tissue is used in an enzyme assay to check the enzyme activity.
Currently, there is no cure for this disorder. The treatment of HCU is directed toward preventing or reducing the symptoms commonly associated with the disorder by controlling the levels of homocysteine in the fluid portion of the blood (plasma). Treatment may include therapy with pyridoxine (vitamin B6), a diet that restricts the intake of protein and methionine, betaine therapy, and supplementation with folate (vitamin B9) or cobalamin (vitamin B12).
Pyridoxine is considered as the first-line treatment of HCU as in some patients, it is possible to control the levels of homocysteine with high doses of vitamin B6 (pyridoxine). Folate and vitamin B12supplementation optimize the conversion of homocysteine to methionine by methionine synthase, thus helping to decrease the plasma homocysteine concentration.
Dietary treatment for B6-non-responsive neonates requires a methionine-restricted diet with frequent metabolic monitoring. Dietary treatment is considered for clinically diagnosed individuals but often is not tolerated if begun in mid-childhood or later.
Cystadane (Betaine anhydrous for oral solution) is the first agent approved by the US FDA for the treatment of HCU involving CBS, MTHFR, or cbl defects. It is considered as adjunctive therapy in patients with abnormal levels of homocysteine.
The HCU epidemiology division provides insights about historical and current HCU patient pool and forecasted trends for every seven major countries. It helps to recognize the causes of current and forecasted trends by exploring numerous studies and views of key opinion leaders. This part of the DelveInsight report also provides the diagnosed patient pool and their trends along with assumptions undertaken.
In the year 2017, the total prevalent case of HCU was 41,684 cases in the 7MM which are expected to grow during the study period, i.e., 2017–2030.
The disease epidemiology covered in the report provides historical as well as forecasted HCU epidemiology [segmented as Total Prevalent Cases of HCU, Total Diagnosed Cases of HCU, Gender-specific Prevalent cases of HCU, Age-specific Prevalent Cases of HCU, and Treated cases of HCU] in the 7MM covering the United States, EU5 countries (Germany, France, Italy, Spain, and the United Kingdom), and Japan from 2017 to 2030.
Country Wise- HCU Epidemiology
Estimates show that the highest cases of HCU in the 7MM were in the United States, followed by Germany, France, the United Kingdom, Italy, Spain, and Japan in 2017.
• In the United States, the total number of prevalent cases of HCU was 32,515 cases in the year 2017 which are expected to grow during the study period, i.e., 2017–2030.
• In the year 2017, the total prevalent cases of HCU were 8,537 cases in EU-5 which are expected to grow during the study period, i.e., 2017–2030.
• In Japan, the total number of prevalent cases of HCU was 632 cases in the year 2017 which are expected to grow during the study period, i.e., 2017–2030.
HCU Drug Chapters
The drug chapter segment of the HCU report encloses the detailed analysis of HCU marketed drugs and late stage (Phase-III and Phase-II) pipeline drugs. It also helps to understand the HCU 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.
HCU Approved Drugs
Cystadane/Betaine anhydrous (Recordati Rare Diseases Inc.)
Cystadane (Betaine anhydrous) is a methylating agent approved for the treatment of homocystinuria involving CBS, MTHFR, or cbl defects. Betaine anhydrous acts as a methyl donor for remethylation of homocysteine to methionine, increasing the plasma and tissue concentrations of methionine while reducing homocysteine levels. One of the aims of betaine anhydrous treatment is to keep plasma total homocysteine levels as low as possible. As per the current guidelines, additional treatment such as betaine should be considered in CBS-deficient B6 responders in whom total homocysteine levels remain above 50 μmol/L. Cystadane is usually prescribed along with other therapies. Individual treatment will be based on the cause of homocystinuria – CBS deficiency (classical homocystinuria), MTHFR deficiency, or cbl defect – and other factors.
In October 1996, the US Food and Drug Administration (FDA) approved Cystadane (active ingredient- Betaine) for the treatment of HCU to decrease elevated homocysteine blood levels. In February 2007, European Commission (EC) granted marketing authorization for Cystadane (Betaine anhydrous), valid throughout the European Union and in January 2014, Japan granted the manufacturing and marketing approval of Cystadane for the treatment of the indication HCU.
Note: Detailed Current therapies assessment will be provided in the full report of HCU
HCU Emerging Drugs
OT-58 (Orphan technologies)
OT-58 is being developed in clinical studies for patients suffering from the rare disease classical HCU. OT-58 is designed to help patients reduce their homocysteine levels, improve patient health, and restore a normal lifestyle. Reduced CBS activity results in the inability to metabolize, or process, homocysteine. This can lead to dangerous elevations of homocysteine and symptoms. OT-58 is a modified enzyme therapy that may dramatically decrease tissue and plasma levels of homocysteine, and as a result may prevent, delay, and reverse clinical abnormalities, and reduce dietary restrictions in HCU, and other diseases that exhibit elevated homocysteine values.
In March 2020 OT-58 has been designated a rare pediatric disease (RPD) by the US FDA. Previously, in the same year, 0T-58 was also been granted by both, Fast Track Designation and Orphan Drug Designation by FDA for the treatment of HCU caused by CBS deficiency.
ACN00177/Homocystinase (Aeglea BioTherapeutics)
ACN00177 (Homocystinase) is the clinical candidate being developed as an engineered human enzyme designed to treat HCU. It is anticipated that the enzyme therapy with ACN00177 may degrade homocysteine and the oxidized form homocysteine in the blood. A significant reduction of homocysteine/homocysteine levels may halt or slow the progression of the disease in the patients. ACN00177 has been designed as a novel recombinant human enzyme, which degrades the amino acid homocysteine and its related homocysteine dimer. With this mechanism, ACN00177 is intended to lower the abnormally high blood levels of homocysteine to the normal range in patients with HCU
Note: Detailed emerging therapies assessment will be provided in the final report.
HCU Market Outlook
HCU is a rare metabolic condition that is characterized by an accumulation of the amino acid homocysteine in the serum and increased excretion of homocysteine in the urine. The treatment of HCU is directed toward preventing or reducing the symptoms commonly associated with the disorder by controlling the levels of homocysteine in the fluid portion of the blood (plasma). Current treatment strategies in the US aims to lower homocysteine concentrations in the blood to a normal range. Cystadane (Betaine anhydrous) is a prescription drug approved by the US FDA in October 1996 for the treatment of pediatric and adult patients with HCU. Cystadane (Betaine anhydrous for oral solution) is the first agent approved by the US FDA to treat HCU involving CBS, MTHFR, or cbl defects. The strategies in Japan for the treatment of HCU in CBS deficiency include dietary supplementation with betaine (Bet) and cysteine, as well as reducing the load on the affected pathway with a low methionine (Met) diet.
The other treatment options may include therapy with pyridoxine (vitamin B6), a diet that restricts the intake of protein and methionine, and supplementation with folate (vitamin B9) or cobalamin (vitamin B12). Specific symptoms of HCU are treated as appropriate. For example, dislocation of the eyes' lenses (ectopia lentis) or certain skeletal malformations may be treated surgically.
At present, some companies have indulged themselves in initiating clinical trials that investigate new treatment options for how to use existing treatment options better. Current ongoing trials are evaluating enzyme-based therapies that may dramatically decrease tissue and plasma levels of homocysteine, and as a result, may prevent, delay, and reverse clinical abnormalities, and reduce dietary restrictions in homocystinuria and other diseases that exhibit elevated homocysteine values. Key players such as Orphan Technologies (OT-58) and Aeglea BioTherapeutics (ACN00177) are investigating their candidates in the early stages of clinical development.
The HCU market size in the 7MM is expected to change during the study period 2017–2030. The therapeutic market of HCU in the seven major markets was USD 7.2 million in 2017 which is expected to increase during the study period (2017–2030). According to the estimates, the highest market size of HCU is found in the United States followed by Germany.
The United States Market Outlook
In 2017, the total market size of HCU therapies was USD 6.5 million in the United States which is expected to increase in the study period (2017–2030).
EU-5 Countries: Market Outlook
In 2017, the total market size of HCU therapies was USD 0.7 million in the EU-5 countries which is expected to increase in the study period (2017–2030).
Japan Market Outlook
The total market size of HCU therapies in Japan was USD 0.1 million in 2017 which is expected to increase in the study period (2017–2030).
HCU Pipeline Development Activities
The drugs which are in pipeline include:
• OT-58 (Orphan technologies)
• ACN00177/Homocystinase (Aeglea BioTherapeutics)
Note: Detailed emerging therapies assessment will be provided in the final report.
HCU Drugs Uptake
Pyridoxine is effective in around 50% of the patients due to CBS deficiency and assuming the role of emerging therapies on approval will be mainly around the remaining 50% of the patients who are not responding to pyridoxine.
Access and Reimbursement Scenario in HCU Therapies
• Cystadane has been designated an orphan medicine. The US Company Recordati Rare Diseases Inc. has developed two separate programs to assist patients eligible for financial support for their products: the Patient Assistance Program (PAP), valid for all products, and the Co-Pay Assistance Program (CAP). Co-Pay Assistance Program (CAP) provides financial support to insured patients, for all or part of their financial responsibilities, for certain Recordati Rare Diseases Inc products up to a predefined maximum limit. Patient assistance programs (PAPs) provide medication assistance for uninsured or under-insured patients, those who cannot afford them, and patients with private insurance coverage who have exhausted their lifetime limit because of the high cost of orphan drugs.
• As there is a lack of approved therapies for the treatment of HCU, there are no reimbursement policies available. For example, betaine anhydrous for the treatment of homocystinuria was approved by the EMEA based on the data from a review article showing biochemical efficacy and related improvements regarding the disease symptoms of betaine related to historical data of untreated patients.
To keep up with current market trends, we take KOLs and SME’s opinion working in the HCU domain through primary research to fill the data gaps and validate our secondary research. Their opinion helps to understand and validate current and emerging therapies treatment patterns or HCU market trends. This will support the clients in potential upcoming novel treatment by identifying the overall scenario of the market and the unmet needs.
Competitive Intelligence Analysis
We perform Competitive and Market Intelligence analysis of the HCU Market by using various Competitive Intelligence tools that includes – SWOT analysis, PESTLE analysis, Porter’s five forces, BCG Matrix, Market entry strategies, etc. The inclusion of the analysis entirely depends upon the data availability.
Scope of the Report
• The report covers the descriptive overview of HCU, explaining its causes, signs and symptoms, pathophysiology, and currently available therapies.
• Comprehensive insight has been provided into the HCU epidemiology and treatment in the 7MM.
• Additionally, an all-inclusive account of both the current and emerging therapies for HCU is provided, along with the assessment of new therapies, which will have an impact on the current treatment landscape.
• A detailed review of the HCU market; historical and forecasted is included in the report, covering drug outreach in the 7MM.
• The report provides an edge while developing business strategies, by understanding trends shaping and driving the global HCU market.
• In the coming years, the HCU market is set to change due to the rising awareness of the disease and incremental healthcare spending across the world; which would expand the size of the market to enable the drug manufacturers to penetrate more into the market.
• The companies and academics are working to assess challenges and seek opportunities that could influence HCU R&D. The therapies under development are focused on novel approaches to treat/improve the disease condition.
• Major players are involved in developing therapies for HCU. The launch of emerging therapies will significantly impact the HCU market.
• A better understanding of disease pathogenesis will also contribute to the development of novel therapeutics for HCU.
• Our in-depth analysis of the pipeline assets across different stages of development (Phase III and Phase II), different emerging trends, and comparative analysis of pipeline products with detailed clinical profiles, key cross-competition, launch date along with product development activities will support the clients in the decision-making process regarding their therapeutic portfolio by identifying the overall scenario of the research and development activities.
HCU Report Insights
• Patient Population
• Therapeutic Approaches
• HCU Pipeline Analysis
• HCU Market Size and Trends
• Market Opportunities
• Impact of upcoming Therapies
HCU Report Key Strengths
• 11 Years Forecast
• 7MM Coverage
• HCU Epidemiology Segmentation
• Key Cross Competition
• Highly Analyzed Market
• Drugs Uptake
HCU Report Assessment
• SWOT Analysis
• Current Treatment Practices
• Unmet Needs
• Pipeline Product Profiles
• Conjoint Analysis
• Market Attractiveness
• Market Drivers and Barriers
• What was the HCU Market share (%) distribution in 2017 and how it would look like in 2030?
• What would be the HCU total market size as well as market size by therapies across the 7MM during the study period (2017–2030)?
• What are the key findings of the market across the 7MM and which country will have the largest HCU market size during the study period (2017–2030)?
• At what CAGR, the HCU market is expected to grow in the 7MM during the study period (2017–2030)?
• What would be the HCU market outlook across the 7MM during the study period (2017–2030)?
• What would be the HCU market growth till 2030 and what will be the resultant market size in the year 2030?
• How would the market drivers, barriers, and future opportunities affect the market dynamics and subsequent analysis of the associated trends?
• HCU patient types/pool where unmet need is more and whether emerging therapies will be able to address the residual unmet need?
• How emerging therapies are performing on the parameters like efficacy, safety, route of administration (RoA), treatment duration, and frequencies based on their clinical trial results?
• Among the emerging therapies, what are the potential therapies which are expected to disrupt the HCU market?
• What are the disease risks, burdens, and unmet needs of the HCU?
• What is the historical HCU patient pool in the seven major markets covering the United States, EU5 (Germany, France, Italy, Spain, and the United Kingdom), and Japan?
• What would be the forecasted patient pool of HCU in the 7 major markets covering the United States, EU5 (Germany, France, Italy, Spain, and the United Kingdom), and Japan?
• What will be the growth opportunities in the 7MM concerning the patient population about HCU?
• Out of all the 7MM countries, which country would have the highest prevalent population of HCU during the study period (2017–2030)?
• At what CAGR the population is expected to grow in the 7MM during the study period (2017–2030)?
• What are the various recent and upcoming events which are expected to improve the diagnosis of HCU?
Current Treatment Scenario and Emerging Therapies:
• What are the current options for the treatment of HCU?
• What are the current treatment guidelines for the treatment of HCU in the US, Europe, and Japan?
• How many companies are developing therapies for the treatment of HCU?
• How many therapies are developed by each company for the treatment of HCU?
• How many emerging therapies are in the mid-stage and late stages of development for the treatment of HCU?
• What are the key collaborations (Industry–Industry, Industry-Academia), Mergers and acquisitions, licensing activities related to the HCU therapies?
• What are the recent novel therapies, targets, mechanisms of action, and technologies developed to overcome the limitation of existing therapies?
• What are the clinical studies going on for HCU and their status?
• What are the key designations that have been granted for the emerging therapies for HCU?
• What is the global historical and forecasted market of HCU?
Reasons to buy
• The report will help in developing business strategies by understanding trends shaping and driving the HCU market.
• To understand the future market competition in the HCU market and Insightful review of the key market drivers and barriers.
• Organize sales and marketing efforts by identifying the best opportunities for HCU in the US, Europe (Germany, France, Italy, Spain, and 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.
• Organize sales and marketing efforts by identifying the best opportunities for the HCU market.
• To understand the future market competition in the HCU market.