Congenital Hyperinsulinism - Market Insights, Epidemiology and Market Forecast- 2030
発行: DelveInsight Business Research LLP
ページ情報: 英文 166 Pages
DelveInsight's 'Congenital Hyperinsulinism (CHI) - Market Insights, Epidemiology and Market Forecast- 2030' report delivers an in-depth understanding of the Congenital Hyperinsulinism (CHI), historical and forecasted epidemiology as well as the Congenital Hyperinsulinism (CHI) market trends in the United States, EU5 (Germany, Spain, Italy, France, and United Kingdom) and Japan.
The Congenital Hyperinsulinism (CHI) market report provides current treatment practices, emerging drugs, and market share of the individual therapies, current and forecasted 7MM Congenital Hyperinsulinism (CHI) market size from 2017 to 2030. The report also covers current Congenital Hyperinsulinism (CHI) 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.
Study Period: 2017-2030
Congenital Hyperinsulinism (CHI) Overview
Congenital hyperinsulinism (CHI) refers to a clinically, genetically, and morphologically heterogeneous group of disorders associated with dysregulated insulin secretion. This condition causes individuals to have abnormally high levels of insulin, which is a hormone that helps control blood sugar levels. People with this condition have frequent occurrences of low blood sugar (hypoglycemia). These occurrences can lead to a lack of energy (lethargy), irritability, or difficulty feeding in infants and young children. Repeated episodes of low blood sugar increase the risk of severe complications such as breathing difficulties, seizures, intellectual disability, vision loss, brain damage, and coma. CHI affects approximately 1 in 50,000 newborns, and is more common in certain populations, affecting up to 1 in 2,500 newborns.
Genetic forms of CHI are due to mutation in the genes involved in the regulation of insulin secretion. CHI typically presents with fasting hypoglycemia but can present with postprandial hypoglycemia or, in some cases, hypoglycemia can be provoked by protein/leucine loading or even exercise. Patients with CHI can vary in their presentation from having no symptoms to having severe, medically unresponsive disease, which might require a near-total pancreatectomy.
Mutations in the ABCC8 and KCNJ11 genes are the most common causes of CHI and account for 40-45% of all cases (82% of diazoxide-unresponsive patients), whereas mutations have been identified on six other genes in approximately 5-10% of the cases. The genetic etiology for the remaining 45-55% of patients is still unknown. 55-60% of diazoxide-unresponsive CHI are focal forms, whereas 40-45% are diffuse forms, in western countries.
Histologically, CHI has been classified into two major subgroups: diffuse (affecting the whole pancreas) and focal (being localized to a single region of the pancreas) disease. Advances in molecular genetics, radiological imaging techniques (such as fluorine-18 L-3, 4-dihydroxyphenylalanine-PET-CT (18FDOPA-PET-CT scanning), and surgical techniques have completely changed the clinical approach to infants with severe congenital forms of hyperinsulinemic hypoglycemia.
Congenital Hyperinsulinism (CHI) Diagnosis
The main criterion of CHI is inadequate insulin secretion, which may be diagnostic if insulin levels are increased, normal or detectable in the presence of hypoglycemia (<2.5 mmol/L). There is no correlation between the severity of hypoglycemia and serum insulin levels. One of the other criteria is intravenous glucose requirement higher than 8-10 mg/kg/min to maintain normoglycemia. A good glycemic response to glucagon injection is also indicative of CHI. A 4-6 h fasting test can help diagnose CHI if insulin concentration is not abnormal in the presence of hypoglycemia. Some forms of CHI may portray elevated serum lactate levels may also be found. Increased serum ammonia concentration during hypoglycemia may be associated with hyperinsulinism/ hyperammonemia syndrome. The molecular genetic analysis for SUR1 and KIR6.2 genes mutations may confirm the diagnosis of CHI. Another indicator of excess insulin is a glucagon stimulation test. Glucagon is a hormone that opposes insulin action and stimulates the release of glucose from liver glycogen stores. A rise in blood glucose after glucagon administration at the time of hypoglycemia is a sensitive marker for hyperinsulinism.
The diagnostic criteria for CHI include:
A major specific but inconstant diagnostic criterion is the glucose infusion rate required to maintain blood glucose above 3 mmol/L. A glucose infusion rate higher than 10 mg/kg.min in a neonate proves insulin-related hypoglycemia.
Congenital Hyperinsulinism (CHI) Treatment
Prompt treatment of hypoglycemia due to HI is crucial to avoid brain damage. Other alternative fuels, such as ketones or lactate, may be available for the brain during periods of hypoglycemia. In contrast, HI prevents the production of these fuels and leaves the brain without a source of energy. Hypoglycemia can be treated by giving a carbohydrate-containing drink by mouth or, if severe, by giving glucose through the vein or by injecting glucagon.
Medications used to treat HI include diazoxide, octreotide, and glucagon. Emergency management includes parenteral glucose infusion, glucagon administration and frequent feeding. An individualized long-term management plan for each patient aims to normalize plasma glucose levels, provide an age-adjusted fasting tolerance, and avoid neurological symptoms associated with hypoglycemia. The introduction of pharmacological therapy should be one at a time to gauge the response and to monitor their side effects carefully.
Approximately 95-99% of children with diffuse KATP-HI require pancreatectomies. The surgeries are not mandatorily curative, and the patients may continue to require frequent feeds and medications to prevent hypoglycemia post-surgery. The hope with such surgery is to minimize the intense medical regimen that otherwise would be needed to protect the child from recurrent, severe hypoglycemia.
Currently, the first-line treatment of CHI involves the use of KATP channel agonist (diazoxide) alone or in combination with glucagon. The second-line treatment option for diazoxide unresponsive patients includes somatostatin analogs (octreotide), glucagon, calcium channel antagonists (nifedipine), and others (glucocorticosteroids and alpha-glucosidase).
The disease epidemiology covered in the report provides historical as well as forecasted epidemiology segmented by Total Diagnosed Prevalent Population of Congenital Hyperinsulinism (CHI), Type-specific Diagnosed Prevalence based on Cause of Congenital Hyperinsulinism (CHI), Type-specific Diagnosed Prevalence based on Histological Presentation of Congenital Hyperinsulinism (CHI) and Mutation-specific Diagnosed Prevalence of Congenital Hyperinsulinism (CHI) in the 7MM market covering the United States, EU5 countries (Germany, France, Italy, Spain, and United Kingdom) and Japan from 2017 to 2030.
This section provides glimpse of the Congenital Hyperinsulinism (CHI) epidemiology in the 7MM.
The epidemiology segment also provides the Congenital Hyperinsulinism (CHI) epidemiology data and findings across the United States, EU5 (Germany, France, Italy, Spain, and the United Kingdom) and Japan.
The drug chapter segment of the Congenital Hyperinsulinism (CHI) report encloses the detailed analysis of Congenital Hyperinsulinism (CHI) marketed drugs and mid and late stage pipeline drugs. It also helps to understand the Congenital Hyperinsulinism (CHI) clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details of each included drug and the latest news and press releases.
Congenital Hyperinsulinism (CHI) Marketed Drugs
Proglycem: Teva Pharmaceuticals
Proglycem (diazoxide) is a nondiuretic benzothiadiazine derivative taken orally for the management of symptomatic hypoglycemia, which is used to treat low blood sugar levels due to certain medical conditions that cause the release of too much insulin from the pancreas. It works mainly by blocking the pancreas from releasing insulin; this action helps to increase blood sugar. As per the information available from the FDA, the oral capsules of Proglycem have been discontinued. In contrast, the oral suspension is clinically prescribed and currently underuse.
Product details in the report…
Congenital Hyperinsulinism (CHI) Emerging Drugs
Dasiglucagon: Zealand Pharma
Zealand Pharma is developing dasiglucagon (ZP4207), a potential first-in-class glucagon analog with a unique stability profile in a liquid formulation; glucagon is the physiological counter regulator of insulin, causing a rise in blood glucose. The drug is stable in an aqueous formulation, suitable for pump use, and, therefore, for treatment of CHI. Dasiglucagon (ZP4207) is being evaluated in phase III for congenital hyperinsulinism. The company also intends to evaluate the potential of chronic dasiglucagon infusions delivered through a pump to prevent hypoglycemia in children diagnosed with CHI in the phase III clinical trial. Moreover, researchers hope to reduce morbidities associated with hypoglycemia, neurodevelopmental defects, and the need for pancreatectomy.
Product details in the report…
XOMA 358/RZ358: XOMA/Rezolute
RZ358 is an intravenously administered human monoclonal antibody that binds with high potency and selectivity to an allosteric site on the insulin receptor. It counteracts the effects of elevated insulin at its target tissues by diminishing the binding and downstream signaling of insulin at its receptor. This unique mechanism of action gives properties of reversibility and graded activity, which are dependent on the extent of insulin elevation. Therefore, RZ358 is ideally suited as a potential therapy for hyperinsulinism, and it is being developed to treat the hypoglycemia associated with diseases such as CHI. The drug is a first-in-class fully human antibody that inhibits the effects of elevated insulin (hyperinsulinemia) via allosteric modulation of the insulin receptor. XOMA 358's novel mechanism of action makes it well-suited as a therapy for severe, persistent hypoglycemia caused by hyperinsulinemic conditions, such as CHI. Previously, XOMA completed a phase II developmental trial of the drug in patients with CHI and patients with hypoglycemia post-bariatric surgery (PBS). In December 2017, Rezolute, formerly known as AntriaBio, acquired an exclusive global license to develop and commercialize XOMA 358 (now RZ358) for all indications. In July 2020, the company announced Resumption and US-Expansion of its phase IIb RIZE study (RZ358-606) in CHI.
Product details in the report…
CSI-Glucagon (Continuous Subcutaneous Glucagon Infusion): Xeris Pharmaceuticals
Xeris Pharmaceuticals is developing CSI-Glucagon (continuous subcutaneous glucagon infusion) for the prevention of hypoglycemia in patients with congenital hyperinsulinism. Xeris proprietary glucagon formulation has the potential to provide the first soluble, room temperature stable, pump-delivered glucagon product for continuous infusion to combat high insulin levels and thus prevent severe hypoglycemia. The company utilizes proprietary XeriSol and XeriJect non-aqueous formulation technology platforms designed to address the challenges presented by aqueous formulations of certain drugs. The drug has already completed phase II trial for the prevention of hypoglycemia in patients with CHI in October 2018.
Product details in the report…
Avexitide: Eiger BioPharmaceuticals
Avexitide (formerly known as Exendin 9-39) is a 31 amino acid peptide fragment of exenatide under development by Eiger BioPharmaceuticals for the treatment of CHI. It is a well-characterized, competitive GLP-1 antagonist that blocks GLP-1 from binding to the GLP-1 receptor, reduces insulin secretion, and prevents steep falls in glucose levels (EigerBio). In November 2015, Eiger BioPharmaceuticals acquired an exclusive license to avexitide from Stanford University for the treatment of post-bariatric surgical hypoglycemia. The drug is currently in phase II of clinical trials for CHI, and the company is assessing strategic options to advance the drug in PBH and CHI.
Product details in the report…
As per the Congenital Hyperinsulinism International, congenital hyperinsulinism (HI) is the most frequent cause of severe, persistent hypoglycemia in newborn babies and children. In most of the countries, it is estimated to occur in approximately 1/25,000-1/50,000 births. Out of which, about 60% of babies with HI develop hypoglycemia during the first month of life, while 30% might be diagnosed in a later stage of their life. Thus, initiation of early treatment is essential for aggressive prevention of hypoglycemia and resulting brain damage.
There is only one approved therapy for CHI in the market, namely, Proglycem (diazoxide)-a non-diuretic benzothiadiazine derivative used for the management of symptomatic hypoglycemia. Proglycem capsules and suspension are manufactured by IVAX Pharmaceuticals and Teva Pharmaceuticals, respectively; the suspension was manufactured for Gate Pharmaceuticals, a division of Teva Pharmaceuticals. As per the FDA, the oral capsules have been discontinued; however, the oral suspension is clinically prescribed and currently underuse. Additionally, several generic versions of this drug is also available in the market now.
Parenteral glucose infusion is administered intravenously as a bolus as it is a potent trigger for insulin secretion. Glucagon administration is used as first-line therapy for managing CHI patients, particularly in emergencies where patients are unable to take oral feed and/or intravenous access is difficult to obtain. Frequent feeding with high-calorie carbohydrates can reduce the frequency and severity of hypoglycemic episodes; hence, frequent feeding is another advised protocol. Long-term management or standard therapy is individualized, wherein the usual goal is to normalize plasma glucose levels, provide an age-adjusted fasting tolerance, and avoid neurological symptoms associated with hypoglycemia. Surgery is performed to either remove a section or complete the pancreas in case of focal and diffuse congenital hyperinsulinism, respectively. The surgeries are not mandatorily curative, and the patients may continue to require frequent feeds and medications to prevent hypoglycemia post-surgery.
The first-line therapy is a potassium channel (KATP) channel opener for the treatment of the patients with CHI; Diazoxide and chlorothiazide belong to this class of drugs. Somatostatin analog such as octreotide is used as second-line therapy. Nifedipine or amlodipine belongs to calcium channel antagonists are merely used as a third-Line therapy, e.g., as an add-on treatment, in partial diazoxide/octreotide resistance, and/or following partial pancreatectomy.
The current emerging market of CHI possesses few potential drugs in late and mid-stage developments to be launched soon. Dasiglucagon is currently in the phase III stage of development followed by RZ358, CSI-Glucagon (Continuous Subcutaneous Glucagon Infusion), and Avexitide that are in phase II clinical developmental stage. Out of these therapies, RZ358 and CSI-Glucagon have already completed their phase II clinical developmental trial.
This section includes a glimpse of the Congenital Hyperinsulinism (CHI) 7MM market.
This section provides the total Congenital Hyperinsulinism (CHI) market size and market size by therapies in the United States.
The total Congenital Hyperinsulinism (CHI) market size and market size by therapies in Germany, France, Italy, Spain, and the United Kingdom are provided in this section.
The total Congenital Hyperinsulinism (CHI) market size and market size by therapies in Japan are provided.
This section focusses on the rate of uptake of the potential drugs recently launched in the Congenital Hyperinsulinism (CHI) market or expected to get launched in the market during the study period 2017-2030. The analysis covers Congenital Hyperinsulinism (CHI) market uptake by drugs; patient uptake by therapies; and sales of each drug.
This helps in understanding the drugs with the most rapid uptake, reasons behind the maximal use of new drugs and allow the comparison of the drugs on the basis of market share and size which again will be useful in investigating factors important in market uptake and in making financial and regulatory decisions.
Congenital Hyperinsulinism (CHI) Development Activities
The report provides insights into different therapeutic candidates in phase II, and phase III stage. It also analyzes key players involved in developing targeted therapeutics.
Pipeline Development Activities
The report covers the detailed information of collaborations, acquisition and merger, licensing and patent details for Congenital Hyperinsulinism (CHI) emerging therapies.
Competitive Intelligence Analysis
We perform competitive and market Intelligence analysis of the Congenital Hyperinsulinism (CHI) market by using various competitive intelligence tools that include-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.
Current Treatment Scenario, Marketed Drugs and Emerging Therapies: