The congenital hyperinsulinism (CHI) therapeutic landscape is experiencing significant momentum, with multiple pharmaceutical companies advancing promising treatments through various stages of clinical development. According to DelveInsight's comprehensive pipeline analysis, the field encompasses 4+ key companies working on 6+ treatment therapies for this rare genetic disorder.
Regulatory Milestones Drive Market Progress
Recent regulatory developments have marked important progress for the CHI pipeline. In January 2025, Rezolute announced that the FDA granted Breakthrough Therapy Designation to RZ358 (ersodetug) for treating hypoglycemia associated with congenital hyperinsulinism. This designation followed the FDA's removal of partial clinical holds on the drug in September 2024, enabling the inclusion of US participants in the ongoing global sunRIZE Phase III trial.
Zealand Pharma faced regulatory challenges when the FDA issued a Complete Response Letter (CRL) in October 2024 for Part 1 of the New Drug Application (NDA) for dasiglucagon. The application sought approval for preventing and treating hypoglycemia in pediatric patients aged seven days and older with CHI for up to three weeks of dosing. The company plans to resubmit its NDA to the FDA in early 2024.
Pipeline Diversity Across Development Stages
The CHI pipeline demonstrates therapeutic diversity across multiple development phases. Key emerging therapies include CRN-04777 from Crinetics Pharmaceuticals, HM 15136 from Hanmi Pharmaceutical, RZ358 from Rezolute, and dasiglucagon from Zealand Pharma. These treatments represent various molecular approaches, including recombinant fusion proteins, small molecules, monoclonal antibodies, peptides, and gene therapy approaches.
The pipeline spans from late-stage Phase III products to early-stage Phase I candidates, with products categorized under different routes of administration including oral, parenteral, intravenous, subcutaneous, and topical formulations. DelveInsight's analysis indicates that dasiglucagon is currently in Phase III development, while RZ358 and avexitide are in Phase II clinical development stages.
Market Dynamics and Growth Projections
The congenital hyperinsulinism market is expected to surge due to increasing disease prevalence and awareness during the forecast period. DelveInsight's estimates indicate that in 2023, diagnosed prevalent cases of CHI in the United States accounted for around 20% of total cases across the 7MM (seven major markets). The diffuse type comprised approximately 75% of CHI cases in the United States in 2023, with ABCC8 and KCNJ11 mutations being more frequently observed compared to other genetic variants.
The market dynamics are driven by several factors, including the presence of only one approved therapy, which provides opportunities for research and development initiatives. Increasing research activities, disease awareness, and support systems are expected to drive long-term market growth. However, the market faces barriers including high treatment costs, complications associated with insulin formulation, and significant gaps in proper diagnosis and management of CHI.
Clinical Trial Activities and Strategic Developments
Recent clinical developments include Sidra Medicine's conduct of the industry-sponsored 'sunRIZE' trial focused on pediatric congenital hyperinsulinism in December 2024. This Phase III trial, led by Rezolute, represents the first pharmaceutical trial following the launch of Sidra's Clinical Trials Program, aimed at enhancing treatment options for rare and complex diseases in the Arab region.
Strategic acquisitions have also shaped the landscape, with Amylyx Pharmaceuticals acquiring avexitide from Eiger BioPharmaceuticals in July 2024. Avexitide has been investigated for treating hyperinsulinemic hypoglycemia, adding to the therapeutic options under development.
Understanding Congenital Hyperinsulinism
Congenital hyperinsulinism is a rare genetic disorder characterized by excessive insulin production and secretion by pancreatic beta cells. This abnormal insulin regulation leads to hypoglycemia (low blood sugar), with infants and young children experiencing lethargy, irritability, and feeding difficulties. Repeated hypoglycemic episodes increase risks for serious complications including breathing difficulties, seizures, intellectual disability, vision loss, brain damage, and coma.
The condition affects blood sugar regulation through abnormal insulin secretion patterns, making effective treatment crucial for preventing long-term complications. Current treatment approaches focus on managing hypoglycemic episodes and maintaining stable blood glucose levels.
Future Market Outlook
The CHI pipeline holds promise for addressing significant unmet medical needs in this rare disease area. With multiple therapies advancing through clinical development and regulatory pathways, the market is positioned for substantial growth during the 2020-2034 forecast period. The combination of breakthrough therapy designations, ongoing Phase III trials, and increasing disease awareness suggests a transformative period ahead for CHI treatment options.
Key companies including Zealand Pharma, Rezolute, Eiger BioPharmaceuticals, Crinetics, AmideBio, and Hanmi Pharmaceutical continue to advance their respective therapeutic candidates, with the potential to significantly revolutionize CHI market dynamics upon successful development and regulatory approval.
