Neurocrine Biosciences Presents CAHtalog Registry Analysis at ENDO 2025

Analysis reveals significant industry trends and economic implications

Release Date

2025-07-16

Category

Clinical Trial Event

Reference

Source

Breakthrough Clinical Results

Neurocrine Biosciences announced results from a new analysis of the CAHtalog registry, showing that most patients with classic congenital adrenal hyperplasia (CAH) experienced high glucocorticoid exposure and/or suboptimal disease control. The analysis, presented at ENDO 2025, used real-world data from 98 patients and demonstrated significant variability in glucocorticoid treatment regimens and frequent changes in health status. The findings highlight the challenges of managing CAH and underscore the need for therapies like CRENESSITY (crinecerfont), which aims to reduce androgen excess without high glucocorticoid doses. The data presented did not include CRENESSITY treatment data, as it was collected prior to the drug's commercial availability. Multiple additional presentations at ENDO 2025 showcased further data on CRENESSITY's efficacy and safety in both adult and pediatric CAH patients.

Key Highlights

  • Most CAH patients experienced high glucocorticoid exposure and/or suboptimal disease control.
  • Significant variability in glucocorticoid treatment regimens and frequent health status changes were observed.
  • Real-world data underscores the long-term challenges of managing CAH.
  • Multiple presentations at ENDO 2025 highlighted CRENESSITY's potential to improve CAH management.

Incidence and Prevalence

Global Estimates of Congenital Adrenal Hyperplasia Prevalence and Incidence

Congenital adrenal hyperplasia (CAH) occurs worldwide, with the most common form being due to 21-hydroxylase deficiency (21OHD). Recent epidemiological studies have provided updated prevalence estimates across different populations.

In Croatia, the calculated prevalence of 21-OHD in the general population is 1:18,000. However, a significantly higher prevalence exists in the Croatian Romani population at 1:3,750. This elevated prevalence is attributed to the homozygous cIVS2-13A/C-G pathological variant, with contributing factors including isolation, consanguinity, heterozygous advantage of the CYP21A2 gene pathological variant, and the bottleneck effect resulting from historical events such as the Romani Holocaust.

Among the Ossetian population (indigenous people of North Ossetia-Alania), the frequency of CAH caused by p.Trp230 variant in the HSD3B2 gene is 1:7,183 or 13.9 per 100,000 (95% CI: 1:1,874-1:38,447 or 3-53 per 100,000). The heterozygous carrier rate in this population was found to be 0.0236, with a total allele frequency of 0.0118*.

Ethnic-specific mutations in the CYP21A2 gene have been identified across different populations: - A large deletion is prevalent in Anglo-Saxons - A V281L (1685 G to T) mutation is prevalent in Ashkenazi Jews - An R356W (2109 G to A) mutation is prevalent in Croatians - An IVS2 AS -13 (A/C to G) mutation is prevalent in Iranians and Yupik-speaking Eskimos of Western Alaska - A Q318X (1994 C to T) mutation is prevalent in East Indians

In China, CAH was found to be the most frequent etiology of primary adrenal insufficiency in children, accounting for 83.4% of cases, with 97.2% of these being 21-hydroxylase deficiency CAH.

A Vietnamese study identified pathogenic variants in 97.5% of alleles, with the most common genotypes being I2g/I2g (15.35%), Del/Del (14.4%), Del/I2g (10.89%), p.R356W/p.R356W (6.44%), and exon 1-3 del/exon 1-3 del (5.44%).

In Sri Lanka, more than 70% of children with CAH had the salt-wasting form, with fewer affected males compared to females.

An Indian study found that 88.7% of subjects with 21-hydroxylase deficiency were positive for eight CYP21A2 mutations, with an overall mutation positivity of 97.2%.

After 21-hydroxylase deficiency, Steroid 11β-hydroxylase deficiency (11OHD) is the second most common form of CAH. Other rare types include lipoid congenital adrenal hyperplasia (LCAH), 3β-hydroxysteroid dehydrogenase deficiency (3β-HSD deficiency), and P450 oxidoreductase deficiency (PORD).

A 2022 study found that among genetic diseases causing neonatal hyperkalemia, CAH had the highest incidence (1.7%). A 2013 study reported the largest cohort of CAH patients to date, with 1,507 families having at least one affected member.

Economic Burden

Economic Burden of Treating Congenital Adrenal Hyperplasia in USA and Europe

United States Economic Burden

Recent data reveals a substantial economic burden associated with treating Congenital adrenal hyperplasia (CAH) in the United States. A 2022 study utilizing a US-based payer database with over 108 million members identified 551 CAH patients followed for more than 12 months. The analysis found that total annual health care expenditure for CAH patients was significantly higher at $7,677 compared to $4,203 for matched controls (P < 0.0001).

Patients with adrenal insufficiency, including CAH, experience more frequent inpatient hospital stays and spend eight to 10 times more days in the hospital annually than matched controls. The economic impact is further increased for patients on multiple steroid therapies, who incur higher expenditures compared to those using hydrocortisone therapy alone.

A 2009 cost-effectiveness study of newborn screening for CAH in the U.S. estimated an incremental cost-effectiveness ratio (ICER) of USD 292,000 per life year saved in traditional CEA and USD 255,700 in probabilistic CEA (2005 USD). The ICERs varied significantly based on assumptions, ranging from USD 30,900 in best-case scenarios to USD 2.9 million in worst-case scenarios per life year saved. This study concluded that CAH screening would likely not be considered cost-effective unless favorable assumptions were adopted. A limitation noted was the exclusion of outcomes such as correct gender assignment and quality of life.

A 2024 study indicated that published and unpublished cost-effectiveness analyses of CAH screening have yielded mixed findings due to methodological differences and variations in data sources for estimating health outcomes and associated costs.

Risk factors for hospitalization, which significantly impact costs, include noncommercial insurance (RR = 1.8; 95% CI [1.1-2.8]; P = 0.02) and age younger than 2 years (RR = 3.3 [2.2-4.8]; P < 0.0001).

Cost-Effectiveness of Screening

A 2021 cost-effectiveness analysis of newborn screening for CAH in Brazil found an NBS incremental cost of US$ 771,185.82 per death averted, yielding an ICER of US$ 25,535.95 per discounted life-year saved. This study concluded that CAH-NBS is important for preventing CAH mortality/morbidity, can reduce costs associated with adverse outcomes, and appears cost-effective.

The mortality rate was estimated at 11% in unscreened infants, while no deaths were reported in the screened cohort. Additionally, hospitalization occurred in 76% of unscreened salt-wasting patients compared to 58% in screened patients, indicating potential cost savings with early detection.

European Economic Burden

No specific recent data on the economic burden of CAH in Europe was available in the reviewed literature.

Drug used in other indications

Clinical Indications for CRENESSITY (crinecerfont) Beyond CAH

Based on a comprehensive review of available information, there are no additional indications beyond Congenital Adrenal Hyperplasia (CAH) for which CRENESSITY (crinecerfont) is currently being trialed.

The current clinical development of crinecerfont is specifically focused on treating 21-hydroxylase deficiency (21OHD), which is the most common form of CAH. Crinecerfont functions as a CRH receptor antagonist and is being investigated as a therapeutic option for children with classic 21OHD.

The available data indicates that crinecerfont has shown promise in its phase three trial for 21OHD, where it demonstrated the ability to: - Reduce glucocorticoid doses in patients - Lower androgen levels in individuals with 21OHD

This represents a promising new treatment approach for patients with this specific form of CAH, but there is no evidence of trials exploring its potential in other medical conditions or disease states.

Since there are no trials for other indications beyond CAH/21OHD, there is consequently no information available regarding intervention models, treatment protocols, or clinical trial designs for crinecerfont in other conditions.

The current research and development efforts for CRENESSITY appear to be exclusively concentrated on optimizing its efficacy and safety profile for patients with CAH, particularly the 21OHD variant.

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