Neurocrine Biosciences Announces New Results from Exploratory Analyses of the Phase 3 CAHtalyst™ Pediatric Study Demonstrating CRENESSITY™ Reduces Glucocorticoid Dosing While Maintaining or Improving Androstenedione Across Patient Subgroups

Rhea-AI Summary

Neurocrine Biosciences (NBIX) announced new results from subgroup analyses of the Phase 3 CAHtalyst™ Pediatric study for CRENESSITY™ (crinecerfont). The study, involving 103 patients (69 CRENESSITY, 34 placebo), demonstrated consistent positive results across all patient subgroups. Key findings showed that CRENESSITY significantly reduced androstenedione (A4) levels by -6.9 nmol/L versus +2.5 nmol/L for placebo at Week 4. Additionally, glucocorticoid doses were reduced by -18.0% versus +5.6% for placebo at Week 28, while maintaining or improving A4 levels. The drug was generally well-tolerated, with common side effects including headache, abdominal pain, fatigue, nasal congestion, and nosebleed. These results suggest CRENESSITY could significantly improve treatment outcomes for pediatric patients with classic congenital adrenal hyperplasia (CAH) by reducing reliance on high-dose glucocorticoids while controlling hormone levels.

Positive

• Significant reduction in androstenedione levels (-6.9 vs +2.5 nmol/L) compared to placebo
• Substantial decrease in glucocorticoid doses (-18.0% vs +5.6%) while maintaining hormone control
• Consistent positive results across all patient subgroups
• Generally well-tolerated safety profile

Negative

• Presence of adverse reactions including headache, abdominal pain, fatigue, nasal congestion and nosebleed

Insights

Clinical Endocrinology Specialist

CRENESSITY showed consistent efficacy across pediatric CAH patient subgroups, reducing androgen levels while enabling lower steroid doses with statistical significance.

The Phase 3 CAHtalyst Pediatric study results represent a potentially significant advance in managing classic congenital adrenal hyperplasia (CAH) in children. The dual benefit demonstrated – controlling androstenedione levels while reducing glucocorticoid doses – addresses both primary disease manifestations and treatment-related complications.

The data is particularly compelling because of the consistency across all patient subgroups regardless of demographics, baseline androstenedione levels, and baseline glucocorticoid doses. This suggests robust treatment efficacy across diverse patient populations. The statistical significance is strong with p=0.0002 for androstenedione reduction and p<0.0001 for glucocorticoid dose reduction.

Quantitatively, CRENESSITY demonstrated:

• Androstenedione reduction of -6.9 nmol/L versus +2.5 nmol/L with placebo at Week 4
• Glucocorticoid dose reduction of -18.0% versus +5.6% increase with placebo at Week 28

The clinical significance stems from the long-standing challenge in CAH management: high-dose glucocorticoids effectively control androgen excess but cause significant adverse effects affecting growth, metabolism, bone health, and quality of life. The ability to maintain hormonal control with lower steroid exposure could fundamentally improve the risk-benefit profile of CAH treatment.

The safety profile appears manageable with common reactions including headache, abdominal pain, fatigue, nasal congestion and nosebleed – relatively mild compared to the well-documented complications of chronic high-dose glucocorticoid therapy.

This approach represents the first significant innovation in pediatric CAH management in decades, potentially transforming treatment from merely controlling symptoms to addressing the underlying pathophysiology while reducing treatment burden.

- Data Consistent Across All Patient Subgroups, Including Demographic Subgroups, by Baseline Androstenedione Levels and by Baseline Glucocorticoid Dose

- Findings to be Presented at the 2025 Joint Congress of the European Society for Paediatric Endocrinology and the European Society of Endocrinology

SAN DIEGO, May 8, 2025 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced new results from subgroup analyses of the Phase 3 CAHtalyst™ Pediatric study. The analyses showed that, consistently across all of the different subgroups analyzed, pediatric patients with classic congenital adrenal hyperplasia maintained or improved their androstenedione levels with CRENESSITY™ (crinecerfont) while reducing glucocorticoid dosing. These data will be presented at the 2025 Joint Congress of European Society for Paediatric Endocrinology and the European Society of Endocrinology in Copenhagen, Denmark.

Overproduction of androstenedione, a key adrenal androgen, in pediatric patients with congenital adrenal hyperplasia (CAH) can lead to abnormal growth and development, premature puberty and various developmental challenges. For decades, high levels of androstenedione (A4) were treated with glucocorticoids (GCs) only.

"High-dose steroids are often accompanied by side effects and complications," said Eiry W. Roberts, M.D., Chief Medical Officer, Neurocrine Biosciences. "By enabling patients to maintain or improve their androgen levels while reducing their reliance on high-dose glucocorticoids, CRENESSITY has the potential to meaningfully enhance long-term outcomes, helping patients with both the hormonal imbalances that characterize CAH, as well as the challenges associated with chronic high-dose glucocorticoid treatment."

The CAHtalyst Pediatric study included 103 patients who were randomly assigned to receive either CRENESSITY (N=69) or a placebo (N=34) for 28 weeks. The primary endpoint was the least-squares (LS) mean change from baseline in A4 levels (before the morning GC dose) at Week 4. A key secondary endpoint was GC dose reduction at Week 28. Prespecified subgroup analyses of the primary endpoint and post-hoc subgroup analyses of GC dose reduction at Week 28 were conducted for region, sex, race, age, body mass index, pubertal stage and baseline A4 levels; and weight and baseline GC dose subgroups were also analyzed for GC dose reduction at Week 28. This comprehensive approach allowed for a thorough evaluation of treatment effects across diverse patient characteristics.

Across all subgroups, CRENESSITY enabled reduction of GC doses while maintaining or improving A4 levels:

• Substantial Reduction in Adrenal Androgens at Week 4: CRENESSITY significantly reduced A4 levels from baseline compared with placebo (overall, -6.9 versus +2.5 nmol/L; LS mean difference [LSMD]: -9.3 nmol/L; p=0.0002); subgroup analyses of A4 reduction at Week 4 were consistent with the results in the overall population.
• Substantial Reduction in GC Doses at Week 28: GC doses were significantly reduced from baseline with CRENESSITY (while maintaining or improving A4 levels) compared with placebo (overall, -18.0% versus +5.6%; LSMD: -23.5%; p<0.0001); subgroup analyses of GC reduction at Week 28 were consistent with the results in the overall population.

CRENESSITY was generally well tolerated in the CAHtalyst Pediatric study. The most common adverse reactions (≥4% for CRENESSITY and greater than placebo) were headache, abdominal pain, fatigue, nasal congestion and nosebleed.

The ability to reduce GC doses while simultaneously maintaining or improving androgen levels represents a significant advancement in CAH management. These results suggest that CRENESSITY may improve long-term outcomes in patients across various subgroups.

Additional presentations at the 2025 Joint Congress of the European Society for Paediatric Endocrinology and the European Society of Endocrinology include:

• Crinecerfont Improves Reproductive Hormones in Classic Congenital Adrenal Hyperplasia: 1-Year Results from the Phase 3 CAHtalyst™ Adult Study (Presentation RC13.5)
• A Double-blind Study of Modified-release Hydrocortisones, Chronocort versus Plenadren, in Adrenal Insufficiency (CHAMPAIN) (Presentation OC13.6)

About Congenital Adrenal Hyperplasia
Congenital adrenal hyperplasia (CAH) is a rare genetic condition that results in an enzyme deficiency that alters the production of adrenal steroid hormones, such as cortisol, aldosterone and adrenal androgens, which are essential for life. Approximately 95% of CAH cases are caused by variants of the CYP21A2 gene that leads to deficiency of the enzyme 21-hydroxylase. Severe deficiency of this enzyme leads to an inability of the adrenal glands to produce enough cortisol and, in approximately 75% of cases, aldosterone. Because individuals with CAH are still able to produce androgens, the unused precursors that would normally be used to make cortisol instead result in the production of excess amounts of androgens. If left untreated, CAH can result in salt wasting, dehydration and even death.

Historically, exogenous glucocorticoids (GCs) have been used to correct the endogenous cortisol deficiency, but doses higher than those for cortisol replacement (supraphysiologic) are needed to lower the elevated levels of adrenocorticotropic hormone (ACTH) and adrenal androgens. However, GC treatment at high doses has been associated with serious and significant complications of steroid excess, including metabolic issues such as weight gain and diabetes, cardiovascular disease and osteoporosis. Additionally, long-term treatment with high-dose GCs may have psychological and cognitive impacts, such as changes in mood and memory. Adrenal androgen excess has been associated with abnormal bone growth and development in pediatric patients, female health problems such as excess facial hair growth and menstrual irregularities, in addition to fertility issues in both sexes. The symptoms of high ACTH may include testicular adrenal rest tumors (TARTs) or ovarian adrenal rest tumors (OARTs).

About The CAHtalyst™ Pediatric Study
The Phase 3 CAHtalyst global registrational studies were designed to evaluate the safety, efficacy and tolerability of CRENESSITY in children and adults with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The CAHtalyst studies were the largest-ever interventional clinical trial program in classic CAH, including 285 pediatric and adult patients.

The CAHtalyst Pediatric study included 103 pediatric patients four to 17 years of age. The study tested two questions. The first question evaluated whether four weeks of CRENESSITY treatment could improve androgen control. The second question evaluated whether an additional 24 weeks of CRENESSITY treatment could enable customized glucocorticoid (GC) down-titration while androstenedione levels were maintained or improved.

Data from the CAHtalyst Phase 3 studies supported approval of CRENESSITY by the U.S. Food and Drug Administration in December 2024. The open-label extension treatment portions of both studies are ongoing.

About CRENESSITY™ (crinecerfont)
CRENESSITY is a potent and selective oral corticotropin-releasing factor type 1 receptor (CRF₁) antagonist developed to reduce and control excess adrenocorticotropic hormone (ACTH) and adrenal androgens through a non-glucocorticoid (GC) mechanism for the treatment of classic congenital adrenal hyperplasia (CAH). Antagonism of CRF₁ receptors in the pituitary has been shown to decrease ACTH levels, which in turn decreases the production of adrenal androgens and potentially the symptoms associated with CAH. The robust clinical study data demonstrate that lowering adrenal androgen levels with CRENESSITY enables lower, more physiologic dosing of GCs to replace missing cortisol.

CRENESSITY comes in capsules and an oral solution. The capsule formulation is available in 50 mg and 100 mg doses. The oral solution is available as a 50 mg/mL strength formulation. For adults 18 years of age and older, the recommended dosage is 100 mg twice daily taken orally with a meal. For pediatric patients four to 17 years of age weighing less than 55 kg (121 lbs), the recommended dosage is based on body weight and is administered twice daily, taken orally with a meal. For pediatric patients weighing more than 55 kg (121 lbs), the recommended dosage is 100 mg twice daily taken orally with a meal. Healthcare providers can work with patients to determine the appropriate formulation for use depending on patient needs. Patients receiving CRENESSITY should continue GC therapy for cortisol replacement.

Important Information

Approved Uses
CRENESSITY (crinecerfont) is a prescription medicine used together with glucocorticoids (steroids) to control androgen (testosterone-like hormone) levels in adults and children 4 years of age and older with classic congenital adrenal hyperplasia (CAH).

IMPORTANT SAFETY INFORMATION

Do not take CRENESSITY if you:
Are allergic to crinecerfont, or any of the ingredients in CRENESSITY.

CRENESSITY may cause serious side effects, including: 

Allergic Reactions. Symptoms of an allergic reaction include tightness of the throat, trouble breathing or swallowing, swelling of the lips, tongue, or face, and rash. If you have an allergic reaction to CRENESSITY, get emergency medical help right away and stop taking CRENESSITY.

Risk of Sudden Adrenal Insufficiency or Adrenal Crisis With Too Little Glucocorticoid (Steroid) Medicine. Sudden adrenal insufficiency or adrenal crisis can happen in people with congenital adrenal hyperplasia who are not taking enough glucocorticoid (steroid) medicine. You should continue taking your glucocorticoid (steroid) medicine during treatment with CRENESSITY. Certain conditions such as infection, severe injury, or shock may increase your risk for sudden adrenal insufficiency or adrenal crisis. Tell your healthcare provider if you get a severe injury, infection, illness, or have planned surgery during treatment. Your healthcare provider may need to change your dose of glucocorticoid (steroid) medicine.

Before taking CRENESSITY, tell your healthcare provider about all of your medical conditions, including if you are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of CRENESSITY in adults include tiredness, headache, dizziness, joint pain, back pain, decreased appetite, and muscle pain.

The most common side effects of CRENESSITY in children include headache, stomach pain, tiredness, nasal congestion, and nosebleeds.

These are not all the possible side effects of CRENESSITY. Call your healthcare provider for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch at www.fda.gov/medwatch or call 1-800-FDA-1088.

Dosage Forms and Strengths: CRENESSITY is available in 50 mg and 100 mg capsules, and as an oral solution of 50 mg/mL.

Please see full Prescribing Information.

About Neurocrine Biosciences, Inc.
Neurocrine Biosciences is a leading neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs. We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neurological, neuroendocrine and neuropsychiatric disorders. The company's diverse portfolio includes FDA-approved treatments for tardive dyskinesia, chorea associated with Huntington's disease, classic congenital adrenal hyperplasia, endometriosis* and uterine fibroids,* as well as a robust pipeline including multiple compounds in mid- to late-phase clinical development across our core therapeutic areas. For three decades, we have applied our unique insight into neuroscience and the interconnections between brain and body systems to treat complex conditions. We relentlessly pursue medicines to ease the burden of debilitating diseases and disorders, because you deserve brave science. For more information, visit neurocrine.com and follow the company on LinkedIn, X and Facebook. (*in collaboration with AbbVie)  

The NEUROCRINE BIOSCIENCES Logo, NEUROCRINE and YOU DESERVE BRAVE SCIENCE are registered trademarks of Neurocrine Biosciences, Inc. CRENESSITY and CAHtalyst are trademarks of Neurocrine Biosciences, Inc.

Forward-Looking Statements
In addition to historical facts, this press release contains forward-looking statements that involve a number of risks and uncertainties. These statements include, but are not limited to, statements regarding the potential benefits to be derived from CRENESSITY for the treatment of classic congenital adrenal hyperplasia (CAH); the value and benefits CRENESSITY brings to patients with CAH; the ability of Neurocrine Biosciences to ensure patients have access to CRENESSITY; and whether the results from our clinical trials of CRENESSITY are indicative of real-world results. Factors that could cause actual results to differ materially from those stated or implied in the forward-looking statements include, but are not limited to, the following: risks and uncertainties associated with Neurocrine Biosciences' business and finances in general, as well as risks and uncertainties associated with the commercialization of CRENESSITY, including the extent to which patients and physicians accept and adopt CRENESSITY; whether CRENESSITY receives adequate reimbursement from third-party payors; risks and uncertainties relating to competitive products and technological changes that may limit demand for CRENESSITY; risks associated with the Company's dependence on third parties for development and manufacturing activities related to CRENESSITY, and the ability of the Company to manage these third parties; risks that additional regulatory submissions for CRENESSITY may not occur or be submitted in a timely manner; risks that the FDA or other regulatory authorities may make adverse decisions regarding CRENESSITY; risks that post-approval CRENESSITY commitments or requirements may be delayed; risks that CRENESSITY may be precluded from commercialization by the proprietary or regulatory rights of third parties, or have unintended side effects, adverse reactions or incidents of misuse; risks and uncertainties relating to competitive products and technological changes that may limit demand for CRENESSITY; and other risks described in the Company's periodic reports filed with the Securities and Exchange Commission, including without limitation the Company's quarterly report on Form 10-Q for the quarter ended March 31, 2025. Neurocrine Biosciences disclaims any obligation to update the statements contained in this press release after the date hereof other than required by law.

© 2025 Neurocrine Biosciences, Inc. All Rights Reserved. CAP-CFT-US-0021   05/2025

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FAQ

What were the main results of NBIX's Phase 3 CAHtalyst Pediatric study for CRENESSITY?

The study showed CRENESSITY reduced androstenedione levels by -6.9 nmol/L vs +2.5 nmol/L for placebo at Week 4, and decreased glucocorticoid doses by -18.0% vs +5.6% at Week 28, while maintaining hormone control.

How many patients participated in Neurocrine's CAHtalyst Pediatric trial?

The study included 103 patients, with 69 receiving CRENESSITY and 34 receiving placebo over 28 weeks.

What are the common side effects of CRENESSITY reported in the NBIX trial?

The most common adverse reactions were headache, abdominal pain, fatigue, nasal congestion and nosebleed, occurring in ≥4% of patients and more frequently than placebo.

How does CRENESSITY benefit patients with congenital adrenal hyperplasia (CAH)?

CRENESSITY helps patients maintain or improve androgen levels while reducing their reliance on high-dose glucocorticoids, potentially enhancing long-term outcomes and reducing steroid-related complications.

What was the primary endpoint in the NBIX CAHtalyst Pediatric study?

The primary endpoint was the least-squares mean change from baseline in androstenedione (A4) levels before the morning glucocorticoid dose at Week 4.