Neurocrine Biosciences to Present Wide-Ranging One-Year Data from Phase 3 CAHtalyst™ Pediatric Study at Pediatric Endocrine Society 2025 Annual Meeting
Neurocrine Biosciences (NBIX) presented one-year data from its Phase 3 CAHtalyst™ Pediatric study of CRENESSITY™ (crinecerfont) in pediatric patients with classic congenital adrenal hyperplasia. The study, involving 103 pediatric patients aged 4-17, demonstrated sustained reductions in glucocorticoid doses while maintaining hormone control. Key findings include:
- Maintained reduction in glucocorticoid doses over 52 weeks - 32% of patients achieved physiologic glucocorticoid dose range by week 52 - Improvements in body mass index and insulin resistance - Hormone levels (ACTH, 17-OHP, androstenedione) remained below baseline - Generally well-tolerated with common side effects including headache (25%), abdominal pain (13%), and fatigue (7%)
The study consisted of a 28-week double-blind, placebo-controlled period followed by a 24-week open-label period, representing the largest interventional trial in classic CAH to date.
Neurocrine Biosciences (NBIX) ha presentato i dati a un anno dello studio di Fase 3 CAHtalyst™ Pediatric su CRENESSITY™ (crinecerfont) in pazienti pediatrici con iperplasia surrenalica congenita classica. Lo studio, che ha coinvolto 103 pazienti pediatrici di età compresa tra 4 e 17 anni, ha mostrato una riduzione costante delle dosi di glucocorticoidi mantenendo il controllo ormonale. I risultati principali includono:
- Riduzione mantenuta delle dosi di glucocorticoidi per 52 settimane
- Il 32% dei pazienti ha raggiunto il range fisiologico di dosaggio di glucocorticoidi entro la 52ª settimana
- Miglioramenti nell'indice di massa corporea e nella resistenza all'insulina
- I livelli ormonali (ACTH, 17-OHP, androstenedione) sono rimasti al di sotto dei valori basali
- Generalmente ben tollerato, con effetti collaterali comuni quali mal di testa (25%), dolore addominale (13%) e affaticamento (7%)
Lo studio ha previsto un periodo di 28 settimane in doppio cieco controllato con placebo seguito da un periodo in aperto di 24 settimane, rappresentando il più grande trial interventistico nella CAH classica fino ad oggi.
Neurocrine Biosciences (NBIX) presentó datos a un año de su estudio de Fase 3 CAHtalyst™ Pediátrico con CRENESSITY™ (crinecerfont) en pacientes pediátricos con hiperplasia suprarrenal congénita clásica. El estudio, que incluyó a 103 pacientes pediátricos de entre 4 y 17 años, demostró reducciones sostenidas en las dosis de glucocorticoides manteniendo el control hormonal. Los hallazgos clave incluyen:
- Reducción mantenida de las dosis de glucocorticoides durante 52 semanas
- El 32% de los pacientes alcanzó el rango fisiológico de dosis de glucocorticoides para la semana 52
- Mejoras en el índice de masa corporal y resistencia a la insulina
- Los niveles hormonales (ACTH, 17-OHP, androstenediona) se mantuvieron por debajo de la línea base
- Generalmente bien tolerado, con efectos secundarios comunes como dolor de cabeza (25%), dolor abdominal (13%) y fatiga (7%)
El estudio consistió en un periodo doble ciego controlado con placebo de 28 semanas seguido por un periodo abierto de 24 semanas, siendo el mayor ensayo intervencionista en CAH clásica hasta la fecha.
Neurocrine Biosciences(NBIX)는 고전적 선천성 부신 과형성증(Classic CAH) 소아 환자를 대상으로 한 CRENESSITY™(crinecerfont)의 3상 CAHtalyst™ 소아 연구 1년 데이터를 발표했습니다. 4세에서 17세 사이의 103명의 소아 환자가 참여한 이번 연구는 호르몬 조절을 유지하면서 글루코코르티코이드 용량을 지속적으로 감소시키는 결과를 보여주었습니다. 주요 결과는 다음과 같습니다:
- 52주 동안 글루코코르티코이드 용량 감소 유지
- 32%의 환자가 52주차에 생리적 글루코코르티코이드 용량 범위 도달
- 체질량 지수 및 인슐린 저항성 개선
- 호르몬 수치(ACTH, 17-OHP, 안드로스텐디온)가 기저치 이하 유지
- 일반적으로 내약성이 좋으며, 흔한 부작용으로 두통(25%), 복통(13%), 피로(7%)가 보고됨
이 연구는 28주간의 이중맹검 위약 대조 기간과 24주간의 공개 라벨 기간으로 구성되었으며, 지금까지 고전적 CAH에서 가장 큰 중재 임상시험입니다.
Neurocrine Biosciences (NBIX) a présenté des données à un an de son étude de phase 3 CAHtalyst™ pédiatrique sur CRENESSITY™ (crinecerfont) chez des patients pédiatriques atteints d'hyperplasie congénitale des surrénales classique. L'étude, impliquant 103 patients pédiatriques âgés de 4 à 17 ans, a démontré des réductions soutenues des doses de glucocorticoïdes tout en maintenant le contrôle hormonal. Les résultats clés incluent :
- Réduction maintenue des doses de glucocorticoïdes sur 52 semaines
- 32% des patients ont atteint la plage physiologique de doses de glucocorticoïdes à la semaine 52
- Améliorations de l'indice de masse corporelle et de la résistance à l'insuline
- Les niveaux hormonaux (ACTH, 17-OHP, androstènedione) sont restés inférieurs aux valeurs de base
- Généralement bien toléré avec des effets secondaires courants tels que céphalées (25%), douleurs abdominales (13%) et fatigue (7%)
L'étude comprenait une période en double aveugle contrôlée par placebo de 28 semaines suivie d'une période en ouvert de 24 semaines, représentant le plus grand essai interventionnel dans la CAH classique à ce jour.
Neurocrine Biosciences (NBIX) präsentierte Ein-Jahres-Daten aus der Phase-3-Studie CAHtalyst™ Pediatric mit CRENESSITY™ (crinecerfont) bei pädiatrischen Patienten mit klassischer kongenitaler adrenaler Hyperplasie. Die Studie mit 103 pädiatrischen Patienten im Alter von 4 bis 17 Jahren zeigte anhaltende Reduktionen der Glukokortikoiddosen bei gleichzeitiger Aufrechterhaltung der Hormonsteuerung. Wichtige Ergebnisse umfassen:
- Aufrechterhaltene Reduktion der Glukokortikoiddosen über 52 Wochen
- 32% der Patienten erreichten bis Woche 52 den physiologischen Glukokortikoiddosisbereich
- Verbesserungen im Body-Mass-Index und in der Insulinresistenz
- Hormonspiegel (ACTH, 17-OHP, Androstendion) blieben unter dem Ausgangswert
- Allgemein gut verträglich mit häufigen Nebenwirkungen wie Kopfschmerzen (25%), Bauchschmerzen (13%) und Müdigkeit (7%)
Die Studie bestand aus einer 28-wöchigen doppelblinden, placebokontrollierten Phase, gefolgt von einer 24-wöchigen offenen Phase, und stellt die bisher größte interventionelle Studie bei klassischer CAH dar.
- Sustained reduction in glucocorticoid doses maintained for up to one year
- 32% of patients achieved physiologic glucocorticoid dose range
- Improvements in clinical outcomes including BMI and insulin resistance
- No adrenal crises reported during the placebo-controlled period
- Successful hormone control maintained despite decreased glucocorticoid doses
- Some adverse reactions reported including headache (25%), abdominal pain (13%), and fatigue (7%)
- Not all patients achieved physiologic glucocorticoid dose range
Insights
Neurocrine's CRENESSITY shows promising long-term efficacy in pediatric CAH with glucocorticoid dose reduction and clinical improvements.
The one-year data from Neurocrine's Phase 3 CAHtalyst Pediatric study represents a significant advancement in classic congenital adrenal hyperplasia (CAH) treatment. CRENESSITY (crinecerfont) has demonstrated sustained efficacy, allowing for meaningful reductions in supraphysiologic glucocorticoid doses while simultaneously maintaining hormonal control.
What's particularly impressive is that 32% of patients achieved glucocorticoid doses within the physiologic range (≤11 mg/m²/d hydrocortisone equivalents) by week 52 - a critical milestone as chronic high-dose glucocorticoids cause substantial morbidity in these patients. The study showed mean glucocorticoid dose reductions of -2.9 mg/m²/d in the continuous CRENESSITY group.
From a metabolic perspective, the documented improvements in BMI and insulin resistance are especially noteworthy. CAH patients typically develop significant metabolic complications from chronic glucocorticoid exposure, including obesity, insulin resistance, and increased cardiovascular risk. The reductions in these parameters suggest CRENESSITY may mitigate these long-term complications.
The hormonal control data is equally compelling - maintaining adrenocorticotropic hormone, 17-hydroxyprogesterone, and androstenedione below baseline levels despite glucocorticoid reduction demonstrates the drug's effectiveness in addressing the fundamental pathophysiology of CAH by targeting corticotropin-releasing factor type 1 receptors.
The safety profile appears manageable with primarily mild adverse events (headache, abdominal pain, fatigue) and no reported adrenal crises during the double-blind period, which is reassuring given concerns about adrenal insufficiency when reducing glucocorticoid doses in CAH.
Phase 3 CAHtalyst Pediatric trial shows CRENESSITY enables glucocorticoid reduction with improved clinical outcomes in pediatric CAH patients.
The Phase 3 CAHtalyst Pediatric study represents one of the most robust clinical trials ever conducted in classic CAH, with 103 pediatric patients aged 4-17 years. The trial design was methodologically sound, utilizing a 28-week double-blind, placebo-controlled period followed by a 24-week open-label extension, allowing for both controlled efficacy assessment and longer-term safety and efficacy evaluation.
The 2:1 randomization to CRENESSITY versus placebo provided adequate statistical power while minimizing the number of patients exposed to placebo. The glucocorticoid dose titration protocol - maintaining stable doses for 4 weeks before allowing reductions - represents a cautious and clinically appropriate approach to prevent adrenal crises while testing the steroid-sparing effect.
The comprehensive endpoint selection is notable, including both biochemical markers (ACTH, 17-OHP, androstenedione) and clinically relevant outcomes (BMI, insulin resistance, hirsutism). This holistic approach demonstrates a thorough understanding of the multifaceted impact of CAH and its treatment.
Particularly impressive is the inclusion of analyses examining treatment patterns and changes in health states using data from the CAHtalog Registry, indicating a commitment to understanding real-world outcomes beyond the controlled trial environment. The examination of changes in glucocorticoid dosing regimens (including frequency reductions and shifts away from dexamethasone/prednisolone) addresses important quality-of-life considerations for patients managing this chronic condition.
The safety profile appears favorable with no adrenal crises reported during the placebo-controlled period, addressing a key concern with any intervention that allows glucocorticoid dose reduction in CAH patients.
One-Year Data Show Lasting Reductions in Glucocorticoid Doses and Improvements in Clinical Outcomes with CRENESSITY™ (crinecerfont) in Pediatric Patients with Classic Congenital Adrenal Hyperplasia
"These results demonstrate that CRENESSITY has the potential to transform the treatment landscape for children and adolescents living with classic congenital adrenal hyperplasia," said Eiry W. Roberts, M.D., Chief Medical Officer, Neurocrine Biosciences. "By simultaneously addressing the underlying hormonal imbalances and allowing for a reduction in glucocorticoid doses, we're seeing improvements in clinical outcomes, including reductions in body mass index and insulin resistance."
The Phase 3 CAHtalyst Pediatric study was part of the largest-ever interventional clinical trial program in classic congenital adrenal hyperplasia (CAH) including 103 pediatric patients, four to 17 years of age. The trial consisted of a 28-week, double-blind, placebo-controlled (DBPC) period, during which patients with classic CAH on supraphysiologic glucocorticoid (GC) doses were randomized 2:1 to receive CRENESSITY or placebo, and a 24-week, open-label (OL) period, during which all patients received CRENESSITY. During both the DBPC and OL periods, GC doses were kept stable for the first four weeks and then decreased as tolerated toward more physiologic levels while maintaining or improving androstenedione (A4) relative to Day 1 baseline. Three separate analyses examined the effect of CRENESSITY on:
- Changes in serum A4 levels and GC doses.
- Changes in adrenocorticotropic hormone (ACTH) and 17-hydroxyprogesterone (17-OHP) levels.
- Clinical outcomes.
Long-term, sustained reductions in high GC doses, in addition to improvements in key clinical outcomes, were observed in pediatric patients with up to one year of treatment with CRENESSITY:
- Reductions in supraphysiologic GC doses observed with 28 weeks of treatment with CRENESSITY were maintained during long-term treatment of up to one year.
- Importantly, for patients who were randomized to CRENESSITY during the DBPC period, the proportion who achieved a GC dose within the physiologic range (i.e., ≤11 mg/m2/d hydrocortisone equivalents) was stable from Week 28 (
30% ) to Week 52 (32% ).
- Importantly, for patients who were randomized to CRENESSITY during the DBPC period, the proportion who achieved a GC dose within the physiologic range (i.e., ≤11 mg/m2/d hydrocortisone equivalents) was stable from Week 28 (
- Pre-glucocorticoid ACTH, 17-OHP and A4 levels were reduced to below Day 1 baseline levels in children and adolescents with classic CAH taking CRENESSITY for up to one year, even after significant reductions in GC dose.
- Improvements were observed in body mass index (BMI) and insulin resistance in children and adolescents with classic CAH taking CRENESSITY for up to one year. In addition, hirsutism in female participants did not worsen, despite significant reductions in GC dose.
Measure | Baseline | Week 52 change | Week 52 change |
Mean GC dose | 16.4 mg/m2/d | -2.9 mg/m2/d | -1.1 mg/m2/d |
Mean BMI SD scores | 1.2 CRENESSITY; 1.1 placebo | -0.09 | -0.02 |
Average homeostatic | 2.8 CRENESSITY; 3.3 placebo | -0.72 | -1.3 |
Mean hirsutism VAS | 13.7 CRENESSITY; 21.6 placebo | -3.2 | +1.9 |
BMI: body mass index; SD: standard deviation; VAS: visual analog scale. |
CRENESSITY was generally well tolerated, with no adrenal crises reported in the DBPC period. The most common adverse reactions with CRENESSITY were headache (
GC Dosing Regimens in the Phase 3 CAHtalyst™ Adult and CAHtalyst Pediatric Studies
Additional data will be presented regarding changes in GC regimens in both adult and pediatric patients with classic CAH. Hydrocortisone dosing frequency was more likely to decrease with CRENESSITY, as was switching to dexamethasone- and prednisolone-free regimens. These changes may reduce both the CAH treatment burden and the risk of adverse effects of chronic treatment with high-dose GCs.
Additional poster presentations at the PES 2025 Annual Meeting include:
- Treatment Patterns and Changes in Health States in Pediatric Patients with Classic Congenital Adrenal Hyperplasia: An Analysis of Data from the CAHtalog™ Registry
- Crinecerfont Enables Reduction of Glucocorticoid Doses While Maintaining or Improving Androstenedione in Pediatric Patients with Classic Congenital Adrenal Hyperplasia: Subgroup Analyses from the CAHtalyst™ Pediatric Phase 3 Study
- Crinecerfont Allows for More Physiologic Glucocorticoid Treatment with Greater Reductions of Androstenedione in Pediatric Patients with Classic Congenital Adrenal Hyperplasia: Analyses of Individual Patient Data from the CAHtalyst™ Pediatric Study
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
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 enabled 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
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, CAHtalyst and CAHtalog 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-0027 05/2025
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FAQ
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