INDICATION CRENESSITY (crinecerfont) is indicated as adjunctive treatment to glucocorticoid replacement to control androgens in adults and pediatric patients 4 years of age and older with classic congenital adrenal hyperplasia (CAH).

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MANAGING CAH
IS A BALANCING ACT1,2

Balance is often elusive when treating with GCs alone3,4

~2/3 of patients with CAH taking GCs have poorly managed androgen levels3,5,6

Based on 2 large retrospective studies totaling 443 patients with CAH. Data included children and adults. “Poorly managed” was defined as elevated androgen levels and oversuppressed androgen levels.5,6

~1/3 of patients with CAH are treated for ≥1 cardiometabolic or bone comorbidity4

Based on a study of 244 patients with a median age of 33 years.4

In a multicenter study, the most common comorbidities in patients with CAH taking GCs included4:

  • Osteoporosis/osteopenia (59%)
  • Hyperlipidemia (23%)
  • Type 2 diabetes/hyperinsulinemia (22%)
  • Hypertension (14%)
Even when patients are well controlled clinically, high GC doses carry risks of long-term comorbidities.1
Addressing excess androgens often requires high GC doses, but these doses can lead to many short- and long-term comorbidities.1,2
Symptoms of excess ACTH and adrenal androgens1,2,7-10:
  • Early puberty
  • Growth issues
  • Fertility problems
  • TARTs/OARTs
  • Acne
  • Hirsutism
  • Anxiety
Comorbidities related to high GC doses1,2:
  • Obesity
  • Growth issues
  • Hypertension
  • Insulin resistance
  • Osteopenia and osteoporosis
  • Cognitive impairment
  • Mood disorders

Symptoms of androgen excess and high-dose GC comorbidities can affect patients’ quality of life.5

Cortisol deficiency in CAH leads to androgen excess3,11

Cortisol deficiency leads to3,11:
Number 1 IconLoss of negative feedback in HPA axis
Number 2 IconIncrease in

 CRF 

secretion
Number 3 IconIncrease in

 CRF1

 receptor activation
Number 4 IconIncrease in

 ACTH 

release
Number 5 IconOverproduction of

 adrenal androgens

Schematic showing how cortisol deficiency in CAH leads to androgen excess

95% of CAH cases are caused by 21-OH deficiency.10,12

Because of the 21-OH deficiency, the adrenal glands cannot make enough cortisol and, in many cases, aldosterone. Instead, they make excess androgens.3

Clinical Information

Now you can lower androgen levels without increasing GCs.

Novel MOA

See how CRENESSITY blocks CRF1 receptor activation.

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21-OH=21-hydroxylase; ACTH=adrenocorticotropic hormone; CAH=congenital adrenal hyperplasia; CRF=corticotropin-releasing factor; CRF1=corticotropin-releasing factor type 1; GC=glucocorticoid; HPA=hypothalamic-pituitary-adrenal; MOA=mechanism of action; OARTs=ovarian adrenal rest tumors; TARTs=testicular adrenal rest tumors.

REFERENCES

  • Merke DP, Auchus RJ. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. N Engl J Med. 2020;383(13):1248-1261. doi:10.1056/NEJMra1909786
  • Prete A, Auchus RJ, Ross RJ. Clinical advances in the pharmacotherapy of congenital adrenal hyperplasia. Eur J Endocrinol. 2021;186(1):R1-R14. doi:10.1530/EJE-21-0794
  • Mallappa A, Merke DP. Management challenges and therapeutic advances in congenital adrenal hyperplasia. Nat Rev. 2022;18(6):337-352. doi:10.1038/s41574-022-00655-w 
  • Righi B, Ali SR, Bryce J, et al. Long-term cardiometabolic morbidity in young adults with classic 21-hydroxylase deficiency congenital adrenal hyperplasia. Endocrine. 2023;80(3):630-638. doi:10.1007/s12020-023-03330-w 
  • Arlt W, Willis DS, Wild SH, et al. Health status of adults with congenital adrenal hyperplasia: a cohort study of 2023 patients. J Clin Endocrinol Metab. 2010;95(11):5110-5121. doi:10.1210/jc.2010-0917
  • Finkielstain GP, Kim MS, Sinaii N, et al. Clinical characteristics of a cohort of 244 patients with congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2012;97(12):4429-4438. doi:10.1210/jc.2012-2102
  • Hindmarsh PC, Geertsma K. Congenital Adrenal Hyperplasia: A Comprehensive Guide. Elsevier/Academic Press; 2017.
  • Sarafoglou K, Merke DP, Reisch N, Claahsen-van der Grinten H, Falhammar H, Auchus RJ. Interpretation of steroid biomarkers in 21-hydroxylase deficiency and their use in disease management. J Clin Endocrinol Metab. 2023;108(9):2154-2175. doi:10.1210/clinem/dgad134
  • Koren R, Koren S, Khashper A, Benbassat C, Pekar-Zlotin M, Vaknin Z. Ovarian adrenal rest tumor in congenital adrenal hyperplasia: is medical treatment the first line option? Arch Endocrinol Metab. 2021;65(6):841-884. doi:10.20945/2359-3997000000415 
  • Speiser PW, Arlt W, Auchus RJ, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(11):4043-4088. doi:10.1210/jc.2018-01865
  • Schröder MAM, Claahsen-van der Grinten HL. Novel treatments for congenital adrenal hyperplasia. Rev Endocr Metab Disord. 2022;23(3):631-645. doi:10.1007/s11154-022-09717-w
  • Auer MK, Nordenström A, Lajic S, Reisch N. Congenital adrenal hyperplasia. Lancet. 2023;401(10372):227-244. doi:10.1016/S0140-6736(22)01330-7

INDICATION

CRENESSITY (crinecerfont) is indicated as adjunctive treatment to glucocorticoid replacement to control androgens in adults and pediatric patients 4 years of age and older with classic congenital adrenal hyperplasia (CAH).

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

CRENESSITY is contraindicated in patients with hypersensitivity to crinecerfont or any excipients of CRENESSITY.

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions. A hypersensitivity reaction, including throat tightness, angioedema, and generalized rash, occurred in a subject after 3 days of treatment with CRENESSITY. If a clinically significant hypersensitivity reaction occurs, initiate appropriate therapy and discontinue CRENESSITY.

Risk of Acute Adrenal Insufficiency or Adrenal Crisis with Inadequate Concomitant Glucocorticoid Therapy. Acute adrenal insufficiency or adrenal crisis, which is potentially life-threatening, can occur in patients with underlying adrenal insufficiency who are on inadequate daily glucocorticoid doses, especially in situations associated with increased cortisol need, such as acute intercurrent illness, serious trauma, or surgical procedures. Continue glucocorticoids upon initiation of and during treatment with CRENESSITY. Do not reduce the glucocorticoid dose below the dose required for cortisol replacement. Patients should continue to use stress dosing of glucocorticoids in cases of increased cortisol need.

ADVERSE REACTIONS

In adult patients, the most common adverse reactions (at least 4% for CRENESSITY and greater than placebo) are fatigue, headache, dizziness, arthralgia, back pain, decreased appetite, and myalgia.

In pediatric patients, the most common adverse reactions (at least 4% for CRENESSITY and greater than placebo) are headache, abdominal pain, fatigue, nasal congestion, and epistaxis.

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.