Classic congenital adrenal hyperplasia (CAH) is a condition that is passed down in families. It is a serious condition that can be deadly if not treated. One of the treatments for classic CAH is glucocorticoids, but these medicines can cause serious side effects, such as slow growth in children, weight gain, diabetes, osteoporosis, or heart issues, if used at high doses or for long periods of time.
In late 2024, Crenessity became the first oral medicine approved by the FDA to be used alongside glucocorticoids to reduce the dose of steroids and potentially reduce the risk of side effects.
What Is Classic CAH?
CAH is a condition that affects how the adrenal glands make certain hormones. The adrenal glands make three important hormones that help the body work properly.
- Cortisol helps your body respond to stress and helps keep blood sugar stable and regulate blood pressure.
- Aldosterone helps control salt and water levels in your body as well as blood volume and blood pressure.
- Androgens, including testosterone, help start puberty and support normal growth and development.
People with CAH have a broken gene that does not work properly. The role of this gene is to make the right amount of an enzyme called 21-hydroxylase, which helps make sure the body has the right amounts of cortisol, aldosterone, and androgens. If your body does not have the right amount of 21-hydroxylase, your body might make too little cortisol and too much androgen.
There are different types of CAH. Classic CAH is a type of CAH that leads to high levels of androgens in the body. This type is less common than the other forms of CAH, but it can be deadly if left untreated.
How Does Crenessity Work for Classic CAH?
Crenessity works by reducing the amount of androgens that your body makes. It does this by attaching to a receptor called the corticotropin-releasing factor (CRF) type 1 receptor. When Crenessity is attached to this receptor, this prevents the release of a hormone called adrenocorticotropic hormone (ACTH). ACTH signals the body to make more androgens. Therefore, if your body is releasing less ACTH, less androgens will be made.
Will Crenessity Replace My Glucocorticoids?
It is very important that you keep taking your glucocorticoid medicine — such as dexamethasone, hydrocortisone, methylprednisolone, or prednisolone — exactly as your health care provider instructs while you are taking Crenessity. Do not lower your dose or stop taking your glucocorticoid medicine without talking to your health care provider.
The dose may need to be changed if you are taking other medicines that interact with Crenessity.
How Was Crenessity Studied in Children?
Study design
Crenessity was studied in 103 children. People in this study took Crenessity or a placebo pill two times daily with morning and evening meals for 28 weeks. Placebo pills do not contain an active medicine.
The dose of Crenessity was based on the weight of the child. Those who weighed between 10-20 kilograms (22-44 pounds) received 25 milligrams, those who weighed between 20-55 kilograms (44-121 pounds) received 50 milligrams, and those who weighed at least 55 kilograms (121 pounds) received 100 milligrams.
The researchers looked at a laboratory level called the androstenedione level to see if it went down after four weeks of treatment. In your body, androstenedione is used to make testosterone. They also looked to see if the dose of steroids went down.
To see if Crenessity was safe, the researchers collected information on the side effects people had during the study.
What types of children were included in the study?
To be in this study, children had to be between the ages of 2 and 17 and have a diagnosis of CAH. They also had to be taking steroids and have been at a stable dose for at least a month. People who were taking steroids for any condition other than CAH were not allowed to be in this study.
The average age of children in this study was about 12. About half (51%) were male. Most were White (63%), about 9% were Asian, 3% were Black, 11% were “other,” and 15% did not report their race or ethnic group.
More than 10% of the children had advanced bone age, early puberty, central precocious puberty, acne, short stature, ADHD, overweight or obesity, or irregular periods and excess hair growth on the face, chest, or back, known as hirsutism (in girls). A third of boys who had an ultrasound had testicular adrenal rest tumors.
What are the main benefits of Crenessity based on this study?
Children who took Crenessity had a decrease in their androstenedione level during the first four weeks of treatment. Children who took the placebo had an increase during the same time period.
Children who took Crenessity were able to decrease the dose of steroids during the study by about 18%. Children who took a placebo increased their dose of steroids by about 6%.
The number of people who had side effects in the study was similar for children treated with Crenessity and those who received the placebo.
Your results may differ from what was seen in clinical studies.
How Was Crenessity Studied in Adults?
Study design
Crenessity was studied in 182 adults with CAH. People in this study took 100 milligrams of Crenessity or a placebo pill two times a day with morning and evening meals. Placebo pills do not contain an active medicine.
To see if Crenessity worked, researchers looked to see how much the daily dose of glucocorticoids were able to be lowered after 24 weeks.
To see if Crenessity was safe, the researchers collected information on the side effects people had during the study.
What types of adults were included in the study?
To be in this adult study, people had to be 18 years of age or older, have a diagnosis of CAH, and be taking steroids at a stable dose for at least a month. People who were taking steroids for any condition other than CAH were not allowed to be in this study.
The average age of people in this study was about 31. About half (51%) were male. Most people were White (90%), about 3% were Asian, about 1% were Black or African American, about 1% identified as multiple races, about 2% were “other,” and data was not collected for about 3%.
More than 10% of adults had irregular periods, acne, hirsutism (in females), anxiety, depression, high blood pressure, high blood cholesterol levels, and weak bones. Almost half (48%) of men who had an ultrasound had testicular adrenal rest tumors.
What are the main benefits of Crenessity based on this study?
People who took Crenessity were able to lower their dose of glucocorticoids by about 27%, whereas those who took a placebo lowered theirs by only about 10%.
The number of people who had side effects in the study was similar for people treated with Crenessity and those who received the placebo.
Your results may differ from what was seen in clinical studies.
Are There Any Special Steps Required to Get Crenessity?
You must get Crenessity from a specialty pharmacy called PANTHERx RARE.
There is a patient support program called Neurocrine Access Support that can help you with insurance or cost-related issues. There may be cost assistance to help you afford Crenessity. You may have options even if you do not have health insurance.
Your health care provider can help you get started, or you can call 855-CRNSITY (855-276-7489) Monday through Friday from 8 a.m. to 8 p.m. ET. You can also visit www.nbiaccess.com/crenessity.