By Phyllis Speiser, MD, with Keri Wiginton
Phyllis Speiser is emeritus professor of pediatrics at Zucker School of Medicine at Hofstra-Northwell and associate investigator at The Feinstein Institute for Medical Research of Northwell Health. She is a retired pediatric endocrinologist with 40 years of experience in the field of adrenal disorders.
Speiser was a consultant to Neurocrine Biosciences and was a principal investigator in the pediatric trial for crinecerfont (Crenessity). The insights shared here represent her knowledge as a medical professional.
Classic congenital adrenal hyperplasia (CAH) is a rare genetic condition that disrupts hormone balance.
If you have CAH, the adrenal glands make too little cortisol, a hormone you need to function. This genetic defect causes the body to overproduce androgens (testosterone-like hormones). This can cause problems in both males and females, such as growth disruption, early puberty, irregular periods, or infertility. Females born with classic CAH can be born with external sex organs that resemble male genitalia.
The defect in CAH may also cause a deficiency of another adrenal hormone called aldosterone. Without these hormones, classic CAH can lead to shock , coma, or death.
For decades, treatment has been the same: steroids like hydrocortisone in high doses. But in December 2024, the FDA approved crinecerfont (Crenessity) – the first new drug for classic CAH in 70 years and the only one made specifically for the condition.
Who Is This Treatment For?
Crinecerfont is approved for people ages 4 and up with classic CAH. It’s designed to lower levels of androgens, which may reduce the need for high doses of glucocorticoids. Those are cortisol-like steroids such as hydrocortisone, prednisone, and dexamethasone.
Kids with CAH might benefit the most since they’re still growing, and high steroid doses can affect development. But adults could also see improvements, especially if they struggle with side effects from long-term steroid treatment or have trouble keeping hormone levels steady.
The drug isn’t a replacement for steroids. It’s meant to help keep hormone levels in balance while potentially reducing steroid-related side effects. Whether it’s the right choice depends on your specific situation.
What’s Different About This Drug?
To understand why crinecerfont is a breakthrough, it helps to know how hormone imbalances happen in CAH.
Your pituitary gland is a pea-sized organ in the base of your brain. It makes adrenocorticotropic hormone (ACTH), a chemical that signals the adrenal glands to make cortisol. But if you don’t make enough cortisol, the body tries to fix the problem by pumping out more ACTH. This causes the adrenal glands to make too many androgens.
Steroids like hydrocortisone help replace missing hormones, but they don’t continuously and efficiently stop the body from overproducing ACTH. To keep everything in balance, people with CAH often need lifelong treatment with higher-than-normal steroid doses. This can cause unwanted side effects like weight gain, high blood pressure, weaker bones, and slower growth in kids.
Crinecerfont works in a totally different way. Instead of replacing hormones, it blocks a receptor in the brain that triggers excess ACTH production. By turning down this overactive system, the body makes fewer androgens. As a result, you may need lower steroid doses to balance your hormones.
It’s not a cure, but it could reduce steroid-related side effects and improve quality of life.
How Fast Does It Work? How Effective Is It?
In clinical trials, people saw improvement within four weeks. Their hormone levels dropped to a healthier range in that time, showing that the drug was doing what it was supposed to. It also helped people lower their steroid doses, which is a major goal of treatment.
These benefits lasted through the entire 28-week study and were seen in both kids and adults.
Now that the drug is approved, doctors will be watching to see if these effects hold up in large groups of people with CAH who are treated over a longer time period.
How Do You Take Crinecerfont?
You take it by mouth twice a day with food – once in the morning with your usual steroid medications and again before bed. This timing helps keep hormone levels steady throughout the day and overnight.
As a side note, hydrocortisone, a common steroid for CAH, doesn’t last long in the body. This is why it’s often given instead of stronger steroids like prednisone or dexamethasone. Those can last longer but also come with more side effects.
Are There Any Side Effects? How Do You Manage Them?
In clinical trials, the most common side effects in adults were fatigue, headache, dizziness, and joint pain. Kids mostly reported headaches, belly pain, tiredness, and nasal congestion. Most of these symptoms were temporary, mild, and didn’t cause people to stop taking the drug.
Both the adult and pediatric trials happened during the COVID-19 pandemic, which makes it harder to tell if symptoms like headaches and fatigue were caused by the drug or a viral infection.
Is This Treatment Safe?
So far, very few serious side effects have been reported. But as with any new medication, doctors will keep an eye on patients to watch for any unexpected issues.
Crenessity comes with a warning about a serious condition called adrenal crisis. This can happen if someone with adrenal insufficiency doesn’t get enough of the right steroids when their body is under stress and needs extra cortisol. Your doctor can go over when you might need a “stress dose.”
Also, if you're allergic to Crenessity or any of its ingredients, you shouldn’t take it.
How Long Do You Take It?
That’s not entirely clear yet. Some people may need it long-term, while others might use it only during certain phases of life – like puberty, when hormone levels are harder to control.
In teenagers, for example, doctors sometimes increase steroid doses to balance hormones. But higher doses can lead to weight gain, high blood pressure, and other unwanted side effects. In those cases, crinecerfont could help reduce steroid use for a few years and then be stopped once things stabilize.
Ultimately, how long someone takes it will depend on their individual needs and how well the medication works for them.
How Often Will You Need Follow-Ups?
Doctors will want to monitor you closely at first to make sure the medicine is working and there are no major side effects.
For kids, doctors will likely schedule visits every four to six months – or more often if there are any issues. For adults, follow-ups may not be as frequent, but it’s still a good idea to check in with a doctor at least every six to 12 months.
If it’s hard to get an appointment with a specialist, like an endocrinologist, your primary care doctor may be able to help monitor your progress.
Will Insurance Cover It?
FDA approval makes it easier for insurance companies to cover new medications, but every plan is different. They each have a list of preferred drugs and out-of-pocket costs, so coverage will likely vary for each person.
Many doctors are just starting to prescribe crinecerfont, so insurance coverage is something we’ll know more about in the future. For now, it’s best to call your provider to ask about your coverage.
The drug’s maker also offers a financial assistance program called Neurocrine Access Support. You can visit the Crenessity website to see if you qualify.
How Can You Find Out if Crinecerfont Is Right for You?
Start by talking with an endocrinologist. They’ll consider your lab results and several other things when deciding if this medication is right for you. For children, doctors will look at things like growth, weight, blood pressure, and how well hormone levels are controlled.
Like I said earlier, this drug may be especially helpful during times when hormone management is more difficult, like puberty. Some adults with CAH-related infertility may also benefit, though its effects during pregnancy haven’t been studied yet.
Keep in mind that crinecerfont isn’t a replacement for steroids. It’s an add-on treatment designed to lower androgen levels and reduce the need for high steroid doses, which may lessen side effects.
How Carefully Was This Drug Studied?
Crinecerfont went through rigorous clinical trials, even during the challenges of the COVID-19 pandemic. That means researchers followed strict guidelines to ensure the results were as accurate as possible.
In the pediatric trial, more people enrolled than expected, and an impressive 95% of them completed the full study. That’s rare, since many people tend to drop out of trials due to side effects or other issues. What’s more, the results showed that the drug worked as expected.
And both the pediatric and adult trials were published in a respected medical journal, The New England Journal of Medicine, which is a strong endorsement of the research quality and adds to the trustworthiness of the findings.
Like any new medication, it will take time and real-world use to fully understand its long-term impact. But based on the clinical trials, crinecerfont is a promising new option for people with CAH. For many, it could mean better hormone balance, fewer steroid-related side effects, and improved quality of life.