Good news for CAH (Congenital Adrenal Hyperplasia) patients! Let's talk about Crinecerfont

If you or someone in your family has a condition called Congenital Adrenal Hyperplasia (CAH), this will be very important news for you. After 70 years, a new treatment specifically for this disease has now been approved. This is really a great hope for people living with CAH. So let's take a look at what this new drug is, how it works, and what are the benefits.

First, let's understand, what is CAH?

Simply put, CAH is a genetic disease that affects our adrenal glands. These glands are located above our kidneys. They produce several hormones that are essential for our body.

Think of the adrenal gland as a factory. The main product of this factory is a hormone called cortisol. This is a very important hormone that helps our body cope with stress, illness, and danger.

When cortisol levels in a healthy person drop, the brain (like a factory manager) sends a signal (order) called ACTH to the adrenal gland to "make cortisol." But in someone with CAH, the adrenal gland lacks a key enzyme, or 'worker', needed to make cortisol. So no matter how much ACTH the brain sends, the factory can't make cortisol.

This raises two questions:

1. The body does not produce the necessary cortisol .

2. As ACTH signals from the brain continue to flow, another type of hormone produced by the adrenal gland , called androgens, is produced in excess .

These androgens (e.g. testosterone) are male hormones. Both men and women need some of them, but in CAH, they become too high. This can cause early puberty, infertility, and other problems with a child's development .

For decades, the main treatment for this has been to administer steroids (glucocorticoids) that act like cortisol externally. This not only replaces the cortisol that the body lacks, but also controls the ACTH signal from the brain, reducing the production of androgens. However, the problem is that this requires taking higher doses of steroids than normal for a long time. This can cause a lot of side effects, such as weight gain, thinning bones, and sleep problems .

How did you find this new medicine?

Scientists wondered if there was another solution to this steroid problem. Instead of giving a lot of steroids externally, what if we found a way to directly reduce the ACTH signal coming from the brain?

That's where they found a new target. It was a receptor in the brain called CRF1. When cortisol levels drop, the ACTH signal is triggered by CRF1. In CAH, this process is disrupted.

So scientists thought, if we block this CRF1, we could reduce the production of ACTH, right? If that happens, the production of androgens will also be controlled, and the dose of steroids that the patient needs to take will also be reduced.

Tests done before giving a medicine to people

A new drug cannot be given to people as soon as it is discovered. It needs to undergo a series of tests to confirm whether it is safe and effective. The Crinecerfont drug went through all these steps.

1. Laboratory and animal testing: The first step is to test the drug on cells and animals in the laboratory. This is to determine whether the drug is toxic or if it will harm organs. Just imagine, only about one in 10,000 new drugs passes all these hurdles and is approved.

2. Clinical Trials: After animal testing is successful, human trials are conducted in several stages.

How are the test results for Crinecerfont?

The trials conducted on this drug have yielded very good results. Especially the Phase II & Phase III trials are very important.

Phase II - Younger children's results

Here, a small group of young children (ages 14-17) with CAH were given the drug for 14 days and the changes in their hormone levels were observed. The results were surprising.

• ACTH (brain signal) decreased by 57% .
• 17-OHP (an indicator of androgen production) decreased by 69% .
• Androstenedione (a type of androgen) decreased by 58% .

Phase III - Results of large groups

Encouraged by these results, scientists conducted two large trials using adults and children, where some were given the drug Crinecerfont and others were given a placebo that looked like a drug but had no effect.

These results clearly show that Crinecerfont helps control androgen levels, while also reducing the dose of steroids that can be harmful to patients in the long term.

How safe is this medicine?

Studies have shown that this drug has few serious side effects. Most of the reported side effects are minor and temporary.

• Fatigue
• Headache
• Cold or stuffy nose
• Muscle or abdominal pain
• Joint pain

The only major warning that comes with this medication is that if you don't take the exact dose of steroids your doctor prescribes , your cortisol levels can drop dangerously low, leading to a life-threatening condition called adrenal insufficiency. However, no one who took the medication properly in the studies has experienced this condition . Therefore, it is very important to follow your doctor's instructions.

New hope for CAH treatment

Because of these successful results, the FDA (the main agency that approves drugs) in the United States has granted special approval for this drug. Crinecerfont (brand name Crenessity) is not a cure for CAH. However, it is a major step forward in the treatment of CAH.

Doctors can now prescribe this medication in addition to your current steroid treatment (add-on therapy) . This can help reduce your steroid dose. This means that you may experience fewer side effects from steroids, better control your hormone levels, and have a better quality of life.

CAH, Congenital Adrenal Hyperplasia, Crinecerfont, Crenessity, Hormones, Adrenal Glands, Cortisol, Androgen, Steroids, Genetic Diseases, Pediatrics, New Drugs, ACTH