Phase 2 trial testing potential first-in-class Cushing’s treatment

Lu AG13909 is designed to block ACTH binding to its receptor on adrenals

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by Steve Bryson, PhD |

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Lundbeck has launched a Phase 2 clinical trial to assess the efficacy, safety, and tolerability of Lu AG13909, a potential first-in-class treatment for Cushing’s disease.

“We are pleased to advance this new approach to potentially treating unmet needs in Cushing’s disease, a condition that, when uncontrolled, is debilitating and increases mortality,” Johan Luthman, executive vice president, and head of research and development at Lundbeck, said in a company press release.

In Cushing’s disease, tumors in the brain’s pituitary gland trigger the excessive production of a signaling molecule called adrenocorticotropic hormone (ACTH), which stimulates the adrenal glands atop the kidneys to produce too much cortisol.

Over time, this hormonal imbalance results in a range of symptoms that include weight gain, fatigue, muscle weakness, high blood pressure, diabetes, and obesity. Without treatment, Cushing’s disease can be fatal due to secondary health complications, such as uncontrolled diabetes, infections, or heart disease.

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Blocking ACTH receptor binding

Cushing’s usually develops in people between the ages of 20-50 and is markedly more common in women. Certain genetic conditions tied to cancers in hormone-producing glands can also increase the risk of Cushing’s disease.

The first-line treatment for the condition is a surgical procedure called transsphenoidal adenomectomy to remove the disease-causing tumor in the pituitary gland. This can cure the disease in most patients, especially when the tumor is small. Radiation therapy that targets the tumor or cortisol-lowering medications may be used for people who don’t respond well to surgery.

Lu AG13909 is a potential first-in-class treatment for Cushing’s, meaning it uses a unique mechanism of action to drive its therapeutic effects. It’s an antibody-based therapy that’s designed to selectively block the binding of ACTH to its receptor, melanocortin-2, on the adrenal glands. The goal is to dampen ACTH signaling and reduce cortisol levels, thereby easing disease symptoms.

Lundbeck is also investigating Lu AG13909 to treat congenital adrenal hyperplasia, a rare disorder marked by a deficiency in enzymes that generate cortisol and aldosterone in the adrenal glands. This blockade leads to increased ACTH levels, stimulating the adrenal glands to release excess androgens, a group of male sex hormones. A Phase 1 clinical trial (NCT05669950) that’s assessing the effects of different doses of Lu AG13909 in adults with congenital adrenal hyperplasia is underway in the U.K.


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