The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended granting a marketing authorization for ketoconazole (Ketoconazole HRA; Laboratoire HRA Pharma) for the treatment of Cushing's syndrome, a rare hormonal disorder sometimes called hypercortisolism.
Cushing's syndrome is characterized by an excess of the hormone cortisol in the blood, which may be caused by a tumor. Treatment options currently available in the European Union include surgery to remove the tumor responsible for the high cortisol levels and radiotherapy, as well as several medicines that reduce the production of cortisol.
But pharmacological options remain very limited, and there is an unmet medical need for additional treatments, especially when surgery fails or for patients who cannot undergo surgery or take other medications. For this reason, the EMA's CHMP evaluated the medicine under expedited review.
The opinion adopted by the CHMP at its September 2014 meeting is an intermediary step on Ketoconazole HRA's path to patient access.
The CHMP opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorization. Once a marketing authorization has been granted, decisions about price and reimbursement will then take place at the level of each member state considering the potential role/use of this medicine in the context of the national health system of that country.
The recommendation is that Ketoconazole HRA is to be prescribed only by physicians specialized in treating Cushing's syndrome, as the dosing needs to be individualized for each patient.
This is because oral ketoconazole was previously suspended in the European Union for the indication it was first approved for, fungal infections, due to risk for liver injury. The US Food and Drug Administration (FDA) also decreed, at the same time, that doctors should no longer prescribe ketoconazole tablets as a first-line therapy for any fungal infection, for the same reason.
Information will be sent to healthcare professionals to allow them to advise patients and prescribe the medicine safely and effectively.
A Medicine Used Off-Label for More than 30 Years
Doctors have used ketoconazole to treat Cushing's syndrome for more than 30 years, although it has never been authorized for this indication in the European Union. The drug is also frequently used off-label in the United States and elsewhere for this purpose.
The CHMP's recommendation builds on information from published literature and documented off-label use in clinical practice.
At the time of the suspension of ketoconazole for fungal infections, healthcare professionals and patients were concerned that ketoconazole would no longer be available for patients with Cushing's syndrome.
The CHMP therefore reviewed Ketoconazole HRA through accelerated assessment to facilitate patients' access to a fully authorized medicine as soon as possible with evidence-based information for patients and doctors.
When assessing Ketoconazole HRA for the treatment of Cushing's syndrome, the CHMP considered that "in this rare and potentially life-threatening condition, the medicine's benefits are greater than its risks, which can be manageable in clinical practice by specific measures mitigating the risk of liver toxicity, including close monitoring of the patients' liver function."
In 2012, it was estimated that the disease affected approximately 46,000 people in the European Union. Cushing's syndrome is a long-lasting condition that can be life-threatening because of its complications, including diabetes, high blood pressure, and depression.
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Cite this: EU Looks to Okay Ketoconazole for Use in Cushing's Syndrome - Medscape - Sep 26, 2014.