The European Commission has approved Novartis’ drug Signifor as a treatment for the endocrine disorder Cushing’s disease where surgery is impossible or has failed.

Signifor (pasireotide) is the first targeted treatment for Cushing’s disease, in which a benign pituitary tumour triggers excess production of the hormone cortisol with debilitating effects.

The approval followed a phase III clinical trial in which patients given Signifor by regular injection experienced a sustained fall in cortisol levels, with normalisation achieved in a distinct patient sub-group.

Cushing’s disease is a rare but serious condition that affects one to two people per million each year. Symptoms include obesity, weakness and hypertension.

First-line treatment is surgical removal of the pituitary gland, but that is not always safe or successful.

Signifor already has orphan drug designation for treatment of Cushing’s disease.

In the PASPORT-CUSHINGS clinical trial, the largest phase III study of a treatment for Cushing’s disease, 162 patients received Signifor 900ug or 600ug twice daily for six months.

Mean urinary-free cortisol (UFC) levels were normalised in 26.3% and 14.6% of the patients respectively. The former patient group was judged to have achieved the primary trial endpoint of normalisation.

Reductions in UFC were rapid and sustained for both patient groups, with most patients experiencing a decrease within two months. Reductions in clinical symptoms were observed after six months in both patient groups, especially in those patients with normalised UFC levels.

“Patients with Cushing’s disease often struggle with a variety of debilitating health issues and previously were faced with a treatment approach limited to surgery,” said Ellen van Veldhuizen, board member of the Dutch Adrenal Society. “The approval of pasireotide as a new treatment option that may help patients with Cushing’s disease is welcome news.”

Herve Hoppenot, President of Novartis Oncology, commented: “As the first therapeutic option to specifically target Cushing’s disease, Signifor has the potential to redefine treatment of this debilitating disease.”

Novartis’ Signifor (pasireotide) has been recommended for approval by the CHMP for the rare hormonal disorder Cushing’s disease.

The somatostatin analogue would become the first approved medical therapy for the condition after it met the primary endpoint of normalising urinary-free cortisol (UFC) levels in a Phase III trial.

Hervé Hoppenot, President, Novartis Oncology, says the company is now “one step closer to being able to offer patients in Europe” a medical treatment.

Cushing’s disease is a debilitating and fatal disease which affects approximately one to two patients per million, per year. There are believed to be around a total of 20,000 people in Europe with the disease.

First-line therapy is the surgical removal of the tumour of the pituitary that produces too much adrenocorticotrophin (ACTH) and stimulates the adrenal glands to both grow and release excessive amounts of cortisol in to the blood. Symptoms include weight gain, bruising and high blood pressure.

Signifor has been designated as an orphan medicine since October 2009. In the Phase III PASPORT-CUSHINGS (PASireotide clinical trial PORTfolio - CUSHING'S disease) trial, the largest randomised study to evaluate a medical therapy in patients with the disease, it was shown to reduce levels of cortisol in urine by more than half in 41% of patients treated with a 900μg dose, and in more than a third of patients treated with a 600μg dose.

The European Commission will now decide whether to adopt the positive opinion of the CHMP. A decision is expected within the next three months and will apply to all 27 EU member states, plus Iceland and Norway.