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Acromegaly Drug Pasireotide LAR Shows Promise in Late-Stage Trial

Treatment achieves biochemical disease control

Positive results have been reported from a pivotal phase III study of the investigational therapy pasireotide long-acting release (LAR) (Signifor LAR, Novartis) in patients with acromegaly for whom current standard of care provides inadequate disease control.

The study showed that patients taking pasireotide LAR achieved greater disease control compared with continued treatment with the standard somatostatin analogue therapy octreotide LAR (Sandostatin LAR, Novartis) or lanreotide autogel (Somatuline Autogel, Ipsen).

The new data were presented at the 16th European Congress of Endocrinology, being held May 3–7 in Warsaw, Poland.

Acromegaly is caused by a benign (noncancerous) tumor within the pituitary gland that secretes excess growth hormone (GH), leading to elevated levels of insulin-like growth factor-1 (IGF-1). This combined effect of elevated GH and IGF-1 levels causes the enlargement of body parts, including the hands, feet, and facial features, along with serious co-morbidities, such as cardiovascular, metabolic, and respiratory diseases.

If exposed to long-term elevated levels of GH and IGF-1, patients with acromegaly have a two- to three-fold increased risk of death. Biochemical control of the disease, as measured by both GH and IGF-1 levels, is the primary goal of treatment. Other disease-management objectives include tumor shrinkage and improvement in clinical signs and symptoms.

The pivotal phase III trial was a randomized, double-blind study comparing pasireotide LAR 40 mg or 60 mg with continued open-label treatment with octreotide LAR 30 mg or lanreotide autogel 120 mg (the control group) for 24 weeks. The trial included 198 patients with inadequately controlled acromegaly on maximal approved doses of octreotide LAR or lanreotide autogel for at least 6 months, regardless of prior surgical status. The study’s primary endpoint was the proportion of patients achieving biochemical control, as measured by mean GH levels of less than 2.5 mcg/L and normalized IGF-1 at 24 weeks.

In this study, significantly more patients achieved biochemical control with each dose of pasireotide LAR compared with the octreotide LAR and lanreotide autogel control arm. Specifically, 15.4% (P = 0.0006) and 20.0% (P < 0.0001) of those with inadequately controlled acromegaly taking pasireotide LAR 40 mg and 60 mg, respectively, achieved biochemical control versus 0% achieving biochemical control during continued treatment with octreotide LAR or lanreotide autogel.

IGF-1 normalization was achieved by 24.6% and 26.2% (both P < 0.001) of patients treated with pasireotide LAR 40 mg and 60 mg, respectively, and was not achieved by any patients in the control arm. In addition, 35.4% and 43.1% of patients in the pasireotide LAR 40 mg and 60 mg arms, respectively, had mean GH levels of less than 2.5 mcg/L compared with 13.2% in the control arm.

Tumor size was also evaluated. The study found that a greater proportion of patients treated with pasireotide LAR 40 mg and 60 mg (18.5% and 10.8%, respectively) achieved a greater than 25% decrease in tumor size compared with those receiving octreotide LAR and lanreotide autogel (1.5%).

The most common adverse events associated with pasireotide LAR 40 mg or 60 mg and the control arm were hyperglycemia (33.3%, 30.6%, and 13.6%, respectively), diabetes mellitus (20.6%, 25.8%, and 7.6%), and diarrhea (15.9%, 19.4%, and 4.5%).

In the U.S., pasireotide is approved for the treatment of adult patients with Cushing's disease for whom pituitary surgery is not an option or has not been curative.

Pasireotide LAR is an investigational multireceptor agent that binds with high affinity to four of the five somatostatin receptor subtypes (sst 1, 2, 3, and 5). As an investigational agent, the safety and efficacy profile of pasireotide LAR has not been established in acromegaly or any other indication. The formulation and dosage of pasireotide LAR when used for studying the acromegaly patient population are different from those of subcutaneous pasireotide in the approved Cushing’s disease indication.

Source: Novartis; May 5, 2014.

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