Novartis has announced the results of the largest phase III study of acromegaly patients show the novel therapy pasireotide (SOM230) long-acting release (LAR), was significantly more effective at inducing full biochemical control compared to the current standard medical therapy, Sandostatin LAR (octreotide/IM injection).

These data were presented at the 2012 joint 15th International Congress of Endocrinology and 14th European Congress of Endocrinology meeting (ICE/ECE) in Florence, Italy.

Acromegaly is a rare endocrine disorder characterized by enlargement of the hands, feet and internal organs, as well as changes in facial structure. The majority of acromegaly cases are caused by a non-cancerous tumour in the pituitary gland that secretes excess growth hormone (GH), leading to elevated levels of insulin like growth factor (IGF-1).

The study met its primary endpoint, with significantly more patients treated with pasireotide LAR (31.3 per cent) experiencing full control of their disease (defined as the combination of both GH <2.5µg/L and age- and sex-matched normalized IGF-1 levels) than those taking octreotide LAR (19.2 per cent) (p=0.007). Patients treated with pasireotide LAR were 63 per cent more likely to achieve control of their disease than those on octreotide LAR. The safety profile of pasireotide LAR was similar to that of octreotide LAR with the exception of a higher degree of hyperglycaemia.

Growth hormone and IGF-1 levels are typically used to determine control of the disease with the most commonly used standard medical therapy, somatostatin analogues. Currently, only 20-25 per cent of acromegaly patients naïve to previous somatostatin analogue treatment achieve full control over their disease when treated with current somatostatin analogues, as measured by these two levels.

“While Sandostatin LAR is an effective treatment, inadequate control of GH and IGF-1 remains an issue for many patients with acromegaly and new therapeutic approaches are needed for these patients to better control their disease,” said Annamaria Colao, MD, lead study investigator and Professor of Endocrinology, Chief of the Neuroendocrine Unit at the Department of Molecular and Clinical Endocrinology and Oncology, Federico II University of Naples. “We are very encouraged by the findings of this study, the largest ever in this population, which found that pasireotide LAR provided full control in nearly a third of study participants.”

Investigators also presented data from a 6-month extension study, where paftients who did not achieve full biochemical control after 12 months on therapy could switch to the other treatment. After an additional 6 months of treatment, 21 per cent of the 81 patients who switched to pasireotide LAR achieved full control of their disease. By contrast, of the 38 patients who switched to octreotide LAR, 2.6 per cent achieved full control.

“The positive results seen in the phase III trial point to the potential role of pasireotide LAR in treating patients with acromegaly, a condition for which there remains an unmet need,” said Hervé Hoppenot, president, Novartis Oncology. “These findings are welcome news as we continue our research efforts to discover treatments for patients with pituitary-related conditions.”

In addition to acromegaly, Novartis is committed to studying other pituitary-related conditions including continued study in Cushing's disease. Data also presented at this meeting include long-term follow-up results from the phase III registrational trial which led to the recent EU approval of Signifor (pasireotide) for the treatment of Cushing's disease. Additionally, researchers presented data from a phase I proof-of-concept trial for the investigational 11&beta;-hydroxylase inhibitor, LCI699, in Cushing's disease.

Acromegaly is a chronic hormonal disorder that occurs when excess growth hormone is produced. Commonly, acromegaly presents in middle-aged men and women and can result in changes in metabolism and an increased risk of mortality. People with acromegaly may also suffer from changes to facial structure, such as enlargement of forehead and jaw with pronounced under- or overbite, spreading teeth and enlarged tongue. More serious problems may include accelerated cardiovascular disease, hypertension, diabetes mellitus and possibly an increased risk of colon cancer.

Pasireotide (SOM230) is an investigational multireceptor targeting somatostatin analog (SSA) that binds with high affinity to four of the five somatostatin receptor subtypes (sst 1, 2, 3 and 5). Pasireotide is approved in the EU as Signifor for the treatment of adult patients with Cushing's disease for whom surgery is not an option or for whom surgery has failed. Additional regulatory submissions for pasireotide for the treatment of Cushing's disease are under way worldwide.

Sandostatin LAR is a long-acting, injectable depot formulation of octreotide acetate that is indicated for the treatment of patients who are adequately controlled on s.c. treatment with Sandostatin; in patients in whom surgery or radiotherapy is inappropriate or ineffective; in the interim period until radiotherapy becomes fully effective. Treatment of patients with symptoms associated with functional gastro-entero-pancreatic endocrine tumours: carcinoid tumours with features of the carcinoid syndrome, VIPomas, glucagonomas, gastrinomas/Zollinger-Ellison syndrome, insulinomas, GRFomas. Treatment of patients with advanced neuroendocrine tumours of the midgut or unknown primary tumour location.

Sandostatin LAR was first approved in France in June 1995 and is currently approved in 95 countries. For more than a decade, Sandostatin LAR has achieved a long-standing track record of sustained efficacy with a well-established safety profile.