Novartis drug Signifor® LAR shows superior efficacy in acromegaly patients not controlled on first generation somatostatin analogues

Novartis today presented results from a pivotal Phase III trial of investigational therapy Signifor® LAR (pasireotide LAR; SOM230) in patients with acromegaly for whom current standard of care provides inadequate disease control. The study findings showed that patients taking pasireotide long-acting release (LAR) achieved greater disease control when compared to continued treatment with the standard somatostatin analogue therapies, octreotide LAR or lanreotide Autogel*. These data were presented at the 16th European Congress of Endocrinology³.

Acromegaly is caused by a benign (non-cancerous) tumor within the pituitary gland that secretes excess growth hormone (GH), leading to elevated levels of insulin-like growth factor-1 (IGF-1)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 morbidities such as cardiovascular, metabolic and respiratory diseases^1,4. If exposed to long-term elevated levels of GH and IGF-1, acromegaly patients face a two- to three-fold increased risk of death^2,5. 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 symptoms¹.

“Historically, we have evaluated somatostatin analogues for the treatment of acromegaly by the decrease in either growth hormone or insulin-like growth factor levels. With more sensitive assays and more stringent evaluation criteria, a recent meta-analysis indicates that up to 45% of patients can have either GH or IGF-I still elevated,” said Dr. Monica Gadelha, professor, Federal University of Rio de Janeiro and study author. “As the health risks associated with acromegaly may persist until both GH and IGF-1 levels are normalized, this study further supports the importance of monitoring for and achieving full biochemical control.”

This study evaluated pasireotide LAR 40 mg and 60 mg against continued therapy with octreotide LAR or lanreotide Autogel in patients who did not achieve GH and IGF-1 biochemical control despite receiving the maximum approved doses of these currently available somatostatin analogues (SSAs). In the trial, significantly more patients achieved biochemical control with each dose of pasireotide LAR compared to the octreotide LAR and lanreotide Autogel control arm. Specifically, 15.4% and 20.0% of those with inadequately controlled acromegaly taking pasireotide LAR 40 mg and 60 mg, respectively (95% confidence interval [CI], 7.6-26.5; P=0.0006; 95% CI, 11.1-31.8; P<0.0001), achieved biochemical control versus 0% achieving biochemical control on continued treatment with octreotide LAR or lanreotide Autogel (95% CI, 0-5.3). The incidence and severity of adverse events (AEs) was similar across all treatment groups, except for a higher frequency and degree of hyperglycemia in the pasireotide LAR arm³.

“These results strengthen our understanding of this rare endocrine disorder and suggest pasireotide LAR may offer benefit for acromegaly patients whose disease is not fully controlled on their current therapy,” said Alessandro Riva, president, Novartis Oncology ad interim and Global Head, Oncology Development and Medical Affairs. “As part of our long-standing commitment to transforming the care of rare pituitary diseases, we are working to bring this potentially meaningful solution to the acromegaly community.”

Worldwide regulatory filings for pasireotide LAR in acromegaly are currently underway based on these results and separate previously published robust Phase III data.

References

1. Acromegaly. National Institutes of Health. National Institute of Diabetes and Digestive and Kidney Diseases. 2008 May; 8(3924): 1-10.
2. Holdaway, et. al. A Meta-Analysis of the Effect of Lowering Serum Levels of GH and IGF-I on Mortality in Acromegaly. European Journal of Endocrinology. 2008;159:89-95
3. Gadelha M, et. al. Pasireotide LAR Demonstrates Superior Efficacy Versus Octreotide LAR and lanreotide ATG in Patients With Inadequately Controlled Acromegaly: Results From A . Phase III, Multicentre, Randomized Study. European Congress of Endocrinology. May 2014, Wroclaw, Poland.
4. Ayuk J and M C Sheppard. Growth hormone and its disorders. Post Grad Med J 2006; 82:24-30.
5. Holdaway M et al. Factors Influencing Mortality in Acromegaly. The Journal of Clinical Endocrinology & Metabolism 89(2):667-674.