Veldoreotide Modified Release: A Novel Somatostatin Analogue

Granted orphan drug designation by the FDA and European Medicines Agency

Veldoreotide, or COR-005, is a preclinical next-generation somatostatin analogue (SSA) being investigated for the treatment of acromegaly and potential additional applications in other conditions amenable to somatostatin receptor activation.

First-generation SSAs bind to somatostatin receptors, inhibiting the secretion of growth hormone. However, they are also associated with undesirable inhibition of other endocrine hormones (insulin, glucagon) in locations outside the pituitary.

Veldoreotide may offer an improved safety and efficacy profile compared to other SSAs because of its differentiated activation of somatostatin receptor subtypes.

The screening of potential long-acting release (LAR) technologies for veldoreotide has been completed, and a proprietary formulation allowing subcutaneous delivery has been selected based upon PLGA microspheres for further development.

Differential Inhibition of Growth Hormone and Insulin Secretion by Immediate-Release Veldoreotide Studied

In short-term phase 1 and 2 studies in healthy volunteers and untreated patients with acromegaly, respectively, the effects of subcutaneously administered immediate-release veldoreotide on stimulated or basal growth hormone and postprandial glucose and insulin secretion were compared with those of subcutaneous injections of immediate-release octreotide. The findings suggest that veldoreotide has similar ability as octreotide to suppress growth hormone but has reduced propensity to inhibit postprandial insulin.1,2

Based on the differentiated activation pattern of somatostatin receptor subtypes (SSTs) and the preclinical and clinical profile of immediate-release veldoreotide, we believe that modified-release veldoreotide is a next-generation somatostatin analogue with potential applications in endocrine and non-endocrine conditions that are amenable to somatostatin receptor activation.

No serious adverse events were observed, and mostly mild adverse events typical for SSAs such as injection site reactions and gastrointestinal side effects were reported. There was no evidence that veldoreotide adversely affects the liver, kidneys, or other organ systems, including the cardiovascular system.

The safety and efficacy of veldoreotide for treatment of acromegaly have not been established.

References

  1. Data from phase 1 single-blind placebo-controlled multiple ascending dose study in 42 healthy male subjects given 300 µg octreotide or COR-005 100-1800 µg tid sc over 6 days.
  2. Data from a phase 2 open-label, single ascending dose study in 20 subjects with acromegaly, fixed-dose sequence with 1 week wash-out between treatments of 300 µg sc octreotide, followed by COR-005 100–1800 µg sc, under fasting conditions.