Acromegaly

It is a life threatening condition where increased mortality is associated with the failure to normalise insulin-like growth factor-1 (IGF-1) and GH. Acromegaly is a rare disorder with 80,000 patients worldwide although recent evidence shows that prevalence is increasing. The “hypersecretory" nature of Acromegaly makes it an ideal target for Syntaxin’s TSI technology platform.

Aetiology

The most common cause of Acromegaly is a somatotrophic adenoma (a growth hormone-secreting tumour) of the anterior pituitary gland. Proliferation of the somatotroph results in oversecretion of growth hormone which in turn triggers release of IGF-1 from the liver. These hypersecretions form the basis of diagnosis of the disease, which is both rare and has a high unmet medical need.

The annual incidence of Acromegaly is 2.8-3.3 per million population (900 new cases per year in the USA) and a prevalence of 38-69 per million (20,000 cases in the USA). MRI imaging is able to show the size and location of the tumour, with microadenomas being the most amenable to surgical resection through the transsphenoidal route.

Medical Need

The clinical features of Acromegaly are tissue enlargement (frontal bossing, protruding jaw, enlarged hands and feet), early onset arthritis, with metabolic complications (respiratory, cardiovascular and diabetes) contributing to the increased risk of mortality.

There is a significant medical need for a novel safe and effective therapeutic which can normalise IGF in Acromegalic patients. First line treatment is by surgical resection of the causative somatotrophic adenoma. Relapse following surgery is common (30-40%) and the patient then requires therapeutic intervention, usually with one of the longer acting somatostatinagonists octreotide (Sandostatin® LAR) or lanreotide (Somatuline® LA). Complete normalisation of patient’s hormone levels is not achieved in about 60% of cases. Other therapies are then considered, such as Somavert® (blocking the growth hormone receptor) or use of dopamine agonists such as bromocriptine. In addition to their lack of efficacy, current treatments have side effects and adverse reactions: somatostatin analogues for example are associated with gall stones, diabetes, bradycardia and abdominal pain while abnormal liver function tests are seen in 4% of patients treated with GH receptor antagonists.

Product Profile

Syntaxin’s approach aims to address the need for both a safer and more efficacious product that directly targets the source of the endocrine abnormality, the somatotroph. This aims to bring benefit to patients through a long acting therapy that will improve compliance and convenience. Syntaxin believes its novel TSI has the potential to deliver broad benefits in this condition and to increase the flexibility of medical treatment options at several stages in the treatment hierarchy, as summarised in the following graphic.

Development Status

This product is currently in the preclinical development phase.