Positive Results in Trials of First Oral Investigational Drug for Acromegaly

Alan Krasner, MD, Chief Endocrinologist at Crinetics Pharmaceuticals, discusses a series of trials testing the safety and efficacy of investigational drug paltusotine for the treatment of acromegaly.
Acromegaly is a rare endocrine disorder resulting from the overproduction of growth hormone (GH) in the pituitary gland. The condition is usually caused by benign tumors on the pituitary called adenomas. Rarely, it is caused by tumors of the pancreas, lungs, and other parts of the brain stimulating the pituitary gland to produce GH. It is most often diagnosed in middle-aged adults, although symptoms can appear at any age. Signs and symptoms include:
- Abnormal growth and swelling of the hands and feet
- Bone changes that alter various facial features
- Arthritis
- Carpal tunnel syndrome
- Enlargement of body organs
When GH-producing tumors occur in childhood, the disease that results is called gigantism rather than acromegaly. Acromegaly may also be part of other genetic syndromes such as multiple endocrine neoplasia syndrome type 1 and type 4, hereditary paraganglioma-pheochromocytoma syndrome, McCune-Albright syndrome, neurofibromatosis or Carney complex.
Current treatment for patients with acromegaly include somatostatin peptide analogs involving painful monthly or daily injections. These treatments often underperform in controlling the underlying disease. Paltusotine is the first oral, once-daily, selectively targeted somatostatin receptor type 2 (SST2) agonist in development for treatment of acromegaly, along with carcinoid syndrome.
The PATHFNDR-1 randomized, placebo-controlled, phase 3 study tested the safety and efficacy of paltusotine in patients with acromegaly who had achieved biochemical control with octreotide or lanreotide injections and were switched to oral paltusotine. Results observed included the maintaining of biochemical symptom control after patients had switched and no serious adverse effects.
The PATHFNDR-2 randomized, double-blind, placebo-controlled study tested paltusotine in untreated patients with acromegaly. Researchers observed rapid and sustained response to paltusotine with no new safety signals, maintaining that paltusotine is well tolerated.
Finally, ACROBAT Advance is an ongoing, 6-year, single-arm, open-label extension study of paltusotine in patients with acreomegaly. Interim results were presented at ENDO 2024 observing that paltusotine has been well tolerated and stable biochemical and symptom control.
Chapters:
Acromegaly Overview 00:00
Current Management 1:32
Clinical Trials 2:58
Plan for New Drug Application 6:19