Crinetics Reports Positive Results from Phase 3 Study of Paltusotine in Acromegaly

Rare Daily Staff

Crinetics Pharmaceuticals reported experimental therapy paltusotine met the primary and all secondary endpoints in the phase 3 PATHFNDR-2 study in people with acromegaly.

Acromegaly is a serious rare disease generally caused by a pituitary adenoma, a benign tumor in the pituitary that secretes growth hormone (GH). Excess GH secretion causes excess secretion of IGF-1 from the liver. Prolonged exposure to increased levels of IGF-1 and GH leads to progressive and serious systemic complications, often resulting in bone, joint, cardiovascular, metabolic, cerebrovascular, or respiratory disease. Acromegaly symptoms include headache, joint aches, fatigue, sleep apnea, severe sweating, hyperhidrosis/oily skin, bone and cartilage overgrowth, abnormal growth of hands and feet, enlargement of heart, liver, and other organs and alteration of facial features. Uncontrolled acromegaly results in increased mortality and has a debilitating impact on daily functioning and quality of life.

Though surgical removal of pituitary adenomas is the preferred initial treatment, approximately 50 percent of patients with acromegaly prove to be candidates for pharmacotherapy. Injectable depot somatostatin analogues are the most common initial pharmacologic treatment; however, these drugs require monthly depot injections with large gauge needles that are commonly associated with pain, injection site reactions, and an increased burden on the lives of patients.

Paltusotine is the first oral, once-daily selectively-targeted somatostatin receptor type 2 (SST2) agonist that was designed to provide an efficacious and convenient once-daily option for people living with acromegaly and carcinoid syndrome. In phase 2 studies and the recently completed PATHFNDR-1 phase 3 study, paltusotine maintained IGF-1 levels in acromegaly patients who switched from monthly injectable medications to paltusotine. IGF-1 is the primary biomarker endocrinologists use to manage acromegaly patients.

PATHFNDR-2 was a randomized, double-blind, placebo-controlled 24-week treatment period followed by an optional open-label extension study evaluating paltusotine in 111 participants with acromegaly who were not pharmacologically treated. The study met statistical significance on the primary endpoint, based on the proportion of participants taking paltusotine (56 percent) who achieved an insulin-like growth factor 1 (IGF-1) level ≤ 1.0 times the upper limit of normal compared to those taking placebo (5 percent). All secondary endpoints also met statistical significance. Paltusotine was generally well-tolerated and no serious adverse events were reported.

“Building upon the success of PATHFNDR-1, the totality of data underscores the potential of paltusotine to provide an important new treatment option for all people living with acromegaly, if approved,” said Scott Struthers, founder and CEO of Crinetics.

The company intends to submit a New Drug Application to the U.S. Food and Drug Administration in the second half of 2024, and is actively preparing for a potential 2025 launch.

Photo: Scott Struthers, founder and CEO of Crinetics