Crinetics Submits Paltusotine NDA for Acromegaly Treatment

On September 26, 2024, Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) declared the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for paltusotine. This drug is notable for being the first once-daily, orally administered, selectively-targeted somatostatin receptor type 2 nonpeptide agonist aimed at treating and providing long-term maintenance therapy for acromegaly.

Scott Struthers, Ph.D., the Founder and CEO of Crinetics, expressed enthusiasm about this milestone, emphasizing that it brings the company closer to offering a groundbreaking therapy to those living with acromegaly. The NDA submission is based on extensive data from the Phase 3 PATHFNDR program, which underscores the potential this drug holds not only for the acromegaly community but also for Crinetics as a pioneering pharmaceutical company. Paltusotine represents the forefront of an innovative pipeline, the first of many therapeutic candidates meticulously designed in-house to revolutionize the treatment of various endocrine conditions.

The NDA is underpinned by data from 18 clinical trials, including two critical Phase 3 trials that investigated paltusotine's efficacy in both untreated and previously treated acromegaly patients. The primary and secondary endpoints were successfully achieved in both studies. Paltusotine was well-tolerated, providing biochemical control and symptom management that outperformed the placebo.

Crinetics expects to receive feedback from the FDA regarding the NDA submission status by December. Paltusotine stands out as Crinetics' leading development candidate, being the first investigational, once-daily, oral, selectively-targeted somatostatin receptor type 2 (SST2) nonpeptide agonist that has completed Phase 3 clinical trials for acromegaly. It is also undergoing Phase 2 clinical trials for carcinoid syndrome associated with neuroendocrine tumors. Designed by Crinetics, paltusotine aims to offer a reliable, consistent, once-daily oral treatment for acromegaly.

Phase 3 studies have shown that paltusotine maintains IGF-1 levels and symptom control in patients transitioning from monthly injectable medications (PATHFNDR-1) and significantly reduces IGF-1 levels and symptom burden in untreated acromegaly patients (PATHFNDR-2). IGF-1 is a critical biomarker used by endocrinologists to manage acromegaly patients. The results from Phase 2 studies in carcinoid syndrome could pave the way for a Phase 3 trial to investigate its efficacy further in this area, potentially offering new treatment avenues for patients with neuroendocrine tumors.

Acromegaly is a serious, rare disease often caused by a benign tumor in the pituitary gland, leading to excessive growth hormone (GH) secretion and consequently high levels of insulin-like growth factor-1 (IGF-1) from the liver. Prolonged exposure to elevated IGF-1 and GH levels can result in severe systemic complications, including bone, joint, cardiovascular, metabolic, cerebrovascular, and respiratory diseases. Symptoms of acromegaly include headaches, joint pain, fatigue, sleep apnea, severe sweating, oily skin, bone and cartilage overgrowth, abnormal enlargement of hands and feet, and changes in facial features. If left uncontrolled, acromegaly can lead to increased mortality and significantly impact daily functioning and quality of life.

Surgical removal of pituitary adenomas is generally the preferred initial treatment for most acromegaly patients. However, for those who are not candidates for surgery or when surgery is unsuccessful, pharmacotherapy is the next step. About 50% of acromegaly patients qualify for pharmacotherapy, with injectable somatostatin receptor ligands being the most common initial treatment. These injections, however, can be painful and are associated with various side effects, impacting patients' quality of life.

Crinetics Pharmaceuticals is dedicated to the discovery, development, and commercialization of novel therapeutics for endocrine diseases and related tumors. Their lead development candidate, paltusotine, has successfully completed Phase 3 clinical trials for acromegaly and is in Phase 2 for carcinoid syndrome. Additionally, Crinetics is developing atumelnant (CRN04894), an oral ACTH antagonist, currently in Phase 2 clinical studies for congenital adrenal hyperplasia and Cushing’s disease. All of Crinetics' drug candidates are orally administered, small molecule new chemical entities resulting from their in-house drug discovery efforts, targeting a variety of endocrine conditions.