FDA Accepts Crinetics' New Drug Application for Paltusotine in Acromegaly

Crinetics Pharmaceuticals, Inc., a clinical stage pharmaceutical company based in San Diego, announced a significant milestone with the U.S. Food and Drug Administration (FDA) accepting its New Drug Application (NDA) for paltusotine. This investigational candidate is aimed at treating and maintaining therapy for acromegaly in adults. Should it receive approval, paltusotine would become the first and only once-daily, oral, selective somatostatin receptor type 2 nonpeptide agonist available for adult patients suffering from acromegaly.

Scott Struthers, Ph.D., the Founder and Chief Executive Officer of Crinetics, emphasized their dedication to providing a patient-focused approach with paltusotine. He highlighted the ambition to create a new treatment generation that offers a once-daily, oral alternative to the current peptide analog drugs on the market. The company is actively collaborating with the FDA during the review process while also laying the groundwork for a potential commercial launch by engaging with healthcare payers and the endocrinology community.

The NDA submission for paltusotine is supported by data from two Phase 3 clinical trials, PATHFNDR-1 and PATHFNDR-2, which evaluated its safety and efficacy in both previously treated and untreated adults with acromegaly. The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date for September 25, 2025, for completing the NDA review. Notably, an advisory committee meeting is not expected to be part of this process.

In July 2020, the FDA granted paltusotine Orphan Drug Designation for the treatment of acromegaly, a status provided to drugs intended for the safe and effective treatment, diagnosis, or prevention of rare diseases affecting fewer than 200,000 people in the U.S.

Crinetics' lead candidate, paltusotine, is the first investigational once-daily, oral, targeted somatostatin receptor type 2 (SST2) nonpeptide agonist to complete Phase 3 clinical trials for acromegaly. Additionally, it is beginning Phase 3 clinical development for carcinoid syndrome associated with neuroendocrine tumors. Designed as a daily oral option, paltusotine aims to control acromegaly and mitigate symptoms related to carcinoid syndrome. The Phase 3 trials indicated that paltusotine effectively maintained IGF-1 levels and symptom control in patients transitioning from monthly injectable medications and significantly reduced IGF-1 levels and symptom burden in untreated patients. The primary biomarker used by endocrinologists to manage acromegaly is IGF-1.

Acromegaly is a severe, rare disease primarily caused by a benign pituitary adenoma that secretes excess growth hormone (GH), leading to elevated levels of insulin-like growth factor-1 (IGF-1) from the liver. Prolonged exposure to high IGF-1 and GH levels can result in serious systemic complications, often affecting the bones, joints, cardiovascular system, metabolism, cerebrovascular function, and respiration. Symptoms of acromegaly include headaches, joint pain, fatigue, sleep apnea, excessive sweating, oily skin, abnormal growth of hands and feet, and enlargement of internal organs.

The most common pharmacologic treatments for acromegaly currently involve monthly depot injections of peptide somatostatin receptor ligands. However, these treatments typically take several months to achieve the correct dosage. Patients often experience symptom recurrence towards the end of their injection cycle, necessitating more frequent administration. These injections are also associated with pain, site reactions, and an increased burden on patients' lives.

Crinetics Pharmaceuticals focuses on discovering, developing, and commercializing novel therapeutics for endocrine diseases and endocrine-related tumors. Their portfolio includes paltusotine and atumelnant, an investigational, first-in-class oral ACTH antagonist for congenital adrenal hyperplasia and Cushing’s disease, currently in Phase 2 clinical studies. All their drug candidates are orally delivered, small molecule entities developed through in-house drug discovery efforts.