FDA Accepts NDA for Paltusotine to Treat Adult Patients With Acromegaly

Updated Monday, December 9 at 11:22 AM EST.

The FDA has accepted a new drug application (NDA) for paltusotine (Crinetics Pharmaceuticals), an investigational candidate for the treatment and long-term maintenance therapy of adult patients with acromegaly.¹ The NDA submission included positive safety and efficacy data from the PATHFNDR-1 (NCT04837040)² and PATHFNDR-2 (NCT05192382)³ phase 3 clinical trials, which assessed paltusotine in previously treated and medically untreated adult patients with acromegaly.⁴

Acromegaly is a rare disease that is often caused by a benign pituitary adenoma, or a tumor, that secretes excess growth hormone (GH). The GH can also cause excess secretion of insulin-like growth factor-1 (IGF-1) from the liver. Prolonged exposure to increased levels of both IGF-1 and GH can lead to serious, progressive systemic complications, which can result in bone, joint, cardiovascular, metabolic, cerebrovascular, or respiratory disease. Symptoms of acromegaly can range, with mild symptoms including headache, joint aches, fatigue, sleep apnea, severe sweating, and hyperhidrosis or oily skin, whereas severe symptoms can include bone and cartilage overgrowth; abnormal growth of hands and feet; enlargement of heart, liver, and other organs; and alteration of facial features.¹

If approved by the FDA, the treatment will be the first and only once-daily, oral selective somatostatin receptor type 2 nonpeptide agonist available for patients who have acromegaly. It was specifically designed to be a once-daily oral option for the control of acromegaly and carcinoid syndrome-related symptoms. It was previously granted an orphan drug designation by the FDA for the treatment of acromegaly in July 2020. Additionally, the FDA set a Prescription Drug user Fee target action date of September 25, 2025.¹

THE PATHFNDR trials were 2 randomized, double-blind, placebo-controlled phase 3 trials to evaluate the safety and efficacy of paltusotine in patients with acromegaly who were either previously treated with somatostatin receptor ligand-based regimens (PATHFNDR-1)² or were not pharmacologically treated (PATHFNDR-2).³ The PATHFINDR trials enrolled 58 patients for a 36-week duration (PATHFNDR-1) and 111 patients for a 24-week duration (PATHFNDR-2).^2-4

Both trials shared the same primary outcome measure, which was the proportion of patients who maintain a biochemical response in IGF-1 at the end of the randomized control phase. Secondary outcome measures of PATHFINDR-1 included change from baseline in IGF-1, proportion of patients with GH under 1.0 mg/mL, and changes in total Acromegaly Symptoms Diary (ASD) symptom score. Additionally, PATHFINDR-2 had the same secondary outcome measures in addition to proportion of patients with IGF-1 less than 1.3 times the upper limit of normal (xULN).^2,3

According to analysis results for PATHFINDR-2⁴, the study met statistical significance based on the primary end point, which showed that approximately 56% of patients (n = 30 of 54) treated with paltusotine achieved an IGF-1 level equal to or less than 1.0 x ULN compared with about 5% of patients who received placebo (n = 3 of 57). All secondary end points were also observed to be statistically significant. Further, paltusotine was generally well-tolerated and no serious adverse events (AEs) were reported by participants treated with paltusotine. The most reported treatment-emergent AEs in paltusotine-treated participants included diarrhea, headache, arthralgia, and abdominal pain. The investigators also observed that the frequency of AEs considered acromegaly-related was noticeably lower in participants treated with paltusotine compared with placebo.⁴

“With our patient-centered clinical development of paltusotine, we were guided by an unwavering ambition to deliver a new generation of treatment that provides a once-daily, oral alternative to the currently marketed peptide analog drugs,” said Scott Struthers, PhD, founder and CEO of Crinetics Pharmaceuticals, in a news release. “We look forward to working with the FDA throughout the review of our new drug application…”¹

REFERENCES

1. GlobeNewswire. Crinetics Announces FDA Acceptance of New Drug Application for Paltusotine for Adult Patients with Acromegaly. News release. December 9, 2024. Accessed Decmeber 9, 2024. https://www.globenewswire.com/news-release/2024/12/09/2993693/0/en/Crinetics-Announces-FDA-Acceptance-of-New-Drug-Application-for-Paltusotine-for-Adult-Patients-with-Acromegaly.html

2. A Study to Evaluate the Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (PATHFNDR-1). ClinicalTrials.gov identifier: NCT04837040. Updated July 10, 2024. https://clinicaltrials.gov/study/NCT04837040

3. A Study to Evaluate the Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (PATHFNDR-2) (PATHFNDR-2). ClinicalTrials.gov identifier: NCT05192382. Updated March 29, 2024. Accessed December 9, 2024. https://clinicaltrials.gov/study/NCT05192382

4. Crinetics Pharmaceuticals. Crinetics’ Once-Daily Oral Paltusotine Achieved the Primary and All Secondary Endpoints in the Phase 3 PATHFNDR-2 Study in Acromegaly Patients. News release. March 19, 2024. Accessed December 9, 2024. https://crinetics.com/crinetics-once-daily-oral-paltusotine-achieved-the-primary-and-all-secondary-endpoints-in-the-phase-3-pathfndr-2-study-in-acromegaly-patients/