Paltusotine Receives FDA Approval to Treat Acromegaly in Adults

The FDA has approved paltusotine (Palsonify; Crinetics Pharmaceuticals, Inc) for first-line treatment of adults with acromegaly who had an inadequate response to surgery or for whom surgery is not an option. This approval marks paltusotine—a somatostatin receptor agonist—as the first once-daily, oral treatment granted for this patient population, supported by data from 2 phase 3 pivotal trials, PATHFNDR-1 (NCT04837040) and PATHFNDR-2 (NCT05192382).^1-3

“With the FDA approval of our lead therapy [paltusotine], today marks a new era for those living with acromegaly and also for Crinetics as a company,” Scott Struthers, PhD, founder and chief executive officer of Crinetics, said in a news release. “We are very pleased to be fulfilling our commitment to transforming patient lives. This approval is the first to come from our deep pipeline of first-in-class, small-molecule drugs.”¹

Understanding Acromegaly

Acromegaly is a rare condition in adults that causes some bones, organs, and other tissues to grow bigger, driven by too much growth hormone in the pituitary gland, which is in the brain. Symptoms of the condition alter the way some body parts appear, including thick ears and lips, a broad nose, enlarged hands and feet, a jutting brow or jaw, gaps between teeth, an enlarged tongue, and an expanded rib cage that may cause the chest to have a round shape. Other symptoms include skin changes, such as acne, skin tags, coarse, oily, and thickened skin, and swelling in the tissue under the skin. Since these changes occur slowly, it is often difficult to identify initial symptoms, leading to a prolonged disease onset. Surgery and radiation can lower the risk of complications and could improve various acromegaly symptoms; however, without treatment, individuals could face other serious and life-threatening complications.⁴

“For people living with acromegaly, treatment once meant burdensome injections, breakthrough symptoms, and lifestyle sacrifices just to stay on track,” Jill Sisco, president of Acromegaly Community, said in the news release. “What matters most to our community—maintaining consistent control so the disease doesn’t control us—led us to partner with the FDA on Externally Led Patient-Focused Drug Development meetings. This new treatment reflects that our voices have been heard in shaping the next generation of acromegaly care.”¹

Clinical Trial Data Supporting Paltusotine

The approval for paltusotine is based on data from the phase 3 PATHFNDR-1 and PATHFNDR-2 trials, which assessed the drug’s safety and efficacy in adults with acromegaly, including those who were previously treated and those who were not.¹

In PATHFNDR-1, the study achieved statistical significance on its primary end point, showing that 83% of participants taking paltusotine maintained an insulin-like growth factor 1 (IGF-1) level at or below the upper limit of normal, compared to only 4% of those taking a placebo. All secondary end points in the study also met statistical significance.⁵

Like the initial study results, PATHFNDR-2 also achieved statistical significance on its primary end point, showing that 56% of participants taking paltusotine achieved an IGF-1 level at or below the upper limit of normal, compared to only 5% of those who received a placebo.⁶

The findings suggest that across both studies, paltusotine consistently showed a rapid onset of action, achieved reliable biochemical control, and maintained sustained efficacy. Additionally, long-term results from the open-label extension phases of both trials demonstrated further evidence of paltusotine’s ability to deliver durable IGF-1 control, sustained improvements in patient symptom burden, and a consistent safety profile.¹

“The PATHFNDR clinical development program set a new standard for acromegaly treatment by demonstrating the ability of [paltusotine] to drive both biochemical and symptom control, regardless of the degree of underlying disease severity,” Shlomo Melmed, MB, ChB, FRCP, MACP, executive vice president of medicine and health sciences and dean of the medical faculty at Cedars-Sinai, said in the news release.¹

The company noted that paltusotine is expected to be available in the US in early October, and the drug is also undergoing evaluation for the treatment of carcinoid syndrome.¹

“The approval of [paltusotine] is a significant advancement for our patients, as there is an unmet need for an easy-to-administer and safe therapeutic option with a rapid action and durable response that can consistently manage acromegaly,” Melmed concluded.¹

REFERENCES

1. Crinetics Announces FDA Approval of PALSONIFY™ (paltusotine) for the Treatment of Acromegaly in Adults. Crinetics. News release. September 25, 2025. Accessed September 26, 2025. https://crinetics.com/crinetics-announces-fda-approval-of-palsonify-paltusotine-for-the-treatment-of-acromegaly-in-adults/

2. A Study to Evaluate the Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (PATHFNDR-1). National Library of Medicine. Updated June 12, 2025. Accessed September 26, 2025. 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) National Library of Medicine. Updated June 12, 2025. Accessed September 26, 2025. https://clinicaltrials.gov/study/NCT05192382

4. Mayo Clinic. Acromegaly. News release. March 12, 2025. Accessed September 26, 2025. https://www.mayoclinic.org/diseases-conditions/acromegaly/symptoms-causes/syc-20351222

5. Crinetics’ Once-Daily Oral Paltusotine Achieved the Primary and All Secondary Endpoints in the Phase 3 PATHFNDR-1 Study Evaluating Treatment of Patients with Acromegaly. Crinetics. September 10, 2023. Accessed September 26, 2025. https://crinetics.com/crinetics-paltusotine-achieved-primary-and-secondary-endpoints-in-phase-3-pathfndr-1-acromegaly-study/

6. Crinetics’ Once-Daily Oral Paltusotine Achieved the Primary and All Secondary Endpoints in the Phase 3 PATHFNDR-2 Study in Acromegaly Patients. Crinetics. March 19, 2024. Accessed September 26, 2025. 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/