FDA Approves Paltusotine (Palsonify) As First Once-Daily, Oral Acromegaly Treatment

Crinetics Pharmaceuticals has announced the US Food and Drug Administration (FDA) approval of paltusotine (Palsonify) for the first-line treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option.1

According to a September 25, 2025, release from Crinetics, paltusotine is now the first once-daily, oral treatment approved for adults with acromegaly. The approval is based on data from the phase 3 PATHFNDR-1 and PATHFNDR-2 trials, which evaluated [paltusotine]’s safety and efficacy in previously treated and medically untreated adults with acromegaly. Across both trials, paltusotine consistently demonstrated rapid onset, reliable biochemical control, and sustained efficacy.1

“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 a statement.1 “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.”

An oral, once-daily selectively targeted somatostatin receptor type 2 (SST2) agonist, paltusotine was designed by the Crinetics discovery team to provide an efficacious and convenient once-daily option for people living with acromegaly and neuroendocrine tumors.1

The PATHFNDR program consists of 2 phase 3 double-blind, placebo-controlled studies. PATHFNDR-1 enrolled 58 adults with acromegaly who entered with an IGF-1 level ≤ 1.0x ULN on octreotide or lanreotide depot monotherapy. They were randomly assigned to receive once-daily, oral paltusotine for 36 weeks or placebo. PATHFNDR-2 enrolled 112 adults with acromegaly who had elevated IGF-1 levels but were medication naïve or were not being treated with pharmacotherapy (untreated patients). The primary endpoint for both studies was the proportion of patients achieving IGF-1 ≤1.0 xULN compared to placebo.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,” said Shlomo Melmed, MD, Executive Vice President of Medicine and Health Sciences and Dean of the Medical Faculty at Cedars-Sinai.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.”

In September 2023, Crintetics announced paltusotine met the primary endpoint and all secondary endpoints in the PATHFNDR-1 study. The study met statistical significance (P <.0001) on the primary endpoint, based on the proportion of participants taking paltusotine (83%) who maintained an insulin-like growth factor 1 (IGF-1) level ≤ 1.0 times the ULN compared to those taking placebo (4%). All secondary endpoints also met statistical significance.1,2

In addition to demonstrating rapid onset, reliable biochemical control, and sustained efficacy across both PATHFNDR-1 and PATHFNDR-2, participants in both trials also reported significant reductions in signs and symptoms associated with acromegaly as measured by the Acromegaly Symptom Diary (ASD) — an FDA-aligned patient-reported outcome tool developed to capture the symptoms that matter to people living with acromegaly. Symptoms include headaches, joint pain, sweating, fatigue, weakness, swelling, and/or numbness/tingling. Paltusotine was generally well-tolerated, with no serious adverse events reported in the randomized controlled portion of the trial.1

Long-term results from the open-label extension phases of both trials were presented at the 2025 Endocrine Society’s annual meeting, providing further evidence of paltusotine’s ability to deliver durable IGF-1 control, sustained improvements in patient symptom burden, and a consistent safety profile. In total 91% percent of patients from PATHFNDR-1 and 97% of completers from PATHFNDR-2 enrolled in the open-label extension.1

According to the release from Crinetics, paltusotine is expected to be available in the US in early October. It is also being evaluated for the treatment of carcinoid syndrome in the phase 3 CAREFNDR trial, with global enrollment expected throughout 2025.1

References

1. Crinetics. Crinetics Announces FDA Approval of PALSONIFY™ (paltusotine) for the Treatment of Acromegaly in Adults. 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. Crinetics. 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. September 10, 2023. Accessed September 26, 2025. https://crinetics.com/crinetics-paltusotine-achieved-primary-and-secondary-endpoints-in-phase-3-pathfndr-1-acromegaly-study/#:~:text=Paltusotine%20is%20an%20important%20lead,preliminary%20results%20later%20this%20year