Paltusotine (Palsonify; Crinetics), a novel nonpeptide somatostatin receptor type 2 nonpeptide (SST2) agonist, was FDA approved for the treatment of acromegaly in adults who had an inadequate response to surgery and/or for whom surgery is not an option, according to a
The approval, which was based on data from the pivotal PATHFNDR-1 (
In PATHFNDR-1, 83% of patients maintained an insulin-like growth factor 1 (IGF-1) level of ≤1.0 times the upper limit of normal (xULN), compared with 4% of patients taking a placebo after switching from injected depot standard of care. This was the study’s primary end point, which was met with statistical significance (P < .0001).2 The study also met its secondary end points of change from baseline in IGF-1 level, change from baseline in Acromegaly Symptoms Diary (ASD) total score, and the proportion of participants who maintained a growth hormone level of <1.0 ng/mL.
PATHFNDR-2 also met its primary and secondary end points, with 56% of previously pharmacologically treated patients achieving an IGF-1 level ≤ 1.0xULN compared with 5% of those taking placebo (P < .0001).3 Secondary end points, which aligned with those in the PATHFNDR-1 study, also met statistical significance.
Updated open-label extension data from both trials presented at the ENDO 2025 meeting reinforced paltusotine’s efficacy in IGF-1 control, sustained improvements in ASD scores, and manageable safety.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, executive vice president of Medicine and Health Sciences and dean of the medical faculty at Cedars-Sinai, said in a statement.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.”
The randomized controlled portions of PATHFNDR-1 and PATHFNDR-2 reported no serious adverse events, and 91% and 97% of patients enrolled in the open-label extension portions of PATHFNDR-1 and PATHFNDR-2, respectively.
“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. “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.”
Paltusotine is expected to launch in the US in October, according to the press release.
References
1. Crinetics announces FDA approval of Palsonify (paltusotine) for the treatment of acromegaly in adults. News release. Crinetics. September 25, 2025. Accessed September 26, 2025.
2. 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. News release. Crinetics. September 10, 2023. Accessed September 26, 2025.
3. Crinetics’ once-daily oral paltusotine achieved the primary and all secondary endpoints in the phase 3 PATHFNDR-2 study in acromegaly patients. News release. Crinetics. March 19, 2024. Accessed September 26, 2025.