2-Year Paltusotine Data Confirms Efficacy, Safety for Acromegaly in Treatment-Naïve and SRL-Treated Patients

Paltusotine is effective and well-tolerated after 2 years in both untreated patients and those switched from injectable monthly somatostatin receptor ligands (SRLs) with acromegaly, based on new data from the PATHFNDR-1 and PATHFNDR-2 trials.1,2

Presented at the Endocrine Society (ENDO) Annual Meeting 2026 in Chicago, Illinois, by Christian Strasburger, MD, senior professor of clinical endocrinology at Campus Charité Mitte in Berlin, Germany, these data represent a pooled pair of open-label extension trials. PATHFNDER-1 and PATHFNDR-2 both examined paltusotine, a selectively targeted somatosatin receptor type 2 (SST2) nonpeptide agonist, for acromegaly.1,2

“These studies indicate that Palsonify is well tolerated and maintains control of all three aspects of disease control with long-term follow-up,” Alan Krasner, MD, chief endocrinologist at Crinetics, said in a statement. “Since its launch late last year, we are learning that Palsonify is already making a meaningful difference in the lives of many people with acromegaly, and we hope these data will be helpful for patients and for their health care providers.”2

The first trial, PATHFNDR-1, was a randomized, placebo-controlled study evaluating patients who had previously received treatment with SRLs. Conducted across 39 locations worldwide, the trial excluded patients who were treatment naïve or treatment-withdrawn, had received prior paltusotine treatment, or who had undergone pituitary surgery within 24 weeks before screening, among other criteria.3

The study’s initial endpoint was the percentage of patients who maintained biochemical response in insulin-like growth factor-1 (IGF-1) by 36 weeks. Secondary endpoints included change from baseline in IGF-1 and in acromegaly symptoms. After this 36-week period, 53 of 57 patients entered the ongoing single-arm open-label extension trial. Baseline mean IGF-1 in these participants was 0.91x Upper Limit of Normal (ULN), with these levels remaining stable at both 48 and 96 weeks, at 0.82x ULN and 0.81, respectively. Symptoms remained stable from baseline at assessed timepoints, and pituitary tumor volumes were stable in patients at week 48 compared to baseline.2,3

PATHFNDR-2 was a randomized, placebo-controlled, multicenter study examining paltusotine’s efficacy in patients who had received no pharmacological treatment. The study included patients who were medically naïve, not currently treated, or willing to washout during the study. Patients were excluded if they’d undergone pituitary radiation therapy within 3 years of screening, prior treatment with paltusotine, or a history of ineffective or intolerance to octreotide or lancreotide, among other criteria.4

PATHFNDR-2’s initial primary endpoint was the percentage of patients with a biochemical response in IGF-1 at the end of the randomized control phase. Secondary outcomes included change in IGF-1 from baseline, the percentage of participants with growth hormone concentration <1 ng/mL at week 22, and change from baseline in total acromegaly symptoms.4

A total of 114 patients continued to the open-label extension – among them, baseline mean IGF-1 levels was 1.64x ULN. These levels decreased from baseline at both 48 and 72 weeks, reaching 1.06x ULN and 0.96x ULN, respectively. Pituitary tumor volume was also reduced by >20% in 7 of 83 patients with available MRI scans at week 24.2

Across both OLEs, median ASD scores were stable at each assessed timepoint. Symptoms remained stable from baseline at assessed endpoints, and no new safety signals were found. The most common adverse events were diarrhea (15.6%), arthralgia (11.4%), headache (11.4%), and urinary tract infection (10.2%). A total of 4 patients discontinued from an open-label extension due to adverse events.2

References

1. Gadelha M, Casagrande A, Strasburger C, et al. Efficacy and Safety of Once-Daily Oral Paltusotine in Patients with Acromegaly: Up to 2 Years in the PATHFNDR-1 and PATHFNDR-2 Open-Label Extension Studies. Abstract presented at the Endocrine Society (ENDO) Annual Meeting 2026, Chicago, IL. June 13-15, 2026.

2. Crinetics Pharmaceuticals. Crinetics Presents Long-Term Data at ENDO 2026 Confirming Palsonify (Paltusotine) Provides Durable, Consistent Acromegaly Control. June 14, 2026. Accessed June 18, 2026. https://ir.crinetics.com/news/news-details/2026/Crinetics-Presents-Long-Term-Data-at-ENDO-2026-Confirming-PALSONIFY-paltusotine-Provides-Durable-Consistent-Acromegaly-Control/default.aspx

3. Crinetics Pharmaceuticals. A Study to Evaluate the Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (PATHFNDR-1). ClinicalTrials.gov Identifier: NCT04837040. Updated May 15, 2026. Accessed June 18, 2026. https://clinicaltrials.gov/study/NCT04837040

4. Crinetics Pharmaceuticals. A Study to Evaluate the Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (PATHFNDR-2). ClinicalTrials.gov Identifier: NCT05192382. Updated May 15, 2026. Accessed June 18, 2026. https://clinicaltrials.gov/study/NCT05192382