Data from up to two years of treatment in PATHFNDR-1 and PATHFNDR-2 open-label extension studies show PALSONIFY maintained lower IGF-1 levels and stable symptoms
Treatment also resulted in stable or reduced pituitary tumor volumes for up to 48 weeks
Additional ENDO highlights include long-term ACROBAT data demonstrating PALSONIFY and cabergoline combination improves biochemical control of acromegaly
SAN DIEGO, June 14, 2026 (GLOBE NEWSWIRE) -- Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) today announced new long-term data from its clinical development program evaluating novel PALSONIFYTM (paltusotine) in acromegaly during an oral presentation at the Endocrine Society’s Annual Meeting, ENDO 2026. Notably, pooled data from the open-label extension (OLE) trials of PATHFNDR-1 and PATHFNDR-2 show that after two years of treatment, PALSONIFY was effective and well-tolerated in patients who were switched from standard-of-care monthly injectable somatostatin receptor ligands (SRLs) and those who were medically untreated, respectively, when oral, once-daily PALSONIFY was initiated.
“To assess acromegaly disease control while on medication, endocrinologists carefully monitor control of IGF-1 levels, control of acromegaly symptoms, and stabilization of pituitary tumors,” said Dr. Alan Krasner, M.D., Chief Endocrinologist, Crinetics. “At this year’s ENDO meeting, long-term safety and efficacy data from the PATHFNDR OLE trials will be presented. These studies indicate that Palsonify is well tolerated and maintains control of all three aspects of disease control with long-term follow-up. 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.”
Pooled OLE Efficacy and Safety Results
PATHFNDR-1 Data
The PATHFNDR-1 Phase 3 trial enrolled adults with acromegaly who were biochemically controlled on monthly injectable SRLs. Following a 36-week randomized, placebo-controlled period, 53 of 57 participants (93%) entered the ongoing single-arm open-label extension (OLE) trial.
Baseline mean IGF-1 levels for OLE participants (n=53) was 0.91x Upper Limit of Normal (ULN). These levels remained stable at both 48 weeks (n=50) and 96 weeks (n=47) of the study: 0.82x ULN and 0.81, respectively. Symptoms associated with acromegaly, as measured by the Acromegaly Symptom Diary (ASD), remained stable from baseline at assessed timepoints. Additionally, pituitary tumor volumes were reported as stable in all patients at week 48, relative to OLE baseline.
PATHFNDR-2 Data
The PATHFNDR-2 trial evaluated once-daily oral PALSONIFY in adults with biochemically uncontrolled acromegaly (baseline IGF-1 > 1.3 × ULN). After a 24-week randomized controlled (RC period, 103 of 106 completers (97.2%) entered the ongoing OLE, along with 11 additional patients who were eligible for the RC phase but enrolled directly into the OLE.
Baseline mean IGF-1 levels for OLE participants (n=114) was 1.64×ULN. These levels decreased from baseline at both 48 weeks (n=98) and 72 weeks (n=78) of the study: 1.06×ULN and 0.96×ULN, respectively.
Relative to OLE baseline, pituitary tumor volume was reduced by >20% in 7 of 83 PATHFNDR-2 patients with available MRI scans at OLE Week 24. Tumor volume was reported as stable in the other 76 participants.
In both OLEs, median ASD scores were stable at the timepoints assessed. Symptoms associated with acromegaly, as measured by the Acromegaly Symptom Diary (ASD), remained stable from baseline at assessed timepoints.
No new safety signals were found. In the pooled OLE population (n=167), the most common adverse events (incidence>10%) were diarrhea (15.6%), arthralgia (11.4%), headache (11.4%), and urinary tract infection (10.2%). Four patients (2.4%) discontinued from an OLE due to adverse events as of this analysis.
These results were included in an oral presentation at ENDO 2026 titled “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.”
Additionally, an analysis was presented at ENDO 2026 that evaluated the safety and efficacy of PALSONIFY in combination with oral cabergoline in patients with acromegaly who have been followed for up to four years in ACROBAT Advance, an ongoing, single-arm, open-label extension phase 2 study. IGF-I levels on paltusotine monotherapy were similar to parent study baseline values (on injected SRL), but for those in whom IGF-1 had not yet normalized, it further improved when oral cabergoline was added. Combination therapy was well tolerated.
Crinetics’ ENDO 2026 presentations can be found at: https://crinetics.com/news-events/endo-2026/
PALSONIFY™ (paltusotine) INDICATION:
PALSONIFY is a somatostatin receptor agonist indicated for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS:
- Cholelithiasis and Its Complications: Cholelithiasis, including related complications such as acute cholecystitis and pancreatitis, have been reported. Monitor patients periodically. Discontinue PALSONIFY if complications of cholelithiasis occur and treat appropriately.
- Hyperglycemia and Hypoglycemia: Hyperglycemia, diabetes mellitus, or hypoglycemia, may occur. Monitor blood glucose levels when PALSONIFY treatment is initiated or when dosage is altered. Adjust antidiabetic treatment accordingly.
- Cardiovascular Abnormalities: Cardiac conduction abnormalities and other ECG changes such as PR interval prolongation, bradycardia, sinus arrest, and atrioventricular block may occur in patients with acromegaly and were reported in PALSONIFY clinical trials. Dosage adjustments of concomitant drugs that have bradycardic effects may be necessary.
- Thyroid Function Abnormalities: Somatostatin analogs may suppress the secretion of thyroid-stimulating hormone, which may result in hypothyroidism. Periodic assessment of thyroid function is recommended.
- Steatorrhea and Malabsorption of Dietary Fats: Somatostatin analog treatment may result in malabsorption of dietary fats and subsequent symptoms of steatorrhea, loose stools, abdominal bloating, and weight loss. If new or worsening symptoms are reported with PALSONIFY, evaluate patients for potential pancreatic exocrine insufficiency and manage accordingly.
- Vitamin B12 Deficiency: Vitamin B12 deficiency may occur. Monitor vitamin B12 levels, if clinically indicated.
ADVERSE REACTIONS:
Most common adverse reactions (>5%) are diarrhea, abdominal pain, nausea, decreased appetite, sinus bradycardia, hyperglycemia, palpitations, and gastroenteritis.
DRUG INTERACTIONS:
- Strong or Moderate CYP3A4 Inducers: may decrease PALSONIFY exposure. May require an increased dosage of PALSONIFY.
- Proton Pump Inhibitors: may decrease PALSONIFY exposure. May require an increased dosage of PALSONIFY. Avoid concomitant use of proton pump inhibitors in patients who are already on PALSONIFY 60 mg.
- Cyclosporine: may decrease cyclosporine exposure. May require cyclosporine dosage adjustment when used with PALSONIFY; follow therapeutic monitoring recommendations.
Please report adverse events to Crinetics Pharmaceuticals at 1-833-CRN-INFO (1-833-276-4636) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.ww.fda.gov/medwatch.
Please see Full Prescribing Information including Patient Information.
About PALSONIFY™ (Paltusotine)
PALSONIFY, a selectively-targeted somatostatin receptor type 2 (SST2) nonpeptide agonist, is the first and only once-daily, oral therapy approved for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. In Phase 3 studies, once-daily, oral PALSONIFY maintained IGF-1 levels and symptom control in patients with acromegaly who were switched from monthly injectable medications (PATHFNDR-1) and rapidly decreased IGF-1 levels and symptom burden in medically untreated acromegaly patients (PATHFNDR-2). IGF-1 is the primary biomarker endocrinologists use to manage acromegaly patients. Paltusotine is also in Phase 3 clinical development for carcinoid syndrome associated with neuroendocrine tumors (CAREFNDR). Results from a Phase 2 study in carcinoid syndrome demonstrated rapid and sustained reductions in flushing episodes and bowel movement frequency, which are the most common symptoms of carcinoid syndrome.
PALSONIFY is approved in the U.S. 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. It is also approved for use in the EU for the medical treatment of adult patients with acromegaly.
About Crinetics Pharmaceuticals
Crinetics Pharmaceuticals is a global pharmaceutical company committed to transforming the treatment of endocrine diseases and endocrine-related tumors through science rooted in patient needs. Crinetics is focused on discovering, developing, and commercializing novel therapies, with a core expertise in targeting G-protein coupled receptors (GPCRs) with small molecules that have specifically tailored pharmacology and properties.
Crinetics’ first commercial product, PALSONIFY™ (paltusotine), is the first once-daily, oral treatment approved by the U.S. FDA and EMA for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. Paltusotine is also in clinical development for carcinoid syndrome associated with neuroendocrine tumors. Crinetics’ deep pipeline of 10+ disclosed programs includes late-stage investigational candidate atumelnant, which is currently in development for congenital adrenal hyperplasia and ACTH-dependent Cushing’s syndrome, and CRN09682, a nonpeptide drug conjugate candidate that is being developed to treat somatostatin receptor 2 (SST2) expressing neuroendocrine tumors and other SST2 expressing solid tumors. Additional discovery programs are focused on a variety of endocrine targets such as thyroid stimulating hormone (TSH), parathyroid hormone (PTH), somatostatin receptor 3 (SST3), growth hormone (GH), glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP), as well as GPCR-targeted oncology indications.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts contained in this press release are forward-looking statements, including statements regarding the plans and timelines for the clinical development of atumelnant for congenital adrenal hyperplasia and ACTH-dependent Cushing’s syndrome and PALSONIFY for carcinoid syndrome, including the therapeutic potential and clinical benefits or safety profile thereof; and the therapeutic potential for our development candidates. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplates,” “believes,” “estimates,” “predicts,” “potential,” “upcoming” or “continue” or the negative of these terms or other similar expressions. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, including, without limitation, initial or topline data that we report may change following completion or a more comprehensive review of the data related to the clinical studies and such data may not accurately reflect the complete results of a clinical study, and the FDA and other regulatory authorities may not agree with our interpretation of such results; geopolitical events may disrupt Crinetics’ business and that of the third parties on which it depends, including delaying or otherwise disrupting its clinical studies and preclinical studies, manufacturing and supply chain, or impairing employee productivity; the success of Crinetics’ clinical studies and nonclinical studies; regulatory developments in the United States and foreign countries; clinical studies and preclinical studies may not proceed at the time or in the manner expected, or at all; the timing and outcome of research, development and regulatory review is uncertain, and Crinetics’ drug candidates may not advance in development or be approved for marketing; and the other risks and uncertainties described in the Company’s periodic filings with the Securities and Exchange Commission (SEC). The events and circumstances reflected in the company’s forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Additional information on risks facing Crinetics can be found under the heading “Risk Factors” in Crinetics’ periodic filings with the SEC, including its annual report on Form 10-K for the year ended December 31, 2025 and quarterly report on Form 10-Q for the quarter ended March 31, 2026. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Except as required by applicable law, Crinetics does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.
Contact:
Media:
Natalie Badillo
Head of Corporate Communications
nbadillo@crinetics.com
(858) 345-6075
Investors:
Gayathri Diwakar
Head of Investor Relations
gdiwakar@crinetics.com
(858) 345-6340