PATHFNDR-1: Switching from SRL injections
Rapid and reliable biochemical control1,5
Seamlessly maintained IGF-1 control in patients who switched from SRL injections1,2*
Maintained IGF-1 control of ≤1.0 × ULN at week 36 in 83% of patients taking PALSONIFY vs only 4% of patients taking placebo (primary endpoint, P<0.0001).1,2
*Octreotide or lanreotide.1
IGF-1=insulin-like growth factor 1; SRL=somatostatin receptor ligand; ULN=upper limit of normal.
MEAN IGF-1 BY VISIT2,5*
Exploratory endpoint†
Only 1 patient
taking PALSONIFY had an IGF-1 >1.1 × ULN at EOT2
Consistent symptom control
PALSONIFY reduced symptom severity vs placebo.3‡
Long-term IGF-1 control
96% of patients who maintained normal IGF-1 at the end of the randomized control period maintained biochemical control at month 22 in the extension study.1,6§
- *Last observation carried forward for patients who received rescue medication or discontinued from the study.5
- †Should not be interpreted as establishing clinical significance.
- ‡The change from baseline to week 36 in total ASD score (secondary endpoint) showed a statistically significant improvement of -0.6 for patients who took PALSONIFY compared to a worsening of 4.6 for patients on placebo (P=0.0216).3
- §Among patients who achieved IGF-1 normalization at week 36 of the randomized control period and completed the week 60 visit of the extension study, 22/23 (96%) maintained IGF-1 normalization at week 60 of the extension study.6
ASD=Acromegaly Symptom Diary; EOT=end of treatment (week 36 or last assessment before rescue).2,5
PATHFNDR-2 CLINICAL TRIAL
Learn how PALSONIFY worked for uncontrolled/
Patricia,
living with acromegalyA new tool was developed to monitor acromegaly symptoms in clinical trials11
The Acromegaly Symptom Diary (ASD) is a novel patient-reported outcome (PRO) tool. Built in accordance with FDA guidance, the ASD offers quantifiable insight into changes in acromegaly symptoms. It was designed to assess symptom severity and capture the day-to-day symptom burden that traditional biochemical markers may overlook.
The ASD in PATHFNDR studies
The ASD was used in PALSONIFY clinical trials to evaluate symptom control over time. It was completed daily during screening and during study treatment. Patients rated each symptom on a scale from 0 (no symptom) to 10 (worst symptom). The total ASD score is the weekly average of daily scores (the sum of a scored item over 1 week divided by the number of days on which the item was completed).The ASD tool measured symptom severity in 7 categories:
- Headache
- Joint pain
- Sweating
- Fatigue
- Weakness in legs
- Swelling
- Numbness or tingling
Study design
PATHFNDR-1 was a 36-week study that enrolled 58 patients whose acromegaly was biochemically controlled with SRL injections (octreotide or lanreotide). Patients were biochemically controlled (IGF-1 ≤1.0 × ULN) during screening and at randomization. Patients were randomized to receive either PALSONIFY (n=30) or placebo (n=28), and the primary endpoint was proportion of patients with biochemical control (maintenance) at week 36. The primary endpoint and all secondary endpoints were met.1,2*
- *Secondary endpoints included change from baseline in IGF-1 (measured as × ULN) at end of randomized treatment or the last assessment before rescue medication; change from baseline in total Acromegaly Symptom Diary (ASD) score at end of randomized treatment; and proportion of patients with mean 5-sample GH <1.0 ng/mL at week 34 among those with mean 5-sample GH <1.0 ng/mL during screening.2
- IGF-1=insulin-like growth factor 1; SRL=somatostatin receptor ligand; ULN=upper limit of normal.
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.
Please see Full Prescribing Information including Patient Information.
References: 1. PALSONIFY. Prescribing information 09/2025. Crinetics Pharmaceuticals, Inc; 2025. 2. Gadelha MR, Casagrande A, Strasburger CJ, et al. Acromegaly disease control maintained after switching from injected somatostatin receptor ligands to oral paltusotine. J Clin Endocrinol Metab. 2025;110(1):228-237. doi:10.1210/clinem/dgae385 3. Data on file. CRN00808-08 NDA 2.5 clinical overview. Crinetics Pharmaceuticals, Inc; 2025. 4. Gadelha MR, Wildemberg LE, Kasuki L. The future of somatostatin receptor ligands in acromegaly. J Clin Endocrinol Metab. 2022;107(2):297-308. doi:10.1210/clinem/dgab726 5. Clemmons D, Quock TP, Casagrande A, Wang Y, Krasner A. Paltusotine results in improved symptom stability in biochemically controlled acromegaly. Poster presented at: Endocrine Society Annual Meeting; July 12-15, 2025; San Francisco, CA. 6. Data on file. PATHFNDR studies week 60 open-label extension data and PATHFNDR-2 baseline IGF-1 levels. Crinetics Pharmaceuticals, Inc; 2025. 7. Data on file. Clinical study report CRN00808-08. Crinetics Pharmaceuticals, Inc; 2025. 8. Data on file. Clinical study report CRN00808-09. Crinetics Pharmaceuticals, Inc; 2025. 9. Data on file. CRN00808-08 NDA 2.7.4 summary of clinical safety. Crinetics Pharmaceuticals, Inc; 2025. 10. Data on file. CRN00808-08 NDA 2.7.3 summary of clinical efficacy. Crinetics Pharmaceuticals, Inc; 2025. 11. Martin S, Bender RH, Krasner A, Marmon T, Monahan M, Nelson L. Development and evaluation of the Acromegaly Symptom Diary. J Patient Rep Outcomes. 2023;7:15. doi:10.1186/s41687-023-00541-7