PATHFNDR-2: Uncontrolled/
Rapid and reliable biochemical control1
IGF-1 control of ≤1.0 × ULN achieved1
in 56% of patients taking PALSONIFY by month 6 vs only
IGF-1=insulin-like growth factor 1; ULN=upper limit of normal.
MEAN IGF-1 CHANGE FROM BASELINE BY VISIT1,3
Exploratory endpoint*
93% of patients taking PALSONIFY had reductions in IGF-110
Only 1 patient taking PALSONIFY received rescue therapy vs 13 patients taking placebo1†
Consistent symptom control
Patients taking PALSONIFY significantly improved overall symptom control vs a worsening of symptoms with placebo.3‡
Long-term IGF-1 control
93% of patients who achieved IGF-1 normalization at the end of the randomized control period maintained biochemical control at month 19 in the extension study.1,6§
- *Should not be interpreted as establishing clinical significance.
- †Rescue therapy with standard-of-care treatment was initiated if a participant had evidence of uncontrolled acromegaly based on IGF-1 levels and symptoms.1
- ‡Symptoms for patients taking PALSONIFY improved based on an ASD score change (secondary endpoint) of -2.7 vs symptoms worsening based on a change in ASD score of 2.8 for patients taking placebo (P=0.0039).3
- §Among patients who achieved IGF-1 normalization at week 24 of the randomized control period and completed the week 60 visit of the extension study, 27/29 (93%) maintained IGF-1 normalization at week 60 of the extension study.6
ASD=Acromegaly Symptom Diary; BL=baseline.
PATHFNDR-1 CLINICAL TRIAL
Learn how PALSONIFY worked for patients switching from SRL injections
SRL=somatostatin receptor ligand.
David,
living with acromegalyINDICATION:
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
A 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-2 was a 24-week study that enrolled 111 adult patients with acromegaly who were not receiving medical treatment and were biochemically uncontrolled at randomization. Patients were either not previously medically treated or had no treatment within the previous 4 months prior to screening or were receiving, and washed out of, SRL injections (octreotide or lanreotide). Patients were randomized to receive either PALSONIFY (n=54) or placebo (n=57), and the primary endpoint was proportion of patients with achievement of biochemical control at week 24. The primary endpoint and all secondary endpoints were met.1,3*
- *Secondary endpoints included change from baseline in IGF-1 (measured as × ULN) at end of randomized treatment; proportion of patients who achieved IGF-1 <1.3 × ULN at end of randomization; 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 22 among those with mean 5-sample GH <1.0 ng/mL during screening.3,7
- GH=growth hormone; IGF-1=insulin-like growth factor 1; SRL=somatostatin receptor ligand; ULN=upper limit of normal.