Paltusotine (Palsonify) Tablets
November 15, 2025 4 minutes read
By William Elliott, MD, FACP, and James Chan, PharmD, PhD
The U.S. Food and Drug Administration has approved paltusotine, the second oral (after octreotide), but first once-daily formulation for the treatment of acromegaly in adults. Paltusotine is a nonpeptide selective somatostatin receptor 2 (SSTR2) ligand.1 It is distributed by Crinetics Pharmaceutical, Inc. as Palsonify.
Indications
Paltusotine is indicated for the treatment of adults with acromegaly who had inadequate response to surgery and/or for whom surgery is not an option.1
Dosage
The recommended dose is 40 mg once daily with water on an empty stomach at least six hours after a meal (e.g., after overnight fasting) and at least one hour before the next meal.1 The dose may be reduced to 20 mg once daily based on tolerability. After two to four weeks, based on insulin-like growth factor-1 (IGF-1) levels, it may be titrated to 60 mg once daily. Patients on moderate or strong cytochrome P450 3A4 inducers may require an increase in dosage (two-fold for moderate inducers to three-fold for strong inducers, up to 120 mg), whichever is less. Patients on a proton pump inhibitor also may require an increased dose. Proton pump inhibitors should not be started in patients already on paltusotine. Paltusotine is available as 20-mg and 40-mg tablets.
Potential Advantages
As a once-a-day oral formulation, paltusotine provides a more convenient way to treat adults with acromegaly, avoiding the adverse reactions associated with currently available injectable somatostatin analogs or receptor antagonists. Injection site adverse reactions are problematic with these agents (e.g., nodules, bruising, inflammation, scar tissue). In a survey of 195 patients, 70% self-reported injection site pain lasting up to a week with somatostatin analog injections (exclusively octreotide and lanreotide).2 Paltusotine is dosed once daily while oral octreotide delayed-released capsules are dosed twice daily.
Potential Disadvantages
Paltusotine inhibits gallbladder contractility and decreases bile secretion.Cholelithiasis was reported in study participants. Hyperglycemia, hypoglycemia, cardiac conduction abnormalities (e.g., PR interval prolongation, bradycardia), thyroid function abnormalities (e.g., hypothyroidism), steatorrhea, malabsorption of dietary fats, and vitamin B12 deficiency have been reported with paltusotine. The most common adverse reactions (vs. placebo) reported in the two clinical trials were diarrhea (23% to 33% vs. 11% to 14%, respectively), abdominal pain (13% to 19% vs. 4% to 5%, respectively), and nausea (9% to 13% vs. 2% to 4%, respectively).1
Comments
Paltusotine selectively binds to SSTR2, suppressing secretion of growth hormone and IGF-1.1 The safety and efficacy of paltusotine were evaluated in two randomized, double-blind, placebo-controlled, Phase III studies (PATHFNDR-2, PATHFNDER-1).1,3 In PATHFNDR-2, subjects (n = 111) had biochemically uncontrolled acromegaly. They were treatment-naive, had no treatment within the previous four months, or previously were treated on a somatostatin receptor analog and were washed out of treatment during screening. The study population had a mean age of 47 years, 53% were female, 52% were white, and 31% were Asian. The mean duration since diagnosis of acromegaly was 87 months, and 95% of participants had received pituitary surgery. Seventy-eight percent of participants had macroadenomas (> 10 mm). Participants were randomized to paltusotine (n = 54) or placebo (n = 57) for 24 weeks. The primary endpoint was the proportion of participants achieving biochemical control (IGF-1 level ≤ 1.0 × the upper limit of normal) compared to placebo-treated participants. At week 24, 56% of paltusotine recipients achieved the primary endpoint, compared to 5% for the placebo-treated participants. Paltusotine-treated participants had numerically lower patient-reported severity symptoms scores.1 These included headaches, joint pain, sweating, fatigue, weakness, and/or numbness/tingling.
In PATHFNDER-1, participants were previously biochemically controlled on injectable depot octreotide or lanreotide somatostatin analog formulations.1 The participants had a mean age of 55 years, 55% were female, 72% were white, 86% had received pituitary surgery, 57% had macroadenomas, and the mean duration since diagnosis was 155 months. They were randomized to paltusotine (n = 30) or placebo (n = 28) for 36 weeks. The proportion who maintained response (IGF-1 ≤ 1.0 × the upper limit of normal) were 83% for paltusotine vs. 4% for the placebo group. Similarly to the first study, participants had numerically lower severity of symptom scores. There are no trials comparing oral octreotide delayed-release capsules and paltusotine tablets. Comparing respective, Phase III, 36-week switch studies (injectable to oral or placebo), maintenance of biochemical control (IGF-1 ≤ 1.0 × the upper limit of normal) was 83.3% for paltusotine (vs. 3.6% for placebo) compared to 58% (vs. 19%) for oral octreotide.3,4 Twenty-five percent of octreotide-treated participants discontinued the drug/received rescue medication, compared to 6.7% of paltusotine-treated participants.
Clinical Implications
Acromegaly is caused by excessive production of growth hormone by the anterior pituitary gland, generally the result of a benign pituitary adenoma. The estimated prevalence is 5.9 cases per 100,000 individuals.5 Peptide injectable first-generation somatostatin receptor ligands (octreotide, lanreotide) are the standard of care for the non-surgical or non-radiation-based treatment of acromegaly. Pasireotide, a long-acting SSTR ligand, is considered second-line. Pegvisomant, a growth hormone receptor antagonist, also is an option. Paltusotine offers an orally effective, well-tolerated, once-daily, nonpeptide agent avoiding injection site-adverse reactions. Paltusotine, as Palsonify, is expected to cost $290,000 for one year of therapy.
William T. Elliott, MD, FACP, is Assistant Clinical Professor of Medicine, University of California, San Francisco.
James Chan, PharmD, PhD, is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
References
- Crinetics Pharmaceuticals, Inc. Palsonify prescribing information. Revised September 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219070s000lbl.pdf
- Strasburger CJ, Karavitaki N, Störmann S, et al. Patient-reported outcomes of parenteral somatostatin analogue injections in 195 patients with acromegaly. Eur J Endocrinol. 2016:174(3):355-362.
- 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. 2024;110(1):228-237.
- Amryt Pharmaceuticals Designated Activity Company. Mycapssa prescribing information. Revised July 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/208232s006lbl.pdf
- Reverdiau C, Deniaml D. Advances in the oral administration of somatostatin receptor ligands in acromegaly: A systematic review focusing on biochemical response. Pharmaceutics. 2024;16(11):1357.
The U.S. Food and Drug Administration has approved paltusotine, the second oral (after octreotide), but first once-daily formulation for the treatment of acromegaly in adults.
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