Paltusotine, approved in the United States as PALSONIFYTM, is a first-line treatment for adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. Paltusotine is an oral, once-daily, selectively-targeted somatostatin receptor type 2 (SST2) nonpeptide agonist. In addition to being approved in the United States, paltusotine is currently under review for use in the European Union and is also in development in Japan by Crinetics’ partner Sanwa Kagaku Kenkyuso. Paltusotine is also in clinical development for carcinoid syndrome associated with neuroendocrine tumors (NETs) as part of a global Phase 3 pivotal trial. Paltusotine has more than a 4,000-fold selectivity for SST2 compared with the other SST receptor subtypes, which may reduce the risk of off-target effects.
PALTUSOTINE
(ORAL SST2 AGONIST)
Therapeutic areas
Acromegaly
Somatostatin receptor ligands (SRLs) historically have been the primary pharmacotherapy for acromegaly patients who are candidates for chronic pharmacological intervention. The current standard of care in acromegaly involves monthly intramuscular or deep subcutaneous depot injections of peptide SRLs. Often, these peptide drugs fail to fully control the disease in many acromegaly patients.
There is a significant unmet need in the acromegaly market. For example, 77 percent of patients reported injection site reactions after SRL treatment and 52 percent had acromegaly symptoms worsen at the end of an SRL injection cycle. Patients and healthcare professionals need therapies with a rapid onset of action, sustained effect, favorable adverse event profile, and ease of use.
PALSONIFY™ (paltusotine), a selectively-targeted somatostatin receptor type 2 nonpeptide (SST2) agonist, is now the first once-daily, oral treatment approved for adults with acromegaly.
The approval is based on data from the PATHFNDR-1and PATHFNDR-2 Phase 3 pivotal trials, which evaluated PALSONIFY’s safety and efficacy in previously treated and medically untreated adults with acromegaly. Across both trials, PALSONIFY consistently demonstrated rapid onset, reliable biochemical control, and sustained efficacy. In addition, paltusotine was granted Orphan Drug Designation by the European Medicines Agency (EMA) and our Marketing Authorization Application (MAA) with the agency has been validated. For more details about the safety and efficacy of PALSONIFY, please see Full Prescribing Information here.
More on our research in acromegaly
Carcinoid syndrome
Carcinoid syndrome is a group of symptoms that may present in some patients with a specific type of cancer called neuroendocrine tumors (NETs). NETs are a rare, heterogenous type of cancer that originate from neuroendocrine cells, most often in the gastrointestinal tract, lungs, and pancreas.
Functional NETs can cause carcinoid syndrome, and it can develop if the original NET spreads from the small bowel (or other locations) to the liver. In these cases, the hormones the NET secretes cannot be filtered out by the liver as they normally would and so reach the circulatory system, causing the symptoms of carcinoid syndrome.
Most NETs express SST2 receptors and injected depots of SRLs have become the first-line standard of care for many NETs patients. Paltusotine is a nonpeptide, highly-selective SST2 agonist candidate that is taken as a once-daily oral tablet. Following a successful Phase 2 study, we have recently initiated a global Phase 3 clinical study for paltusotine in carcinoid syndrome.
More on our research in carcinoid syndrome
Our research
Acromegaly
Disease Control in Patients With Acromegaly Switching From Injected Somatostatin Receptor Ligands to Once-Daily Oral Paltusotine: Interim Results of the PATHFNDR-1 Open-Label Extension
Beverly M. K. Biller, MD et. Al.
Once-Daily Oral Paltusotine in the Treatment of Patients With Biochemically Uncontrolled Acromegaly: Interim Results of the PATHFNDR-2 Open-Label Extension
Monica R. Gadelha, MD, PhD et. Al.
Paltusotine Results in Improved Symptom Stability in Biochemically Controlled Acromegaly
David Clemmons, MD et. Al.
Effects of Paltusotine Treatment on Patient-Reported Symptoms of Acromegaly in Phase 3 Randomized Placebo-Controlled Studies (PATHFNDR-2 and PATHFNDR-1)
Avery A. Rizio, PhD et. al.
Efficacy and Safety of Once-Daily Oral Paltusotine in Medically Untreated Patients with Acromegaly: Results from the Phase 3, Randomized, Placebo-Controlled PATHFNDR-2 Study (2024)
Beverly M.K. Biller, MD, Alessandra Casagrande, MD, PhD, Atanaska Elenkova, MD, et al.
Paltusotine Maintains IGF-I, GH, and Symptom Control in Patients With Acromegaly Switched From Injected Octreotide or Lanreotide Monotherapy: Topline Results From PATHFNDR-1, a Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study (2023)
Monica R. Gadelha, MD, PhD, Alessandra Casagrande, MD, PhD, Christian J. Strasburger, MD; et al.
Acromegaly
Oral Once-Daily, Paltusotine (Non-Peptide Selective Somatostatin Receptor Subtype 2 Agonist) Therapy in Patients With Acromegaly is Associated With Long-Term Biochemical and Symptom Control and is Preferred Over Injectable Somatostatin-Receptor Ligands (2023)
Monica R. Gadelha, MD, PhD, Harpal Randeva, MBChB, FRCP, FAcad TM, PhD2, Murray B. Gordon, MD, et al.
Long-Term Safety and Efficacy of Once-Daily Oral Paltusotine in the Treatment of Patients With Acromegaly: Update From ACROBAT Advance (2024)
Monica R. Gadelha, MD, PhD, Harpal Randeva, MBChB, FRCP, FAcad TM, PhD, Murray B. Gordon, MD, et al.
ACROBAT Edge: Safety and Efficacy of Switching Injected SRLs to Oral Paltusotine in Patients with Acromegaly (2022)
Monica R. Gadelha, MD, PhD, Murray B. Gordon, MD, Mirjana Doknic, MD, PhD, et al.
ACROBAT Advance: Safety and Efficacy of Switching Injected SRLs to Oral Paltusotine in Patients with Acromegaly (2022)
Harpal Randeva, MBChB, FRCP, FAcad TM, PhD, Monica R. Gadelha, MD, PhD, Murray B. Gordon, MD, et al.
ACROBAT Advance: Long-term Safety and Efficacy Results of Paltusotine for the Treatment of Acromegaly (2021)
Harpal Randeva, PhD, Monica R. Gadelha, MD, PhD, Murray B. Gordon, MD, et al.
ACROBAT Edge Phase 2 Study: Safety and Efficacy of Switching Injected Long-Acting Somatostatin Receptor Ligands (SRLs) to Once-Daily Oral Paltusotine (2021)
Monica R. Gadelha, MD, PhD, Murray B. Gordon, MD, Mirjana Doknic, MD, PhD, et al.
Paltusotine Shows Long-term Safety and IGF-1 Maintenance in the ACROBAT Advance Study (2022)
Monica R. Gadelha, MD, PhD, Murray B. Gordon, MD, Mirjana Doknic, MD, PhD, et al.
Carcinoid Syndrome
A Phase 2, Randomized, Parallel Group Study to Evaluate the Safety, Pharmacokinetics, and Dose Response of Paltusotine Treatment in Subjects with Carcinoid Syndrome (2023)
Aman Chauhan, MD, Shagufta Shaheen, MD, Keith Usiskin, MD, et al.
Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Oral Paltusotine, a Non-Peptide, Selective Somatostatin Receptor Subtype 2 Agonist (2023)
Rosa Luo, MS, Alessandra Casagrande, MD, PhD, Sonic Oun, BA, et al.
Discovery of Paltusotine (CRN00808), a Potent, Selective, and Orally Bioavailable Non-peptide SST2 Agonist (2022)
Jian Zhao, PhD, Shimiao Wang, Stacy Markison, et al.
Paltusotine, a Novel Oral Once Daily Nonpeptide SST2 Receptor Agonist, Suppresses GH and IGF1 in Healthy Volunteers (2022)
Ajay Madan, PhD, Stacy Markison, Stephen F. Betz, PhD, et al.
Pharmacokinetics and Safety of an Improved Formulation of Paltusotine, a Selective, Nonpeptide Somatostatin Receptor 2 (SST2) Agonist for the Treatment of Acromegaly (2021)
Rosa Luo, Gerald Burk, Cosina Mui, et al.
Absolute Oral Bioavailability and Absorption, Metabolism, Excretion of [14C]-Labeled Paltusotine (CRN00808), an Orally Bioavailable, Nonpeptide, Selective, Somatostatin Receptor 2 (SST2) Biased Agonist for the Treatment of Acromegaly (2020)
Ajay Madan, PhD, Rosa Luo, Christine Ferrara-Cook, MD, MhD, et al.
Final Results from the First in Man Phase 1 Clinical Trial of CRN00808, an Orally Bioavailable SST2-Selective, Nonpeptide Somatostatin Biased Agonist for the Treatment of Acromegaly: Safety, Pharmacokinetics, Pharmacodynamics, and Midazolam Drug Interaction in Healthy Volunteers (2019)
Ajay Madan, PhD, Yun Fei Zhu, PhD, Stacy Markison, et al.
Paltusotine is an investigational drug candidate currently in clinical studies for carcinoid syndrome associated with neuroendocrine tumors (CAREFNDR). The safety and efficacy of paltusotine have not been established in this patient population. In clinical studies, paltusotine has been well-tolerated and the adverse drug reactions have been generally mild to moderate.
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