Paltusotine is the first investigational once-daily, oral, selective somatostatin receptor type 2 (SST2) nonpeptide agonist that is in clinical development for acromegaly and carcinoid syndrome associated with neuroendocrine tumors (NETs). 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.
Investigational paltusotine is a nonpeptide, highly-selective SST2 agonist investigational candidate that is administered as a once-daily oral tablet.
Our clinical development program in acromegaly included two Phase 3 double-blind, placebo-controlled studies and was designed to support the potential of paltusotine as a maintenance therapy and in those patients not receiving pharmacotherapy. The New Drug Application (NDA) for paltusotine is currently under review by the U.S. Food and Drug Administration (FDA) for its use as a treatment for acromegaly. 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.
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. The safety and efficacy of paltusotine have not been established. In clinical studies, paltusotine has been well-tolerated and the adverse drug reactions have been generally mild to moderate.
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