Palsonify (paltusotine) / Crinetics, Suzuken - LARVOL DELTA

Paltusotine Hydrochloride. (PubMed, Am J Health Syst Pharm) - No abstract available

Journal

PALSONIFY (Paltusotine) Launched in the U.S. with Encouraging Early Feedback from Patients and Physicians, and Positive Reimbursement Trends (Crinetics Press Release) - "Additionally, approximately 95% of filled prescriptions are from switch patients and 5% are from naïve patients, reflecting the demographics of the acromegaly population. Payer reimbursement has not been a barrier to treatment, with approximately 50% of filled prescriptions reimbursed."

Launch US • Acromegaly

A Phase 1, Single-Dose, Open-Label, Randomized, Three-Period, Two-Sequence, Crossover Study to Evaluate the Relative Bioavailability of Paltusotine Low Drug Load (LDL) Tablets 60 mg (2 × 30 mg LDL tablet) and High Drug Load (HDL) Tablet 60 mg (1 × 60 mg HDL tablet) in Healthy Volunteers. (ANZCTR) - P1 | N=20 | Not yet recruiting | Sponsor: Crinetics Pharmaceuticals, Inc

New P1 trial • Acromegaly • Carcinoid Syndrome • Endocrine Disorders

Paltusotine: The first selective nonpeptide agonist of somatostatin receptor 2 (SSTR2) for the treatment of acromegaly. (PubMed, Drug Discov Ther) - "With its rapid onset and durable biochemical control, this novel agent has the potential to reshape the current paradigm of acromegaly pharmacotherapy and offer patients a more convenient and effective treatment option. Nevertheless, its long-term safety and efficacy warrant further evaluation in real-world clinical settings."

Journal • Acromegaly • Endocrine Disorders • Pain • IGF1 • SSTR • SSTR2

Rapid and Sustained Response of Biochemically Uncontrolled Acromegaly to Once-Daily Oral Paltusotine Treatment. (PubMed, J Clin Endocrinol Metab) - "IGF-I normalized in significantly more patients with uncontrolled acromegaly treated with paltusotine versus placebo. Paltusotine was associated with rapid, sustained IGF-I reduction, significant symptom improvement, and stable or reduced pituitary tumor size and was well tolerated."

Clinical • Journal • Acromegaly • Endocrine Disorders • Oncology • Pain • Pituitary Gland Carcinoma • IGF1 • SSTR • SSTR2

Paltusotine versus octreotide: different effects on radioligand uptake in neuroendocrine tumours. (PubMed, Endocr Oncol) - "Treatment with paltusotine did not significantly reduce radioligand binding of 18F-SiTATE in vitro, indicating no influence on SSTR2 targeting. This might enable a continuation of somatostatin receptor analogue therapy with paltusotine during PRRT, potentially improving symptom control in GEP-NET patients with the carcinoid syndrome."

Journal • Carcinoid Syndrome • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR • SSTR2

Crinetics to Highlight Neuroendocrine Tumor Research Progress at the 2025 North American Neuroendocrine Tumor Society Annual Meeting (Crinetics Press Release) - "A preliminary analysis of Phase 2 data from the open-label trial of paltusotine in the treatment of patients with carcinoid syndrome due to NETs will be featured in a poster presentation, showing an overall investigator-assessed progression free survival rate of 74% following one year of treatment....Two additional poster presentations will feature study details from the randomized, Phase 3 trial of paltusotine in carcinoid syndrome due to NETs and the first-in-human study of NDC candidate CRN09682 in patients with somatostatin receptor 2-expressing tumors."

Clinical data • Carcinoid Syndrome • Neuroendocrine Tumor

Investigator-Assessed Disease Progression in a Phase 2 Study of Paltusotine in Patients with Neuroendocrine Tumors and Carcinoid Syndrome (NANETS 2025) - "Other reported targetable alterations in GEP-NENs include KRAS, ALK, BRCA1/2, ATM, NTRK, FGFR, and RET. CONCLUSIONS The observed PFS rate (74%) after 1 year of treatment with paltusotine, in this preliminary analysis of a phase 2 study, is encouraging data and warrants further investigation in the ongoing CAREFNDR Phase 3 study."

Clinical • P2 data • Neuroendocrine Tumor • Oncology • Solid Tumor • ALK • BRAF • BRCA1 • BRCA2 • FGFR • KRAS • NTRK • SSTR

CAREFNDR: Phase 3, Randomized, Placebo-Controlled Study of Paltusotine in Adults With Carcinoid Syndrome Due to Well-Differentiated Neuroendocrine Tumors (NANETS 2025) - P2 | "Global enrollment in CAREFNDR is ongoing. RESULTS N/A CONCLUSIONS N/A"

Clinical • P3 data • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR

Crinetics Announces FDA Approval of PALSONIFY (paltusotine) for the Treatment of Adults with Acromegaly (GlobeNewswire) - "The approval is based on data from the PATHFNDR-1 and PATHFNDR-2 Phase 3 pivotal trials...PALSONIFY is expected to be available in the U.S. in early October....A Marketing Authorization Application (MAA) for paltusotine in acromegaly is currently under review for use in the European Union, and the current timeline for the Committee for Medicinal Products and Human Use (CHMP) opinion is the first half of 2026."

CHMP • FDA approval • Launch US • 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 (ENDO 2025) - "PATHFNDR-1 was a randomized, double-blind, placebo-controlled trial that evaluated the efficacy and safety of switching to paltusotine in patients whose acromegaly was controlled (IGF-I ≤1.0× ULN) with injected depot somatostatin receptor ligands (SRLs; octreotide LAR or lanreotide depot). In conclusion, once-daily oral paltusotine maintained biochemical and symptom control and was well tolerated during long-term treatment in patients with acromegaly who switched from injected SRLs. Support: Crinetics Pharmaceuticals"

Clinical • Acromegaly • Carcinoid Syndrome • Endocrine Disorders • Fatigue • Infectious Disease • Musculoskeletal Diseases • Musculoskeletal Pain • Nephrology • Orthopedics • Pain • IGF1 • SSTR

Effects of Paltusotine Treatment on Patient-Reported Symptoms of Acromegaly in Phase 3 Randomized Placebo-Controlled Studies (PATHFNDR-2 and PATHFNDR-1) (ENDO 2025) - "ECDFs also showed that in PF-2, greater percentages of patients treated with paltusotine – regardless of prior treatment history – experienced improvement or stability of acromegaly symptoms, as compared to patients on placebo.Treatment with oral paltusotine promotes improvement and/or stability of acromegaly symptoms relative to placebo, as measured by the ASD. These findings demonstrate the benefit of paltusotine in addressing core symptoms of acromegaly that are most relevant to patients, in addition to its GH and IGF-1 lowering effects."

Clinical • P3 data • Acromegaly • Endocrine Disorders • Fatigue • Musculoskeletal Diseases • Musculoskeletal Pain • Oncology • Orthopedics • Pain • Rare Diseases • IGF1

Key Upcoming Milestones: (Yahoo Finance) - "Crinetics expects to initiate the CAREFNDR Phase 3 trial of paltusotine in carcinoid syndrome in the second half of 2025."

New P3 trial • Carcinoid Syndrome

Paltusotine Results in Improved Symptom Stability in Biochemically Controlled Acromegaly (ENDO 2025) - "We hypothesized that patients switched from injected long-acting octreotide or lanreotide (SRLs) to once-daily oral paltusotine would experience maintenance of biochemical and symptom severity control with reduced frequency of symptom exacerbations. A simple daily symptom-assessment tool provided important information pertaining to acromegaly disease control that was not apparent from IGF-I measurements. Support: Crinetics Pharmaceuticals"

Acromegaly • Endocrine Disorders • IGF1

CAREFNDR: Carcinoid Syndrome Efficacy Study Featuring an Oral Daily Paltusotine Regimen (clinicaltrials.gov) - P3 | N=141 | Recruiting | Sponsor: Crinetics Pharmaceuticals Inc.

New P3 trial • Carcinoid Syndrome • Carcinoid Tumor • Gastrointestinal Cancer • Liver Cancer • Neuroendocrine Tumor • Pancreatic Cancer • Small Intestinal Carcinoma • Solid Tumor

Once-daily Oral Paltusotine In The Treatment Of Patients With Biochemically Uncontrolled Acromegaly: Interim Results Of The PATHFNDR-2 Open-label Extension (ENDO 2025) - "In conclusion,IGF-I levels decreased rapidly in patients who had received placebo during theRC phase and patients with elevated IGF-I who were directly enrolled into theOLE, and the previously observed decrease was sustained in patients whocontinued on once-daily oral paltusotine. Paltusotine was well tolerated duringlong-term treatment."

Clinical • Late-breaking abstract • Acromegaly • Carcinoid Syndrome • Endocrine Disorders • IGF1

Oral, Once-Daily Paltusotine in the Treatment of Acromegaly (ESPE-ESE 2025) - "Sponsored by Crinetics Pharmaceuticals sponsored Mini-satellite session."

Acromegaly • Endocrine Disorders

Advancing GPCR Science Toward Future Treatments in Acromegaly, Congenital Adrenal Hyperplasia, and ACTH-dependent Cushing’s Syndrome. A Crinetics Pharmaceuticals sponsored Mini-satellite session. (ESPE-ESE 2025) - "Funded by Crinetics Pharmaceuticals has developed a distinctive science platform centered around nonpeptide small molecules targeting G protein-coupled receptors (GPCRs) to address endocrine diseases and related tumors. This platform leverages Crinetics' deep expertise in cell receptor biology to create orally administered therapeutics with improved specificity and pharmacokinetics compared to traditional peptide-based drugs.Crinetics’ pipeline will be reviewed, and results from clinical studies of paltusotine (an investigational oral SST2 agonist for acromegaly and carcinoid syndrome) and atumelnant (an investigational oral MC2R/ACTH antagonist for ACTH-dependent Cushing’s Syndrome and Congenital Adrenal Hyperplasia) will be presented."

Acromegaly • Carcinoid Syndrome • Congenital Adrenal Hyperplasia • Cushing’s Disease • Endocrine Disorders • Oncology

Long-Term Safety and Efficacy of Once-Daily Oral Paltusotine in the Treatment of Patients With Acromegaly: ACROBAT Advance Year 4 Analysis (ESPE-ESE 2025) - "In Edge, at enrollment all patients were candidates for combination drug therapy: either sub-optimally controlled on an injected SRL (octreotide or lanreotide) alone or in combination with cabergoline, or required combination therapy or pasireotide to achieve normal IGF-I levels...Adjunctive treatment with cabergoline or pegvisomant was allowed in patients who did not attain normal IGF-I levels on the maximum dose of paltusotine... Long-term results (up to ~4 years) show that once-daily oral paltusotine treatment was well tolerated, with stable biochemical and symptom control relative to that observed with injected SRLs."

Clinical • Acromegaly • Carcinoid Syndrome • Endocrine Disorders • Gastroenterology • IGF1

Crinetics Pharmaceuticals Announces European Medicines Agency (EMA) Validation of Marketing Authorization Application (MAA) and Orphan Drug Designation (ODD) for Paltusotine in Acromegaly (GlobeNewswire) - "Crinetics Pharmaceuticals...announced that the European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) for paltusotine, the first once-daily, oral, selectively-targeted somatostatin receptor type 2 nonpeptide agonist, for the proposed treatment and long-term maintenance therapy of acromegaly, a serious, rare and progressive endocrine disorder characterized by consistently elevated levels of growth hormone. The MAA will now be reviewed by the Committee for Medicinal Products for Human Use (CHMP). Additionally, the EMA on February 27, 2025 granted paltusotine Orphan Drug Designation (ODD) for the treatment of acromegaly....The MAA submission is supported by data from 18 clinical trials, including two Phase 3 trials that evaluated paltusotine for the treatment of acromegaly in medically untreated and treated patients."

EMA filing • Orphan drug • Acromegaly

CAREFNDR: A phase III, randomised, parallel group, placebocontrolled study to evaluate the efficacy and safety of paltusotine in adults with carcinoid syndrome due to well-differentiated neuroendocrine tumours (ENETS 2025) - No abstract available

Clinical • P3 data • Carcinoid Syndrome • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor

Oral paltusotine, a nonpeptide selective somatostatin receptor 2 agonist: Mass balance, absolute bioavailability and metabolism in healthy participants. (PubMed, Br J Clin Pharmacol) - "Oral dosing with paltusotine is associated with efficient absorption from the gastrointestinal tract. Most of the administered dose is excreted unchanged. Pharmacokinetic properties of paltusotine are supportive of once-daily dosing."

Journal • Acromegaly • Carcinoid Syndrome • Endocrine Disorders • Gastrointestinal Disorder • SSTR • SSTR2

Once-daily oral paltusotine in the treatment of patients with carcinoid syndrome: Safety and exploratory efficacy results from a phase II, randomised, parallel-group study (ENETS 2025) - "No new safety signals were identified. CONCLUSION In this phase 2 study, treatment with once-daily, oral paltusotine reduced the frequency and severity of CS symptoms and was well tolerated, justifying further clinical development."

Clinical • P2 data • Carcinoid Syndrome • CNS Disorders • SSTR

Once-daily oral paltusotine in the treatment of patients with carcinoid syndrome: Safety and exploratory efficacy results from a phase 2, randomised, parallel-group study (ENETS 2025) - No abstract available

Clinical • P2 data • Carcinoid Syndrome

Crinetics Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update (GlobeNewswire) - "Key Upcoming Milestones: FDA Prescription Drug User Fee Act (PDUFA) target action date of September 25, 2025 for paltusotine NDA for the treatment and maintenance therapy of acromegaly."

PDUFA • Acromegaly