Palsonify (paltusotine) / Suzuken, Vertex - LARVOL DELTA

Phase 2 Study of Paltusotine in Patients With Neuroendocrine Tumors and Carcinoid Syndrome: Final Analysis of Investigator-Assessed Disease Progression (ESMO 2026) - No abstract available

Clinical • P2 data • Neuroendocrine Tumor • Oncology • Solid Tumor

Once-daily oral paltusotine in the treatment of patients with carcinoid syndrome: Biomarker analysis results from a phase 2, randomized, parallel-group study. (ASCO-GI 2026) - P2, P3 | "Paltusotine significantly reduced serotonin and 5-HIAA levels, with effects maintained at 48 weeks. Biomarker reductions paralleled reductions in BM and flushing frequency. These findings support further investigation in the ongoing phase 3 study (CAREFNDR, NCT07087054)."

Biomarker • Clinical • P2 data • Gastrointestinal Cancer • Oncology • SSTR • SSTR2

Investigator-assessed disease progression in a phase 2 study of paltusotine in patients with neuroendocrine tumors and carcinoid syndrome (ENETS 2026) - "In this preliminary analysis of a phase 2 study, the observed iaPFS rate (74%) after 1 year of treatment with paltuso - tine is encouraging and warrants further investigation in the ongo - ing CAREFNDR phase 3 study."

Clinical • P2 data • Carcinoid Syndrome • Neuroendocrine Tumor • Oncology • Solid Tumor

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 | Completed | Sponsor: Crinetics Pharmaceuticals, Inc | Not yet recruiting ➔ Completed | Initiation date: Nov 2025

Trial completion • Trial initiation date • Acromegaly • Carcinoid Syndrome • Endocrine Disorders

A Study to Evaluate the Long-Term Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (ACROBAT Advance) (clinicaltrials.gov) - P2 | N=43 | Terminated | Sponsor: Crinetics Pharmaceuticals Inc. | Trial completion date: Mar 2028 ➔ Jun 2026 | Active, not recruiting ➔ Terminated | Trial primary completion date: Mar 2028 ➔ Jun 2026; The study was stopped early for business reasons (not due to changes in the benefits or risks of paltusotine).

Trial completion date • Trial primary completion date • Trial termination • Acromegaly • Endocrine Disorders • IGF1

Phase 1 Study of Paltusotine, a Novel Oral Once‑Daily, Nonpeptide Selective Somatostatin Receptor 2 Agonist, in Healthy Japanese Adults. (PubMed, Clin Pharmacol Drug Dev) - "In the single-dose study, plasma paltusotine exposures increased in a dose-dependent manner for the dose range of 20 to 80 mg (based on Cmax and AUC0-∞), and the elimination half-life (t1/2) was 24-28 h. In the repeated-dose study, similar reductions from baseline in serum insulin-like growth factor-1 (IGF-I) were observed for 1-h pre-prandial (-60.1 ± 26.0 ng/mL) and 3-h post-prandial administration (-61.6 ± 17.7 ng/mL) on Day 7. Overall, this study establishes the pharmacokinetics, pharmacodynamics, and safety in healthy Japanese adults to support the development of paltusotine as a treatment for acromegaly and pituitary gigantism."

Journal • P1 data • Acromegaly • Endocrine Disorders • IGF1 • SSTR • SSTR2

Reduced breakthrough symptom exacerbations in patients with biochemically controlled acromegaly switched from injected depot somatostatin receptor ligands to once-daily oral paltusotine in the PATHFNDR-1 clinical trial. (PubMed, Pituitary) - "In patients with acromegaly biochemically controlled with injected SRLs, switching to once-daily oral paltusotine was associated with stable biochemical control, stable symptom severity, and a significantly 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."

Journal • Acromegaly • Endocrine Disorders • IGF1 • SSTR

A Study to Evaluate the Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (PATHFNDR-2) (clinicaltrials.gov) - P3 | N=111 | Terminated | Sponsor: Crinetics Pharmaceuticals Inc. | Trial completion date: Jan 2028 ➔ Jun 2026 | Active, not recruiting ➔ Terminated; The study was stopped early for business reasons (not due to changes in the benefits or risks of paltusotine).

Trial completion date • Trial termination • Acromegaly • Endocrine Disorders • IGF1

PATHFNDR 1: A Study to Evaluate the Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (clinicaltrials.gov) - P3 | N=58 | Terminated | Sponsor: Crinetics Pharmaceuticals Inc. | Trial completion date: Jun 2027 ➔ May 2026 | Active, not recruiting ➔ Terminated; The study was stopped early for business reasons (not due to changes in the benefits or risks of paltusotine).

Trial completion date • Trial termination • Acromegaly • Endocrine Disorders • IGF1

Palsonify (paltusotine); atumelnant / Vertex Pharmaceuticals; Crinetics Pharmaceuticals Vertex Pharmaceuticals…agreed to acquire Crinetics Pharmaceuticals for approximately $10 billion in cash (MSN News) - "The acquisition adds Palsonify, the first and only once-daily oral therapy for acromegaly, and late-stage candidate atumelnant for congenital adrenal hyperplasia (CAH)...The transaction is expected to close in the third quarter of 2026, subject to regulatory and shareholder approvals."

M&A • Acromegaly • Congenital Adrenal Hyperplasia

Safety and Efficacy of Once-Daily Oral Paltusotine in Acromegaly: ACROBAT Advance Open-Label Extension Up to 4 Years. (PubMed, J Clin Endocrinol Metab) - "Once-daily oral paltusotine treatment was well tolerated and resulted in long-term disease control, including biochemical, symptom, and pituitary tumor stability, for up to 4 years."

Journal • Acromegaly • Endocrine Disorders • Oncology • Pituitary Gland Carcinoma • IGF1 • SSTR

Safety and Efficacy of Oral Paltusotine in Patients with Acromegaly with or without Prior Somatostatin Receptor Ligand Maintenance: A GRADE-Assessed Systematic Review and Meta-Analysis of Randomized Controlled Trials (ENDO 2026) - "With a favorable, consistent safety profile compared with placebo, oral paltusotine demonstrates significant efficacy in improving biochemical control and symptom burden in patients with acromegaly. These findings support paltusotine as an effective oral therapeutic option for patients with acromegaly, including those with or without prior maintenance on somatostatin receptor ligands, although further large-scale trials are needed to confirm its long-term safety and durability of response."

Retrospective data • Review • Acromegaly • Diabetes • Dyslipidemia • Endocrine Disorders • Hypertriglyceridemia • Infectious Disease • Musculoskeletal Pain • Pituitary Gland Carcinoma • Respiratory Diseases • IGF1 • SSTR • SSTR2

Comparative Efficacy and Safety of Oral vs Injectable Medical Therapies for Acromegaly: A Systematic Review and Network Meta-Analysis (ENDO 2026) - "SUCRA rankings favored Pasireotide, paltusotine, pegvisomant for efficacy, while oral octreotide ranked highest for safety and patient preference, reflecting reduced injection-site reactions and improved treatment acceptability. Conclusion This network meta-analysis demonstrates that while pasireotide and pegvisomant provide the highest efficacy, paltusotine emerges as the most effective oral therapy, offering a favorable balance of biochemical control, safety, and patient acceptability."

Retrospective data • Review • Acromegaly • Endocrine Disorders • IGF1

Long-Term Safety and Efficacy of Once-Daily Oral Paltusotine in Combination with Cabergoline for the Treatment of Patients with Acromegaly (ENDO 2026) - P2 | "At enrollment in Edge, all patients were candidates for combination drug therapy: patients were either suboptimally controlled on an injected SRL (octreotide or lanreotide) alone or in combination with cabergoline, or they required combination therapy or pasireotide to achieve normal IGF-I levels...Adjunctive treatment (eg, cabergoline, pegvisomant) was allowed as of Week 12 in patients who did not attain normal IGF-I levels on the maximum dose of paltusotine...One serious drug-related AE (cholelithiasis) was reported, and 1 patient discontinued the study due to an AE (headache; considered possibly related to study medication). In patients with acromegaly who were candidates for combination therapy based on treatment history, long-term results (up to 4 years) show that once-daily oral paltusotine in combination with cabergoline was well tolerated, with improved biochemical control and no new safety findings."

Clinical • Combination therapy • Acromegaly • Endocrine Disorders • Gastroenterology • Musculoskeletal Pain • IGF1 • SSTR

ORF28-06 - Efficacy and Safety of Once-Daily Oral Paltusotine in Patients with Acromegaly: Up to 2 Years in the PATHFNDR-1 and PATHFNDR-2 Open-Label Extension Studies (ENDO 2026) - No abstract available

Clinical • Acromegaly • Endocrine Disorders

SI01-08 - Advancing Acromegaly Management: Bridging Clinical Evidence and the Patient Journey with PALSONIFY™ (paltusotine) (ENDO 2026) - "Speakers will review key clinical challenges, treatment goals, and decision making considerations across treatment naïve and previously treated patients. The session will also highlight clinical trial evidence supporting the role of once daily oral PALSONIFY™ (paltusotine) in achieving biochemical and symptom control."

Clinical • Acromegaly • Endocrine Disorders

PATHFNDR 1: A Study to Evaluate the Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (clinicaltrials.gov) - P3 | N=58 | Active, not recruiting | Sponsor: Crinetics Pharmaceuticals Inc. | Completed ➔ Active, not recruiting

Enrollment closed • Acromegaly • Endocrine Disorders • IGF1 • SSTR

Crinetics Pharmaceuticals Announces the European Commission Approval of PALSONIFY (Paltusotine) for the Treatment of Acromegaly in Adults (GlobeNewswire) - "The EC approval is supported by positive results from the pivotal data from the PATHFNDR-1 and PATHFNDR-2 Phase 3 trials, which evaluated PALSONIFY’s safety and efficacy in previously treated and medically untreated adults with acromegaly....The approval by the EC is valid in all 27 member states of the EU and three European Economic Area (EEA) countries. Crinetics is currently planning initial commercialization efforts in Germany and Austria."

EMA approval • Acromegaly

Once-Daily Oral Paltusotine in the Treatment of Adults With Acromegaly: Initial Real-World Experience (AACE 2026) - "Patient 2 had elevated IGF-I (621 ng/mL) 4 months after repeat Discussion/Conclusion Based on data obtained from a limited number of pituitary centers during the first 4 months following US approval, paltusotine was prescribed to patients with varied histories of treatment for acromegaly, including as first-line medical therapy, in patients who failed treatment with cabergoline and/or an injected depot somatostatin receptor ligand, and as add-on therapy to pegvisomant. Preliminary data indicate that paltusotine was effective in normalizing IGF-I levels and ameliorating"

Clinical • Real-world • Real-world evidence • Acromegaly • Endocrine Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pituitary Gland Carcinoma • IGF1 • SSTR

Concomitant Use of Paltusotine and Levothyroxine in Patients With Acromegaly: A Post Hoc Analysis of Phase 3 Clinical Trial Data (AACE 2026) - "Currently there are no data showing specific drug-drug interactions between paltusotine and levothyroxine. Although periodic assessment of thyroid function and IGF-I levels is recommended in patients treated for acromegaly with SRLs, these findings"

Clinical • P3 data • Retrospective data • Acromegaly • Endocrine Disorders • IGF1 • SSTR

Lunch Product Theater: Advancing What’s Possible with PALSONIFY™ (paltusotine) in Acromegaly: A Case‑Based Discussion Sponsored by Crinetics Pharmaceuticals (AACE 2026) - "The session will also highlight clinical trial evidence supporting the role of once‑daily oral paltusotine (PALSONIFY™️) in achieving biochemical and symptom control. This program is sponsored by Crinetics Pharmaceuticals."

Clinical • Acromegaly • Endocrine Disorders

Satellite Symposia Dinner: Advancing Precision Diagnosis and Treatment Strategies in Acromegaly: A Q-Challenge Live Clinical Decision Experience (AACE 2026) - "Faculty will also discuss emerging therapies, including once-daily oral paltusotine, with insights from the PATHFNDR-1 and PATHFNDR-2 trials. Planned by: Global Learning Collaborative Provided by an Education Grant from: Crinetics Pharmaceuticals You can also register HERE."

Clinical • Acromegaly • Endocrine Disorders

Current Treatment Landscape of Acromegaly. (PubMed, J Clin Endocrinol Metab) - "Pasireotide long-acting release, a somatostatin receptor multiligand, achieves more favorable biochemical control rates but is associated with an increased risk of hyperglycemia. Pegvisomant, a GH receptor antagonist, can be used as monotherapy or in combination with SRLs. The spectrum of medical therapy has expanded with the advent of oral octreotide capsules; the oral selective somatostatin receptor subtype 2 agonist, paltusotine; and monthly self-administered subcutaneous octreotide. This review outlines the updates to current acromegaly treatment options and their impact on patient outcomes."

Journal • Acromegaly • Diabetes • Endocrine Disorders • SSTR

Developments in Pharmacotherapy for Acromegaly: Current and Emerging Approaches. (PubMed, Drugs) - "Medical therapies in current use for acromegaly are somatostatin receptor ligands (SRLs) (octreotide long-acting release [LAR], octreotide acetate, lanreotide depot, octreotide subcutaneous (SC) depot, pasireotide LAR, oral octreotide, paltusotine), dopamine agonists (cabergoline) and growth hormone receptor antagonists (pegvisomant)...Several investigational drugs are in development towards addressing unmet needs of patients with acromegaly, including new formulations of SRLs (lanreotide prolonged-release formulation, Debio 4126, pasireotide SC depot), novel SRLs (somatoprim, HTL0030310), monoclonal antibodies against growth hormone, and new growth hormone receptor antagonists. Current and emerging therapies are offering renewed hope for disease control. More studies including comparator agents, identification of accurate biomarkers and models predictive of clinical effectiveness may further improve the care of patients with acromegaly."

Journal • Review • Acromegaly • Endocrine Disorders • SSTR

A Study to Evaluate the Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (PATHFNDR-2) (clinicaltrials.gov) - P3 | N=111 | Completed | Sponsor: Crinetics Pharmaceuticals Inc. | Active, not recruiting ➔ Completed | Completed ➔ Active, not recruiting

Enrollment closed • Trial completion • Acromegaly • Endocrine Disorders • IGF1