Signifor (pasireotide) / Recordati - LARVOL DELTA

Clinical Implications of Molecular and Genetic Biomarkers in Cushing's Disease: A Literature Review. (PubMed, J Clin Med) - "The immunohistochemical evaluation of its granulation pattern, Ki-67 proliferation index, and E-cadherin expressions have been linked to a tumor's invasiveness and surgical outcomes, while somatostatin and dopamine receptor expressions may influence its response to Pasireotide and cabergoline therapy. This narrative review provides an update on the latest evidence regarding the roles of molecular biomarkers in corticotropinomas, emphasizing their role in prognosis, recurrence risk, and the response to different treatment options. A better understanding and integration of these biomarkers into clinical practice could lead to a better patient stratification, more efficient therapeutic strategies, and personalized treatment approaches for patients with CD."

Biomarker • Journal • Review • Cushing’s Disease • Endocrine Cancer • Endocrine Disorders • Gene Therapies • Neuroendocrine Tumor • Oncology • Rare Diseases • Solid Tumor • CDH1 • TP53 • USP8

Pasireotide Exerts Anti-Inflammatory Effects in the Endothelium. (PubMed, J Biochem Mol Toxicol) - "Endothelial cells were treated with PAS before LPS exposure to evaluate the corresponding effects on cell viability, inflammation, and barrier function. Since PAS suppressed LPS-triggered endothelial injury, it is suggested that this compound could be repurposed for endothelium-dependent disorder treatment."

Journal • Inflammation • SSTR

Cost-effectiveness analysis of second-line medical therapies in acromegaly: a real-life study. (PubMed, Front Endocrinol (Lausanne)) - "To assess the use of pasireotide and pegvisomant in a third-level center under routine clinical practice. Pasireotide affected carbohydrate metabolism (P = .001), but the effect was generally mild. Pasireotide was found to be a more cost-effective option in patients with first-line treatment failure."

HEOR • Journal • Acromegaly • Diabetes • Endocrine Disorders • Metabolic Disorders • Type 2 Diabetes Mellitus

PASIPHY: Pasireotide s.c. in Patients With Post-Bariatric Hypoglycaemia (clinicaltrials.gov) - P2 | N=72 | Recruiting | Sponsor: RECORDATI GROUP | Trial primary completion date: Apr 2025 ➔ Apr 2026

Trial primary completion date • Hypoglycemia • SSTR

Osilodrostat effectiveness in the treatment of Cushing's disease (CD) and ectopic Cushing’s syndrome (ECS)- a single-center real-life experience (ESPE-ESE 2025) - "Osilodrostat was first-line in 11, second-line in 10 (after metyrapone, ketoconazole, or pasireotide), and third/fourth-line in 2...At osilodrostat initiation: 17 required potassium supplementation (9 needed spironolactone), 19 had diabetes (9 on insulin), 21 had hypertension...Of 23 analyzable patients (13 CD, 10 ECS), mean diagnosis age was 57.8 years; 61% were women. Seven (30.4%) died. Mean morning serum cortisol at diagnosis: 42.7 μg/dL; ACTH: 180.3 pg/mL."

Clinical • Cardiovascular • Cushing’s Disease • Diabetes • Endocrine Disorders • Hypertension • Metabolic Disorders

Pasireotide Induces Long-term Cystic Degeneration of Somatotrophic Pituitary Neuroendocrine Tumors (PitNETs) (ESPE-ESE 2025) - "Background: Pasireotide LAR is a long-acting somatostatin analog with potential antitumor activity, as demonstrated by treatment induced increased MRI T2-signal intensity of somatotrophic PitNETs (1), but long- term follow-up data are lacking. Forty-four patients, 43 % female, median (IQR) age 52 (15 years) were included. Median treatment duration was 31.0 months. The median IR of the PitNETs increased between baseline and MRI at 7 years (1.09 vs."

Acromegaly • Endocrine Cancer • Endocrine Disorders • Neuroendocrine Tumor • Oncology • Solid Tumor • IGF1

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

Long-term safety of pasireotide in patients with acromegaly: Final results from a 10-year open-label Phase IV rollover study (B2412) (ESPE-ESE 2025) - P4 | "Here, we report data from the final analysis in patients with acromegaly who received pasireotide long-acting release (LAR) during the rollover. Pasireotide is a well-tolerated long-term treatment option for patients with acromegaly, with patients having received treatment for ≤17 years from parent study entry. Hyperglycaemia was infrequent, and AEs, including hyperglycaemia, were mostly manageable without treatment discontinuation during the rollover."

Clinical • P4 data • Acromegaly • Back Pain • Cardiovascular • Congestive Heart Failure • Cushing’s Disease • Diabetes • Endocrine Disorders • Growth Hormone Deficiency • Heart Failure • Hypertension • Infectious Disease • Metabolic Disorders • Musculoskeletal Pain • Novel Coronavirus Disease • Pain • Pulmonary Embolism • Respiratory Diseases • SSTR

Medical treatment in acromegaly: imunohistochemical features of responder patients (ESPE-ESE 2025) - "Materials and The retrospective analysis included 38 naive acromegaly patients (without preoperative medical treatment), with active disease following transsphenoidal (TS) surgery, treated with octreotide / lanreotide (n=38) or pasireotide (n=9) and/or pegvisomant (n=8) if uncontrolled under first generation SRLs (fgSRLs). Pituitary neuroendocrine tumor granularity represents a good predictor for the response to first and second generation SRLs in active acromegaly. Besides this, SSTR5 expression is predictive for the response to pasireotide. There are distinct IHC profiles that may help predict response to targeted medical therapy in acromegaly, and treatment should be initiated and individualized based on postoperative IHC features."

Clinical • Acromegaly • Endocrine Cancer • Endocrine Disorders • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR • SSTR2 • SSTR5

Dealing with Pituitary Invaders: A Corticotroph Macroadenoma Case (ESPE-ESE 2025) - "Medical management included ketoconazole, cabergoline, and the planned introduction of Pasireotide to address tumor control and residual hypercortisolism. Advanced therapies, like Pasireotide, offer promising outcomes in managing persistent disease. This case underscores the importance of individualized care in achieving optimal results for complex pituitary tumors."

Clinical • Cardiovascular • Cushing’s Disease • Diabetes • Endocrine Cancer • Endocrine Disorders • Hypertension • Metabolic Disorders • Oncology • Pituitary Gland Carcinoma • Type 2 Diabetes Mellitus

The clinical course and the systemic inflammation biomarkers (SIBs) differ between giant and not-giant aggressive prolactinomas. (ESPE-ESE 2025) - "Other therapeutic options included temozolomide (1/22), pasireotide (1/22), and lanreotide (3/22). The clinical course of the disease and SIBs differ between giant and not-giant aggressive prolactinomas. Further studies are needed to understand the nature of this condition. Keywords: Aggressive prolactinoma, prolactinoma, cabergoline, pasireotide"

Biomarker • Clinical • Inflammation • Oncology • Pain • Retinal Disorders

A Case of Aggressive AIP-Mutated Pituitary Acrogigantism Treated with Pasireotide. (ESPE-ESE 2025) - "Due to his hyperprolactinemia, cabergoline was started and rose to a dose of 0.5-1.0 mg/day. Pasireotide long-acting release treatment may be beneficial in AIP mutated patients with acrogigantism and positive immunohistochemical staining of tumour cells for SSTR5."

Clinical • Acromegaly • Anorexia • Back Pain • Cardiovascular • Endocrine Cancer • Endocrine Disorders • Musculoskeletal Pain • Neuroendocrine Tumor • Oncology • Ophthalmology • Pain • Pituitary Gland Carcinoma • Rare Diseases • Solid Tumor • IGF1 • SSTR2 • SSTR5

Combined therapy of somatostatin analogue with pegvisomant for the management of acromegaly (ESPE-ESE 2025) - "At the beginning patient received 40 mg of pasireotide. It was very effective in managing headaches. The patient continues therapy addressing both IGF-1 concentration and the most disturbing symptom."

Acromegaly • Endocrine Cancer • Endocrine Disorders • Oncology • Pain • Pituitary Gland Carcinoma • IGF1

Complete remission of headaches in aggressive PitNets treated with Pasireotide. Correlation with systemic inflammation biomarkers (SIBs). (ESPE-ESE 2025) - "Pasireotide is a second-generation SA used in acromegaly and Cushing’s disease. Nevertheless, it effectively achieves biochemical control in other PitNET subtypes and relieves headaches. Keywords: Pasireotide, Aggressive PitNets, Acromegaly, Cushing syndrome, systemic inflammation biomarkers"

Biomarker • Clinical • Acromegaly • Cushing’s Disease • Endocrine Disorders • Inflammation • Oncology • Pain • IGF1

Molecular and functional characterisation of the somatostatin system unravels novel vulnerabilities in hepatocellular carcinoma (ESPE-ESE 2025) - "Cell lines were also employed to evaluate the expression of key neuroendocrine markers and SST receptor (SSTR) downstream effectors, in addition to their functional response to SSTRs natural ligands, classic analogues (octreotide, lanreotide, pasireotide) and novel agonists (BIM-23926, BIM-23120) by different in vitro assays (proliferation, colony and hepatosphere formation)...These results could be explained through biased signalling by specific neuroendocrine markers and SSTR-downstream effectors profiles (e.g., CDH1 in Hep3B, AIP in SNU-387). In conclusion, our data suggests that the SST system is an intricate, yet exploitable source of informative biomarkers and individualised therapeutic options in HCC."

IO biomarker • Cardiovascular • Endocrine Cancer • Hepatoblastoma • Hepatocellular Cancer • Hepatology • Neuroendocrine Tumor • Oncology • Portal Hypertension • Solid Tumor • CDH1 • SSTR • SSTR2 • SSTR5

Pituitary Acrogigantism from diagnosis to effective treatment- case study (ESPE-ESE 2025) - "A second generation analogue -pasireotide were used, resulting in normalization of IGF1 and good disease control.Actually patient is a is a first-year medical student.= Conclusions Patients with pituitary acrogigantism have a heavy burden of disease and a complex treatment journey...The use of somatostatin analogues is effective in controlling GH and IGF-1 levels in patients with residual disease activity. A second generation somatostatin analogues are perspectives for patients with hard-to-control acromegaly."

Case study • Clinical • Acromegaly • Cardiovascular • Endocrine Cancer • Endocrine Disorders • Fatigue • Musculoskeletal Diseases • Musculoskeletal Pain • Oncology • Orthopedics • Otorhinolaryngology • Pain • Pituitary Gland Carcinoma • IGF1

EXPERIENCE AFTER 30 YEARS OF ACROMEGALY MANAGEMENT AT THE HOSPITAL CLÍNICO UNIVERSITARIO DE VALLADOLID (ESPE-ESE 2025) - "One year post-surgery, 29.4% were receiving Lanreotide, 8.8% Octreotide, one patient Pegvisomant, and one Pasireotide. More than half of the patients required postoperative pharmacological treatment, and some underwent radiotherapy. These findings highlight the need for a multidisciplinary approach to optimize disease control."

Clinical • Acromegaly • Endocrine Disorders • Oncology • IGF1

Phase II study to assess the efficacy and safety of pasireotide in patients with post-bariatric hypoglycaemia: PASIPHY study design (ESPE-ESE 2025) - P2 | "PASIPHY will provide valuable data on pasireotide efficacy and safety, ascertain which dose has the best benefit:risk ratio, and determine whether it is a viable treatment option for patients with PBH."

Clinical • P2 data • Gastrointestinal Disorder • Hypoglycemia • SSTR

Effective treatment of metastatic insulinoma in MEN-1 syndrom with pasireotide (ESPE-ESE 2025) - "This case highlights the complexities of managing metastatic insulinoma in the context of MEN1 syndrome. It underscores the importance of individualized treatment strategies, including receptor profiling, to guide therapy selection. While lanreotide proved ineffective, the use of pasireotide successfully controlled the patient’s hypoglycemia, emphasizing the value of alternative somatostatin analogs for SSTR5-positive tumors."

Metastases • Endocrine Cancer • Hepatology • Hypoglycemia • Neuroendocrine Tumor • Solid Tumor • SSTR2 • SSTR5

Is adrenalectomy still required as a treatment in Cushing disease? (ESPE-ESE 2025) - "In March 2020, the tumor relapse required Pasireotide 1.8 mg/day and cabergoline 1.5 mg/week increased at 8 mg/week with no biochemical or morphological response...Due to local and systemic progression of the disease, she started Temozolomide with in 2022 with no results. Since 2022 she was enrolled on Relacorilant in GRACE clinical trial (CORT125134-455) with clinical response, until June 2024. Afterwards she was treated with Metyrapone 750 mg/day, followed by Ketoconazole 800mg/day without significant improvement...Nevertheless, after the adrenalectomy, there was a noticeable improvement in biological markers. The surgery continues to represent a vital stage in the treatment journey."

Cardiovascular • Cushing’s Disease • Dermatology • Diabetes • Dyslipidemia • Growth Hormone Deficiency • Hypertension • Metabolic Disorders • Oncology • Osteoporosis • Rheumatology

management of an adrenal cortical carcinoma induced non-islet cell tumor hypoglycemia: a case report (ENDO 2025) - "She was started on adjuvant mitotane, and chemotherapy (cisplatin, etoposide, and doxorubicin) which induced cardiomyopathy...Osilodrostat was initiated for Cushing syndrome...Patient had recurrent severe hypoglycemic episodes, which were refractory to increasing carbohydrate intake, high-dose prednisone, and octreotide...She also received pasireotide 60mg and diazoxide 5mg/kg every 8 hours...Upon applying for alpelisib approval, her clinical status rapidly declined, and she died after 3 months of NITCH diagnosis...IGF2-mediated hypoglycemia was refractory to numerous therapeutic interventions, including paseriotide, pembrolizumab, olaparib, ivosidenib, and cabozantinib. This case emphasizes rare manifestations of metastatic ACC and limitations of existing medical therapies for NITCH.*. .*"

Case report • Clinical • Adrenal Cortex Carcinoma • Cardiomyopathy • Cardiovascular • Cushing’s Disease • Diabetes • Endocrine Disorders • Hematological Disorders • Hypoglycemia • Metabolic Disorders • Oncology • Pancreatic Cancer • Severe Hypoglycemia • Solid Tumor • IGF1 • IGF2

Real-World Experience with Pasireotide-LAR in Cushing's Disease: Single-Center 12-Month Observational Study. (PubMed, J Clin Med) - " Pasireotide-LAR is an effective alternative treatment in selected patients with CD. Pasireotide-LAR is overall safe and well tolerated, with hyperglycemia being the most common but manageable adverse event."

Journal • Observational data • Real-world evidence • Cushing’s Disease • Diabetes • Endocrine Cancer • Endocrine Disorders • Oncology • Pituitary Gland Carcinoma

Assessing the diagnostic, prognostic, and therapeutic potential of the somatostatin/cortistatin system in glioblastoma. (PubMed, Cell Mol Life Sci) - "Molecularly, antitumour effects of octreotide/pasireotide were exerted through key signalling-factors related to glioblastoma-aggressiveness (i.e., CDKN1A-B/JAK-STAT/NF-κB/TGF-β-pathways). Altogether, this study demonstrated that somatostatin/cortistatin-system is drastically altered in GBM representing a useful prognostic tool, and that SSTR-modulators might represent a potential therapeutic strategy to treat specific subsets of patients with GBM."

Biomarker • Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CDKN1A • CORT • EGFR • IDH1 • SSTR • SSTR2 • SSTR5 • TGFB1

Osilodrostat for Ectopic Cushing's Syndrome: A Superior Off-Label Option After Failure of Other Therapies - A Case Report (ENDO 2025) - "We present a case of ectopic CS managed with multiple medications, including metyrapone and pasireotide, with successful control ultimately achieved using osilodrostat.Clinical Case:A 76-year-old male presented with uncontrolled, new-onset diabetes mellitus (A1c: 13.5%)...A 1 mg dexamethasone suppression test (DST) revealed elevated ACTH (85 pg/mL), cortisol (16.4 µg/dL), and DHEA-S (62 µg/dL)...Osilodrostat, though off-label, is an effective and user-friendly option for managing ectopic CS, allowing for straightforward monitoring and improved patient adherence*. .*"

Case report • Clinical • Anorexia • Cushing’s Disease • Diabetes • Endocrine Cancer • Endocrine Disorders • Lung Cancer • Metabolic Disorders • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Small Cell Lung Cancer • Solid Tumor • SSTR2 • SSTR5

Managing a Resistant GH-Secreting Adenoma: A Case Report Highlighting Barriers to Patient Care (ENDO 2025) - "Post-surgery, Octreotide and Pasireotide were ineffective, the latter discontinued due to hyperglycemia...In such cases, Pegvisomant, a GH antagonist, is preferred, though it has no impact on tumor size...Physicians must adopt a patient-centered approach that includes clear communication, culturally sensitive education, and the involvement of interpreters or community resources as needed.*. .*"

Case report • Clinical • Acromegaly • Diabetes • Endocrine Disorders • Metabolic Disorders • Oncology • Pain • Pituitary Gland Carcinoma • IGF1 • SSTR