Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as SOM230
Pasireotide LAR · 9 trials · 9 indications
Percentage of participants who achieved biochemical control defined as GH \<1μg/L and IGF-1 \<ULN at week 36.
Percentage of participants who achieved biochemical control defined as GH \<1μg/L and IGF-1 \<ULN at week 36, for participants who had been up-titrated with pasireotide LAR 60 mg.
Percentage of participants who achieved biochemical control defined as GH \<1μg/L and IGF-1 \<ULN at week 36.
Percentage of participants who achieved biochemical control defined as GH \<1μg/L and IGF-1 \<ULN at week 36, overall by baseline diabetic status.
Percentage of participants who achieved biochemical control defined as GH \<1μg/L and IGF-1 \<ULN at week 36, by previous treatment and overall - last observation carried forward (LOCF)
Percentage of participants that attained a mean urinary free cortisol (mUFC) \<= 1.0 x upper limit of normal (ULN) at Month 7 regardless of dose up-titration at Month 4. Patients who discontinued before month 4 evaluations classed as non-responders. For patients missing month 7 mUFC assessments, the last available mUFC assessment at or after month 4 was carried forward as the month 7 mUFC assessment value.
Patients with Complete Response (CR), Partial Response (PR), or Stable Disease (SD) at Month 9 were to be considered as "progression-free" based on RECIST v1.1. Patients with missing tumor assessment, or with overall lesion response "unknown" at Month 9 were considered as "non progression-free", unless any of the following assessments at Week 48 or Week 52 indicate CR, PR, or SD, in which case the patient was to be considered as progression-free at Month 9. Patients discontinuing the study for any reason prior to the 9 month assessment were to be considered as "non progression-free".
Response rate is defined as percentage of patients with no glucose values \< 60 mg/dL at 90,120, 150 and 180 min during the Oral Glucose Tolerance Test (OGTT) at the end of s.c. dose escalation phase
Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility.The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor. A change ≥ 20% in the original volume of the tumor was considered to be clinically significant. Evaluable participants required tumor volume assessment at baseline and at week 24.
Percentage of participants with a reduction of mean growth hormone (GH) levels to \< 2.5 µg/L and the normalization of insulin-like growth factor-1 (IGF-1) to within normal limits (age and sex related) at 3 months across all doses
DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications as defined per study prototol. These will be evaluated according to the CTCAE v4.03.
Progression is defined as a PSA-increase of at least 25% and an absolute increase of at least 2 ng/ml from a nadir value, confirmed by a second value four weeks later.
Description: Cmax, AUCinf, AUClast, CL/F, CLR, glucose, insulin, glucagon
Frequency of dose-limiting toxicities (DLTs) at each dose level associated with q28 days administration of pasireotide LAR during the first 2 treatment cycles.
| Arm | Type | Description |
|---|---|---|
| Pasireotide LAR | EXPERIMENTAL | Patients who qualify for the core phase of the study will be treated with pasireotide LAR 40 mg initially. Patients not achieving biochemical control can be up-titrated to pasireotide LAR 60 mg. |
| 10 mg LAR dose | EXPERIMENTAL | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. |
| 30 mg LAR dose | EXPERIMENTAL | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. |
| Everolimus | EXPERIMENTAL | Everolimus 10 mg taken orally (p.o) once daily starting on Day 1 |
| Pasireotide LAR and Everolimus Combination | EXPERIMENTAL | Pasireotide LAR 60 mg i.m. injected once every 28 days + Everolimus 10 mg p.o. daily starting on Day 1 |
| SOM230 | EXPERIMENTAL | Subjects with dumping syndrome treated with pasireotide |
| Pasireotide LAR 20mg | EXPERIMENTAL | Enrolled patients were randomized to 20mg pasireotide LAR. |
| Pasireotide LAR 40mg | EXPERIMENTAL | Enrolled patients were randomized to 40mg pasireotide LAR. |
| Pasireotide LAR 60mg | EXPERIMENTAL | Enrolled patients were randomized to 60mg pasireotide LAR. |
| Name | Type | Description |
|---|---|---|
| Pasireotide LAR | DRUG | Pasireotide 40 mg and 60 mg. Pasireotide 20 mg which was allowed for dose decrease in case of adverse event. |
| SOM230 LAR 30 mg | DRUG | starting dose of 30 mg i.m. administered once every 28 days for 4 months, followed by dose up-titration or continuation of starting dose. |
| SOM230 LAR 10 mg | DRUG | starting does of SOM230 LAR 10 mg i.m. administered once every 28 days for 4 months, followed by dose up-titration or continuation of the starting dose. |
| Everolimus | DRUG | 10 mg tables administered orally once a day |
| Pasireotide LAR and Everolimus Combination | DRUG | Pasireotide LAR 60 mg i.m. injected once every 28 days + Everolimus 10 mg p.o. daily |
| SOM230 | DRUG | Pasireotide (SOM230) sc injection was provided as solution for injection in individual 1-point-cut 1 mL ampule, containing nominally 200 μg of pasireotide (as free base). Doses: 50, 100, 150 and 200 μg. Pasireotide im LAR depot injection was provided as micro particles powder in vials containing nominally 10, 20, 40 \& 60 mg of pasireotide (as free base) \& solvent for suspension for injection in ampules for the reconstitution of the LAR micro particles. Doses: 10, 20, 30, 40 or 60 mg |
Inclusion Criteria: * Written informed consent * Male and female patients ≥18 years * Patients with confirmed diagnosis of inadequately controlled acromegaly (mean GH concentration ≥1 μg/L and sex- and age-adjusted IGF-1 \>1.3 x ULN) * Patients treated with octreotide LAR (30 mg or 40 mg) or lanreo...
Pasireotide LAR is used to treat acromegaly, Cushing's disease, neuroendocrine carcinoma of the lung and thymus, neuroendocrine tumors, and non-functioning pituitary adenoma. It is a long-acting release formulation developed by Novartis AG and studied across these endocrine and neuroendocrine conditions.
Pasireotide LAR targets somatostatin receptors SSTR1, SSTR2, SSTR3, and SSTR5, acting as an agonist at these receptors. Binding to these receptors is the mechanism by which the drug is designed to reduce hormone secretion in conditions such as acromegaly and Cushing's disease.
Pasireotide LAR is developed by Novartis AG, which trades under the ticker NVS. Novartis is the sponsor of the clinical trials evaluating the long-acting release formulation in acromegaly, Cushing's disease, and neuroendocrine tumors.
Pasireotide LAR has been studied in Phase 3 clinical development, including a Phase 3 trial in acromegaly and a Phase 3 trial in Cushing's disease. It is an investigational agent in the trials described here and remains under clinical evaluation for its listed indications.
Pasireotide LAR has been evaluated in completed trials including NCT02354508 in acromegaly, NCT01374906 in Cushing's disease, NCT01673646 in acromegaly and pituitary gigantism, and NCT01563354, the LUNA trial, in lung and thymus neuroendocrine carcinoma. These studies enrolled patients across multiple countries.
Pasireotide LAR is also known as Signifor LAR, the long-acting release formulation of pasireotide. Both names refer to the same Novartis compound, which targets somatostatin receptors SSTR1, SSTR2, SSTR3, and SSTR5 and has been studied in acromegaly, Cushing's disease, and neuroendocrine tumors.