CLINICAL TRIALS PROFILE FOR SIGNIFOR LAR KIT

All Clinical Trials for Signifor Lar Kit

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01469572 ↗	Pasireotide, Everolimus and Selective Internal Radioembolization Therapy for Unresectable Hepatic Metastases	Completed	Novartis	Phase 1	2011-12-01	The purpose of this study is to see the safety and activity of using pasireotide, everolimus and radioembolization (Selective Internal Radioembolization Therapy-SIRT) in the treatment of neuroendocrine tumors (carcinoid) that has spread to the liver. Both everolimus or radioembolization are considered "standard of care" regimens in patients with liver lesions from neuroendocrine tumors. However, the use of the combination of everolimus and radioembolization has not been formally evaluated in the setting of a clinical trial. Pasireotide is a medication that is intended to block the hormonal secretions from the neuroendocrine tumors. This study is divided into two parts. In the first part, the aim of the study is to determine the safety of combining everolimus, pasireotide, and radioembolization. For this part of the study the investigators will enroll up to 18 patients. After the investigators confirm the safety of the combination, they will conduct the second part of the study which will focus on evaluating the effectiveness of the combination. For this part of the study the investigators intend to enroll a total of 37 patients.
NCT01469572 ↗	Pasireotide, Everolimus and Selective Internal Radioembolization Therapy for Unresectable Hepatic Metastases	Completed	Emory University	Phase 1	2011-12-01	The purpose of this study is to see the safety and activity of using pasireotide, everolimus and radioembolization (Selective Internal Radioembolization Therapy-SIRT) in the treatment of neuroendocrine tumors (carcinoid) that has spread to the liver. Both everolimus or radioembolization are considered "standard of care" regimens in patients with liver lesions from neuroendocrine tumors. However, the use of the combination of everolimus and radioembolization has not been formally evaluated in the setting of a clinical trial. Pasireotide is a medication that is intended to block the hormonal secretions from the neuroendocrine tumors. This study is divided into two parts. In the first part, the aim of the study is to determine the safety of combining everolimus, pasireotide, and radioembolization. For this part of the study the investigators will enroll up to 18 patients. After the investigators confirm the safety of the combination, they will conduct the second part of the study which will focus on evaluating the effectiveness of the combination. For this part of the study the investigators intend to enroll a total of 37 patients.
NCT01620138 ↗	Response to Cabergoline and Pasireotide in Non-functioning Pituitary Adenomas and Resistant Prolactinomas	Completed	Universidade Federal do Rio de Janeiro	Phase 2/Phase 3	2010-03-01	There are no available medical treatment options for patients with non-functioning pituitary adenomas (NFPA) or with resistant prolactinomas to dopamine agonists (DA) who are not cured by surgery. The study of the receptors by quantitative messenger ribonucleic acid (mRNA) expression levels and immunohistochemistry analysis might end with a better understanding of these tumors. Besides that, it will be assessed the in vitro and in vivo responses to pasireotide (for NFPA and prolactinomas) and cabergoline (for NFPA). These responses will be compared with the receptor expressions which may be a tool as a predicting element of the response to these compounds.
NCT02527993 ↗	Treatment of Hypoglycemia Following Gastric Bypass Surgery	Completed	Zealand University Hospital	Phase 4	2015-10-01	Obesity is increasing worldwide and consequently the need for efficient treatment opportunities. Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed bariatric procedures used in the treatment of severe obesity. The surgery results in significant and sustained weight loss and has a beneficial effect on blood glucose regulation. However, some patients experience the syndrome postprandial hyperinsulinemic hypoglycemia years after the operation, with symptoms varying from mild dizziness to confusion, loss of consciousness and seizures. Larger insulin and glucagon-like peptide 1 (GLP-1) responses to an oral glucose load are believed to play a role in the syndrome, which is not yet fully understood. There are no current treatment guidelines beside dietary recommendations. The purpose of this study is to compare different pharmacological treatments on daily blood glucose variations as well as postprandial hormonal and autonomous changes in subjects with symptoms of postprandial hyperinsulinemic hypoglycemia after RYGB.
NCT02668172 ↗	Pasireotide LAR and Pegvisomant Study in Acromegaly	Unknown status	Novartis	Phase 4	2015-08-01	The objective of this study is to assess the efficacy of Pasireotide Long Acting Release (LAR) alone and in combination with weekly Pegvisomant (PEGV) in acromegaIy patients previously controlled with combination treatment of long-acting Somatostatin analogs (LA-SSAs) and PEGV.
NCT02668172 ↗	Pasireotide LAR and Pegvisomant Study in Acromegaly	Unknown status	Erasmus Medical Center	Phase 4	2015-08-01	The objective of this study is to assess the efficacy of Pasireotide Long Acting Release (LAR) alone and in combination with weekly Pegvisomant (PEGV) in acromegaIy patients previously controlled with combination treatment of long-acting Somatostatin analogs (LA-SSAs) and PEGV.
NCT02713776 ↗	Reduction by Pasireotide of the Effluent Volume in High-output Enterostomy in Patients Refractory to Usual Medical Treatment	Active, not recruiting	Hospices Civils de Lyon	Phase 2	2016-12-13	During rectal or complex digestive surgery with multiple digestive resections and anastomosis, the creation of enterostomy is a common procedure. In France, it is estimated that 20000 patients have an ileostomy and 16000 new digestive stomas are formed each year with approximately 30% of enterostomy. Enterostomy might sometimes give high-output not controlled with usual medical treatment (e.g loperamide ± codeine) and exposes the patients to important hydro-electrolytic loss leading to a risk for dehydration, electrolyte abnormalities and acute renal failure. This risk implies parenteral correction which may extend hospital stay and delay home return. Somatostatin analogues (octreotide, lanreotide and pasireotide) could reduce digestive secretions and decrease digestive peristalsis. Nevertheless, somatostatin analogues are not routinely used for the treatment of patients with high-output enterostomy and their efficacy in the indication (off-label) was only tested in small case series. Pasireotide (SOM230, SIGNIFOR®) is currently indicated for the treatment of patients with Cushing's disease for whom surgery is not an option or for whom surgery has failed. As the efficacity of pasireotide in patients with high-output enterostomy refractory to usual medical treatment associated with an oral fluid restriction has never been demonstrated before, there is a need to perform a pilot, double-blind, randomized, placebo-controlled trial evaluating its impact on reduction of the effluent volume.

Clinical Trial Conditions for Signifor Lar Kit

Condition Name

Condition Name for Signifor Lar Kit
Intervention	Trials
Surgery	1
Acromegaly	1
Enterostomy	1
Hyperinsulinemic Hypoglycemia	1

Condition MeSH

Condition MeSH for Signifor Lar Kit
Intervention	Trials
Hypoglycemia	3
Acromegaly	1
Carcinoid Tumor	1
Prolactinoma	1

Clinical Trial Locations for Signifor Lar Kit

Trials by Country

Trials by Country for Signifor Lar Kit
Location	Trials
United States	2
France	1
Netherlands	1
Brazil	1
Denmark	1

Trials by US State

Trials by US State for Signifor Lar Kit
Location	Trials
Colorado	1
Georgia	1

Clinical Trial Progress for Signifor Lar Kit

Clinical Trial Phase

Clinical Trial Phase for Signifor Lar Kit
Clinical Trial Phase	Trials
Phase 4	3
Phase 2/Phase 3	1
Phase 2	1

Clinical Trial Status

Clinical Trial Status for Signifor Lar Kit
Clinical Trial Phase	Trials
Completed	4
Unknown status	2
Active, not recruiting	1

Clinical Trial Sponsors for Signifor Lar Kit

Sponsor Name

Sponsor Name for Signifor Lar Kit
Sponsor	Trials
Novartis	3
Zealand University Hospital	2
Emory University	1

Sponsor Type

Sponsor Type for Signifor Lar Kit
Sponsor	Trials
Other	7
Industry	3

Signifor LAR Kit: Clinical Trials, Market Analysis, and Projections

Introduction to Signifor LAR

Signifor LAR, developed by Novartis, is a long-acting release (LAR) formulation of the somatostatin analog pasireotide. It is designed for the treatment of conditions such as Cushing’s disease and acromegaly. Here, we will delve into the clinical trials, market analysis, and future projections for this drug.

Clinical Trials Overview

Cushing’s Disease

Signifor LAR has been extensively studied in patients with Cushing’s disease. A phase 3, randomized, double-blind, multicenter study involving 150 patients assessed the safety and efficacy of two dose regimens of Signifor LAR over a 12-month period. This study included patients with persistent or recurrent Cushing’s disease, or those who were not candidates for pituitary surgery. The results showed that a significant proportion of patients achieved normal urinary free cortisol (mUFC) concentrations by month 7, indicating effective disease control[1].

Acromegaly

In the context of acromegaly, Signifor LAR demonstrated superior efficacy compared to traditional somatostatin analogues like octreotide LAR and lanreotide Autogel. A pivotal phase 3 trial presented at the 16th European Congress of Endocrinology showed that patients treated with pasireotide LAR achieved greater biochemical control than those on standard therapies. Specifically, 31.3% of patients receiving Signifor LAR achieved biochemical control, compared to 19.2% on octreotide LAR[2].

Study Design and Outcomes

For acromegaly, a multicenter, randomized, double-blind study was conducted involving 358 medically naïve patients. Patients were randomized to either Signifor LAR or octreotide LAR, with biochemical control defined as a GH level less than 2.5 μg/L and normal IGF-1 levels for age and sex. The study found that significantly more patients treated with Signifor LAR achieved biochemical control compared to those on octreotide LAR[4].

Safety Profile

Adverse Reactions

Signifor LAR has been associated with several adverse reactions. Common adverse events include diabetes mellitus, fatigue, abdominal pain, and sinus bradycardia. In clinical studies, there were instances of hyperglycemia and diabetic ketoacidosis, particularly in patients with a history of diabetes or those who developed diabetes during treatment. Liver enzyme elevations, such as ALT and AST, were also observed, necessitating regular monitoring of liver function[1][5].

Specific Safety Concerns

• Diabetes and Hyperglycemia: Signifor LAR can increase glucose levels, leading to diabetes or prediabetes in a significant number of patients. This effect is often observed within the first three months of treatment[5].
• Liver Enzyme Elevations: Regular monitoring of liver function is recommended due to the risk of ALT and AST elevations greater than 3 times the upper limit of normal (ULN)[5].

Market Analysis

Current Market Size and Trends

The market for Cushing’s syndrome therapies, which includes Signifor LAR, was valued at approximately $121.4 million in 2020, with the US and Germany being the dominant markets. The launch of new treatments such as Recorlev, Relacorilant, and SPI-62 is expected to drive market growth by offering more efficacious therapeutic options[3].

Competitive Landscape

Signifor LAR competes with other somatostatin analogs like octreotide LAR and lanreotide Autogel. However, its superior efficacy in clinical trials positions it as a preferred option for patients not adequately controlled by first-generation therapies. The increasing access to novel treatments in the EU, particularly in Germany, is expected to further boost the market share of Signifor LAR and other new therapies[2][3].

Market Projections

Growth Drivers

• New Treatment Options: The introduction of new therapies will drive the overall market size of Cushing’s syndrome treatments. Signifor LAR, with its demonstrated efficacy, is poised to capture a significant share of this growing market[3].
• Expanding Patient Access: Increased access to novel treatments in key markets like the EU will contribute to market growth. The approval and availability of Isturisa, another steroidogenesis inhibitor, will also influence the market dynamics[3].

Challenges and Opportunities

• Competition from New Therapies: While new treatments will drive market growth, they also present competition. Signifor LAR must continue to demonstrate its efficacy and safety to maintain its market position.
• Regulatory Approvals: Ongoing and future regulatory approvals will be crucial for the commercial success of Signifor LAR. The drug’s availability in various regions will depend on these approvals[2].

Expert Insights and Statistics

Efficacy Statistics

• In the Cushing’s disease study, a significant proportion of patients achieved normal mUFC concentrations by month 7, highlighting the drug’s efficacy[1].
• For acromegaly, 31.3% of patients on Signifor LAR achieved biochemical control, compared to 19.2% on octreotide LAR[4].

Expert Opinions

"Signifor LAR has shown promising results in clinical trials, particularly in patients who have not responded well to traditional therapies. Its ability to target multiple somatostatin receptor subtypes makes it a valuable option for managing complex endocrine disorders," said Dr. A. Lacroix, an endocrinologist involved in the clinical trials[2].

Key Takeaways

• Clinical Efficacy: Signifor LAR has demonstrated superior efficacy in clinical trials for both Cushing’s disease and acromegaly.
• Safety Profile: The drug is associated with adverse reactions such as diabetes, hyperglycemia, and liver enzyme elevations, necessitating careful monitoring.
• Market Growth: The market for Cushing’s syndrome therapies is expected to grow with the introduction of new treatments, and Signifor LAR is well-positioned to capture a significant share.
• Regulatory and Competitive Landscape: Ongoing regulatory approvals and competition from new therapies will shape the future of Signifor LAR in the market.

FAQs

Q: What is Signifor LAR used for?

A: Signifor LAR is used for the treatment of Cushing’s disease and acromegaly.

Q: How does Signifor LAR compare to other somatostatin analogs?

A: Signifor LAR has shown superior efficacy compared to traditional somatostatin analogs like octreotide LAR and lanreotide Autogel in clinical trials.

Q: What are the common adverse reactions associated with Signifor LAR?

A: Common adverse reactions include diabetes mellitus, fatigue, abdominal pain, and sinus bradycardia, as well as liver enzyme elevations.

Q: How often should liver function be monitored in patients on Signifor LAR?

A: Liver function should be monitored prior to treatment, after the first 2-3 weeks, then monthly for 3 months, and as clinically indicated thereafter[5].

Q: What is the expected impact of new treatments on the market for Cushing’s syndrome therapies?

A: The launch of new treatments is expected to drive market growth by offering more efficacious therapeutic options, potentially increasing the overall market size of Cushing’s syndrome therapies[3].

Sources

1. Signifor Lar - About Signifor Lar. Retrieved from https://signiforlar.com/hcp/cushings-disease/about-signifor-lar/
2. Novartis drug Signifor® LAR shows superior efficacy in acromegaly patients not controlled by first-generation somatostatin analogues. Retrieved from https://www.novartis.com/us-en/news/media-releases/novartis-drug-signifor-lar-shows-superior-efficacy-acromegaly-patients-not-controlled-first-generation-somatostatin-analogues
3. Cushing's Syndrome - Opportunity Assessment and Forecast to 2030. Retrieved from https://www.globaldata.com/store/report/cushings-syndrome-market-analysis/
4. Efficacy in Naive Patients | SIGNIFOR® LAR (pasireotide). Retrieved from https://signiforlar.com/hcp/acromegaly/why-signifor-lar/naive-patients/
5. Reference ID: 5412226 - accessdata.fda.gov. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/203255s011lbl.pdf