CLINICAL TRIALS PROFILE FOR SYLVANT

All Clinical Trials for SYLVANT

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02796859 ↗	Siltuximab in Schizophrenia	Recruiting	Stanley Medical Research Institute	Phase 1/Phase 2	2016-05-01	This study is a Phase 1 clinical trial to determine the safety, tolerability, and efficacy of Siltuximab (Sylvant) as an adjunct to antipsychotic medications in stable outpatients with schizophrenia. Siltuximab (structural formula C6450H9932N1688O2016S50) is a recombinant chimeric (human-murine) anti-human interleukin-6 (IL-6) monoclonal antibody. Siltuximab is formulated as a concentrate for solution for infusion, and will be administered by intravenous infusion. The investigators propose a 9-week randomized controlled trial of siltuximab, given in adjunct to antipsychotics, in N=30 stable outpatients with schizophrenia or schizoaffective disorder and evidence of increased inflammation in the peripheral blood (high-sensitivity C-reactive protein [hsCRP] >0.5 mg/dL). The investigators hypothesize that adjunctive treatment with siltuximab will be associated with significant improvement in cognition compared to placebo in patients with schizophrenia, baseline IL-6 levels are higher in siltuximab-treated responders versus non-responders, and there will be greater decreases in hsCRP from baseline to week 6 in siltuximab-treated versus placebo-treated responders, with response defined as ≥0.5 SD improvement in cognition. Siltuximab is administered as an intravenous infusion every 3 weeks. Following a screening evaluation, participants will receive three infusions of siltuximab, one at baseline, another at week 3 of the study, and another at week 6. The investigators will measure changes in cognitive function and symptoms over a 9-week period. Complementing previous positive clinical trials of non-steroidal anti-inflammatory drugs, this would be a "proof-of-concept" study that targeting specific cytokines is a viable treatment for schizophrenia. Interleukin 6 and its receptor were discovered and cloned at Osaka University, Japan, by Tadamitsu Kishimoto in the 1980s. Janssen Pharmaceuticals, Inc. began the clinical development of siltuximab for the treatment of multicentric Castleman's disease, a rare blood disorder. Other clinical studies with siltuximab have been conduced for patients with B-cell non-Hodgkin's lymphoma, multiple myeloma, and ovarian cancer. In April 2014,siltuxiumab was approved by the U.S. Food and Drug Administration (US FDA) as Sylvant for human immunodeficiency virus (HIV)-negative and human herpesvirus-8 (HHV-8)-negative multicentric Castleman's disease.
NCT02796859 ↗	Siltuximab in Schizophrenia	Recruiting	Brian Miller	Phase 1/Phase 2	2016-05-01	This study is a Phase 1 clinical trial to determine the safety, tolerability, and efficacy of Siltuximab (Sylvant) as an adjunct to antipsychotic medications in stable outpatients with schizophrenia. Siltuximab (structural formula C6450H9932N1688O2016S50) is a recombinant chimeric (human-murine) anti-human interleukin-6 (IL-6) monoclonal antibody. Siltuximab is formulated as a concentrate for solution for infusion, and will be administered by intravenous infusion. The investigators propose a 9-week randomized controlled trial of siltuximab, given in adjunct to antipsychotics, in N=30 stable outpatients with schizophrenia or schizoaffective disorder and evidence of increased inflammation in the peripheral blood (high-sensitivity C-reactive protein [hsCRP] >0.5 mg/dL). The investigators hypothesize that adjunctive treatment with siltuximab will be associated with significant improvement in cognition compared to placebo in patients with schizophrenia, baseline IL-6 levels are higher in siltuximab-treated responders versus non-responders, and there will be greater decreases in hsCRP from baseline to week 6 in siltuximab-treated versus placebo-treated responders, with response defined as ≥0.5 SD improvement in cognition. Siltuximab is administered as an intravenous infusion every 3 weeks. Following a screening evaluation, participants will receive three infusions of siltuximab, one at baseline, another at week 3 of the study, and another at week 6. The investigators will measure changes in cognitive function and symptoms over a 9-week period. Complementing previous positive clinical trials of non-steroidal anti-inflammatory drugs, this would be a "proof-of-concept" study that targeting specific cytokines is a viable treatment for schizophrenia. Interleukin 6 and its receptor were discovered and cloned at Osaka University, Japan, by Tadamitsu Kishimoto in the 1980s. Janssen Pharmaceuticals, Inc. began the clinical development of siltuximab for the treatment of multicentric Castleman's disease, a rare blood disorder. Other clinical studies with siltuximab have been conduced for patients with B-cell non-Hodgkin's lymphoma, multiple myeloma, and ovarian cancer. In April 2014,siltuxiumab was approved by the U.S. Food and Drug Administration (US FDA) as Sylvant for human immunodeficiency virus (HIV)-negative and human herpesvirus-8 (HHV-8)-negative multicentric Castleman's disease.
NCT02641522 ↗	Modulation of STAT3 Signaling With Siltuximab in Type 1 Diabetes	Completed	Janssen Research & Development, LLC	Early Phase 1	2016-03-08	The purpose of this study is to evaluate the effects of siltuximab on immune cell functions in patients with Type 1 diabetes (T1D).
NCT02641522 ↗	Modulation of STAT3 Signaling With Siltuximab in Type 1 Diabetes	Completed	Carla Greembaum, MD	Early Phase 1	2016-03-08	The purpose of this study is to evaluate the effects of siltuximab on immune cell functions in patients with Type 1 diabetes (T1D).
NCT02641522 ↗	Modulation of STAT3 Signaling With Siltuximab in Type 1 Diabetes	Completed	Carla Greenbaum, MD	Early Phase 1	2016-03-08	The purpose of this study is to evaluate the effects of siltuximab on immune cell functions in patients with Type 1 diabetes (T1D).

Clinical Trial Conditions for SYLVANT

Condition Name

Condition Name for SYLVANT
Intervention	Trials
Schwannomatosis	1
Acute Respiratory Distress Syndrome	1
Type 1 Diabetes	1
Idiopathic Multicentric Castleman's Disease	1

Condition MeSH

Condition MeSH for SYLVANT
Intervention	Trials
Acute Lung Injury	1
Respiratory Tract Infections	1
Skin Neoplasms	1
Schizophrenia	1

Clinical Trial Locations for SYLVANT

Trials by Country

+

−

Trials by Country for SYLVANT
Location	Trials
United States	6

Trials by US State

+

−

Trials by US State for SYLVANT
Location	Trials
Michigan	2
Georgia	1
Washington	1
Massachusetts	1
North Carolina	1

Clinical Trial Progress for SYLVANT

Clinical Trial Phase

Clinical Trial Phase for SYLVANT
Clinical Trial Phase	Trials
Phase 3	1
Phase 2	2
Phase 1/Phase 2	1

Clinical Trial Status

Clinical Trial Status for SYLVANT
Clinical Trial Phase	Trials
Terminated	2
Completed	1
Not yet recruiting	1

Clinical Trial Sponsors for SYLVANT

Sponsor Name

Sponsor Name for SYLVANT
Sponsor	Trials
EusaPharma (UK) Limited	2
Carla Greenbaum, MD	1
Stanley Medical Research Institute	1

Sponsor Type

Sponsor Type for SYLVANT
Sponsor	Trials
Other	6
Industry	4
U.S. Fed	1

SYLVANT (Siltuximab): Clinical Trials, Market Analysis, and Projections

Introduction to SYLVANT

SYLVANT (siltuximab) is a monoclonal antibody that has made significant strides in the treatment of idiopathic multicentric Castleman’s disease (iMCD), a rare and debilitating condition. Here, we will delve into the clinical trials that led to its approval, its current market position, and future projections.

Clinical Trials Overview

MCD2001 Pivotal Study

The efficacy and safety of SYLVANT were evaluated in the MCD2001 study, a multinational, randomized, double-blind, placebo-controlled trial. This study involved 79 patients with symptomatic iMCD who were HIV and HHV-8 negative. Patients were randomized to receive either SYLVANT at a dose of 11 mg/kg or a placebo, both in combination with best supportive care (BSC)[3][4].

Key Efficacy Measures

• Durable Tumor and Symptomatic Response: More than one-third of patients in the SYLVANT arm achieved a durable tumor and symptomatic response, defined as a response that persisted for at least 18 weeks without treatment failure. This was in stark contrast to the placebo arm, where no patients achieved such a response (34% vs 0%, p=0.0012)[3][4].
• Tumor Response Rate: The tumor response rate was significantly higher in the SYLVANT arm, with 38% of patients showing a response compared to 4% in the placebo arm[3].
• Median Time to Treatment Failure: The median time to treatment failure was not reached for patients receiving SYLVANT plus BSC, while those receiving placebo plus BSC experienced treatment failure at a median of 134 days (p<0.05)[3].

Market Analysis

Approval and Regulatory Status

SYLVANT received FDA approval in April 2014 for the treatment of iMCD, marking the first approved treatment for this condition in the United States. It was also granted orphan product designation due to its focus on a rare disease. Similar approvals followed in the European Union, the Republic of Korea, Canada, and over 40 other countries worldwide[2][3][4].

Acquisition and Ownership

In 2018, EUSA Pharma acquired the global rights to SYLVANT from Janssen Sciences Ireland UC for $115 million. This acquisition significantly boosted EUSA Pharma’s presence in the oncology and rare disease markets, aligning with their strategy to address unmet patient needs[2][5].

Market Performance

Since its approval, SYLVANT has seen rapid revenue growth. Although J&J does not break out sales figures for SYLVANT, EUSA Pharma has highlighted the drug's commercial success. The acquisition by EUSA Pharma is expected to further enhance the drug's market presence and revenue potential[2][5].

Current and Future Indications

Idiopathic Multicentric Castleman’s Disease (iMCD)

SYLVANT remains the only FDA and EMA-approved treatment for iMCD, a condition characterized by the abnormal overgrowth of immune cells and symptoms similar to lymphoma. The drug's efficacy in this area has been well-documented, providing significant relief to patients with limited treatment options[2][3].

Other Indications

• Renal Cell Carcinoma, Non-Hodgkin Lymphoma, Prostate Cancer, and Type 1 Diabetes: SYLVANT has been studied in these indications, though it is not yet approved for these uses[2][5].
• High-Risk Smoldering Multiple Myeloma: The drug is undergoing active assessment in this area, potentially expanding its therapeutic scope[2][5].
• Cytokine Release Syndrome (CRS): SYLVANT is being investigated as an immunosuppressive agent to alleviate symptoms of CRS, a serious side effect of CAR-T cell therapies[2][5].

Market Projections

Growth Potential

Given its unique position as the only approved treatment for iMCD and its potential in other indications, SYLVANT is poised for continued growth. EUSA Pharma’s expertise in commercializing rare disease treatments is expected to drive further market penetration and revenue increases.

Competitive Landscape

The rare disease market, particularly for iMCD, has limited competition, which favors SYLVANT’s market dominance. However, ongoing research in related conditions and the potential emergence of new treatments could impact its market share in the future.

Regulatory and Market Exclusivity

SYLVANT benefits from Orphan Market Exclusivity in both the United States and Europe, protecting its market position for several years. This exclusivity, combined with its strong clinical data, ensures a stable market presence[2][3].

Challenges and Opportunities

Diagnostic Challenges

iMCD is often misdiagnosed due to its similarity to other conditions like lymphoma and autoimmune disorders. Improving diagnostic tools and awareness could increase the patient pool and subsequently drive demand for SYLVANT[5].

Expanding Indications

The ongoing studies in various other indications offer significant opportunities for SYLVANT to expand its therapeutic scope and market reach. Success in these areas could substantially increase its revenue potential.

Key Takeaways

• Clinical Efficacy: SYLVANT has demonstrated significant efficacy in treating iMCD, with durable tumor and symptomatic responses observed in clinical trials.
• Market Position: It is the only approved treatment for iMCD globally, with a strong market presence and rapid revenue growth.
• Future Indications: Ongoing studies in other conditions such as renal cell carcinoma, non-Hodgkin lymphoma, and high-risk smoldering multiple myeloma could expand its therapeutic use.
• Market Projections: With Orphan Market Exclusivity and EUSA Pharma’s commercial expertise, SYLVANT is projected to continue its growth trajectory.

FAQs

What is SYLVANT used for?

SYLVANT (siltuximab) is used for the treatment of idiopathic multicentric Castleman’s disease (iMCD), a rare and debilitating condition.

Who owns the global rights to SYLVANT?

EUSA Pharma acquired the global rights to SYLVANT from Janssen Sciences Ireland UC in 2018.

What were the key findings of the MCD2001 study?

The MCD2001 study showed that more than one-third of patients treated with SYLVANT achieved a durable tumor and symptomatic response, with a significant difference in tumor response rates and median time to treatment failure compared to the placebo group.

Is SYLVANT being studied for other indications?

Yes, SYLVANT is being studied for other indications including renal cell carcinoma, non-Hodgkin lymphoma, prostate cancer, type 1 diabetes, and high-risk smoldering multiple myeloma.

What is the current market status of SYLVANT?

SYLVANT has seen rapid revenue growth since its approval and is expected to continue growing under EUSA Pharma’s commercial strategy.

Sources

1. Study Design - SYLVANT® (siltuximab). Sylvant.
2. EUSA Pharma Announces Acquisition of Global Rights to SYLVANT .... Biospace.
3. SYLVANT™ (siltuximab) Receives FDA Approval to Treat .... Johnson & Johnson.
4. Siltuximab (Sylvant) - Medical Clinical Policy Bulletins - Aetna. Aetna.
5. Eusa acquires rights to J&J rare disease drug Sylvant. Biopharma Dive.