CLINICAL TRIALS PROFILE FOR SIROLIMUS

505(b)(2) Clinical Trials for Sirolimus

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Combination	NCT00565773 ↗	Belatacept Post Depletional Repopulation to Facilitate Tolerance	Completed	Bristol-Myers Squibb	Phase 2	2007-12-01	Acute rejection is a common problem after a kidney transplant. Rejection can occur when the kidney recipient's immune system tries to attack (or reject) the new kidney. Rejection typically most often develops in the first few months after a transplant. This single center study will seek to determine if a new combination of anti-rejection medications, including the recently FDA approved drug called Belatacept, is better than the current standard anti-rejection drug regimen at preventing rejection. Also to be determined will be whether the new combination of drugs will allow participants to wean off their oral anti-rejection medications over time. This study will test the safety and effectiveness of a new investigational drug combination using alemtuzumab, belatacept, and sirolimus when given with or without donor bone marrow. This combination of medicines has not been tested before in humans. Alemtuzumab (Campath) is approved for use in some types of white blood cell cancers, but is considered investigational in transplant patients. Belatacept is now FDA approved and is being studied in transplant patients. Sirolimus (Rapamune) is approved for use in transplant patients, but its use with belatacept and alemtuzumab is investigational. In the initial 20 subjects enrolled in the study, half tested whether an infusion of bone marrow from the kidney donor would improve the effect of these drugs. This bone marrow infusion was also considered investigational. Enrollment of 20 additional subjects began in January, 2013. The donor bone marrow infusion has been eliminated. Enrollment was open to primary living and deceased donor kidney recipients. Enrollment was closed as of 8/12/2014.
New Combination	NCT00565773 ↗	Belatacept Post Depletional Repopulation to Facilitate Tolerance	Completed	Duke University	Phase 2	2007-12-01	Acute rejection is a common problem after a kidney transplant. Rejection can occur when the kidney recipient's immune system tries to attack (or reject) the new kidney. Rejection typically most often develops in the first few months after a transplant. This single center study will seek to determine if a new combination of anti-rejection medications, including the recently FDA approved drug called Belatacept, is better than the current standard anti-rejection drug regimen at preventing rejection. Also to be determined will be whether the new combination of drugs will allow participants to wean off their oral anti-rejection medications over time. This study will test the safety and effectiveness of a new investigational drug combination using alemtuzumab, belatacept, and sirolimus when given with or without donor bone marrow. This combination of medicines has not been tested before in humans. Alemtuzumab (Campath) is approved for use in some types of white blood cell cancers, but is considered investigational in transplant patients. Belatacept is now FDA approved and is being studied in transplant patients. Sirolimus (Rapamune) is approved for use in transplant patients, but its use with belatacept and alemtuzumab is investigational. In the initial 20 subjects enrolled in the study, half tested whether an infusion of bone marrow from the kidney donor would improve the effect of these drugs. This bone marrow infusion was also considered investigational. Enrollment of 20 additional subjects began in January, 2013. The donor bone marrow infusion has been eliminated. Enrollment was open to primary living and deceased donor kidney recipients. Enrollment was closed as of 8/12/2014.
New Combination	NCT00565773 ↗	Belatacept Post Depletional Repopulation to Facilitate Tolerance	Completed	Allan D Kirk, MD, PhD	Phase 2	2007-12-01	Acute rejection is a common problem after a kidney transplant. Rejection can occur when the kidney recipient's immune system tries to attack (or reject) the new kidney. Rejection typically most often develops in the first few months after a transplant. This single center study will seek to determine if a new combination of anti-rejection medications, including the recently FDA approved drug called Belatacept, is better than the current standard anti-rejection drug regimen at preventing rejection. Also to be determined will be whether the new combination of drugs will allow participants to wean off their oral anti-rejection medications over time. This study will test the safety and effectiveness of a new investigational drug combination using alemtuzumab, belatacept, and sirolimus when given with or without donor bone marrow. This combination of medicines has not been tested before in humans. Alemtuzumab (Campath) is approved for use in some types of white blood cell cancers, but is considered investigational in transplant patients. Belatacept is now FDA approved and is being studied in transplant patients. Sirolimus (Rapamune) is approved for use in transplant patients, but its use with belatacept and alemtuzumab is investigational. In the initial 20 subjects enrolled in the study, half tested whether an infusion of bone marrow from the kidney donor would improve the effect of these drugs. This bone marrow infusion was also considered investigational. Enrollment of 20 additional subjects began in January, 2013. The donor bone marrow infusion has been eliminated. Enrollment was open to primary living and deceased donor kidney recipients. Enrollment was closed as of 8/12/2014.
New Combination	NCT00565773 ↗	Belatacept Post Depletional Repopulation to Facilitate Tolerance	Completed	Emory University	Phase 2	2007-12-01	Acute rejection is a common problem after a kidney transplant. Rejection can occur when the kidney recipient's immune system tries to attack (or reject) the new kidney. Rejection typically most often develops in the first few months after a transplant. This single center study will seek to determine if a new combination of anti-rejection medications, including the recently FDA approved drug called Belatacept, is better than the current standard anti-rejection drug regimen at preventing rejection. Also to be determined will be whether the new combination of drugs will allow participants to wean off their oral anti-rejection medications over time. This study will test the safety and effectiveness of a new investigational drug combination using alemtuzumab, belatacept, and sirolimus when given with or without donor bone marrow. This combination of medicines has not been tested before in humans. Alemtuzumab (Campath) is approved for use in some types of white blood cell cancers, but is considered investigational in transplant patients. Belatacept is now FDA approved and is being studied in transplant patients. Sirolimus (Rapamune) is approved for use in transplant patients, but its use with belatacept and alemtuzumab is investigational. In the initial 20 subjects enrolled in the study, half tested whether an infusion of bone marrow from the kidney donor would improve the effect of these drugs. This bone marrow infusion was also considered investigational. Enrollment of 20 additional subjects began in January, 2013. The donor bone marrow infusion has been eliminated. Enrollment was open to primary living and deceased donor kidney recipients. Enrollment was closed as of 8/12/2014.

All Clinical Trials for Sirolimus

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00001984 ↗	Effectiveness of the Investigational Drug Campath-1H in Preventing Rejection of Transplanted Kidneys	Completed	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Phase 2	1999-11-01	This protocol will test a humanized monoclonal antibody known as Campath-1H for its ability to induce a state of permanent allograft acceptance, or tolerance, when administered in combination with a brief course of the immunosuppressive drug deoxyspergualin (DSG) at the time of human renal allotransplantation. Campath-1H is specific for the common lymphocyte and monocyte antigen CD52. Its administration temporarily depletes mature lymphocytes and some monocytes without altering neutrophils or hematopoietic stem cells. Deoxyspergualin inhibits the NFkB pathway thus preventing monocyte and macrophage activation. Recipients of living or cadaveric donor kidneys will be treated with one dose of Campath-1H prior to transplantation to insure that peripheral depletion is achieved at the time of graft reperfusion. Three subsequent doses of Campath-1H will be administered on the first, third and fifth days after the transplant to deplete passenger donor leukocytes and residual recipient cells that mobilize in response to the allograft. In addition, patients will be treated with DSG for 14 days beginning on the day prior to surgery. This trial expands on pilot studies at the NIH of 15 patients in which Campath was given alone at the time of transplantation. In those studies, excellent peripheral depletion occurred after just one dose of Campath though central depletion required additional dosing. This allowed for greatly reduced immunosuppression to be used to prevent rejection, but to date, all patients have required some immunosuppressive medication. It is hoped that the addition of DSG will eliminate the need for long-term immunosuppression. Patients will be followed closely in the post transplant period. If patients experience rejection, they will be treated with methylprednisolone and have immunosuppression added using sirolimus as the predominant immunosuppressive agent. In the previous phase of this study without DSG, this maneuver has in all cases been successful in returning the allograft to normal function. In addition to evaluating graft function following transplantation, this protocol will also characterize and evaluate the function of the immune system and the composition of the T cell repertoire following the administration of Campath-1H and DSG, and during immune system recovery after transplantation.
NCT00002790 ↗	Prevention of Graft-Versus-Host Disease in Patients With Hematologic Malignancies Who Are Receiving a Bone Marrow Transplant	Withdrawn	National Cancer Institute (NCI)	Phase 1/Phase 2	1996-03-01	RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill tumor cells. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Treatment with sirolimus, methotrexate, and cyclosporine may prevent this from happening. PURPOSE: Phase I/II trial to study the effectiveness of sirolimus plus methotrexate and cyclosporine in preventing graft-versus-host disease in patients with hematologic malignancies who are receiving a bone marrow transplant.
NCT00002790 ↗	Prevention of Graft-Versus-Host Disease in Patients With Hematologic Malignancies Who Are Receiving a Bone Marrow Transplant	Withdrawn	Fred Hutchinson Cancer Research Center	Phase 1/Phase 2	1996-03-01	RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill tumor cells. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Treatment with sirolimus, methotrexate, and cyclosporine may prevent this from happening. PURPOSE: Phase I/II trial to study the effectiveness of sirolimus plus methotrexate and cyclosporine in preventing graft-versus-host disease in patients with hematologic malignancies who are receiving a bone marrow transplant.
NCT00005113 ↗	A Study to Compare Treatment With Sirolimus Versus Standard Treatment in Patients Who Have Received a Kidney Transplant	Terminated	Boston Children's Hospital	Phase 3	1999-07-01	The purpose of this study is to compare treatment with the new drug sirolimus (SRL) versus the standard treatment with cyclosporine (CsA) or tacrolimus in children who have received kidney transplants. SRL is a new medication that may prevent the body's immune system from rejecting organ transplants. After receiving a kidney transplant, the body recognizes the donated kidney as a foreign invader and triggers the immune system to attack the kidney. This can lead to rejection of the new kidney and a failed transplant. To help reduce the risk of kidney rejection, transplant patients are given immunosuppressant drugs, which reduce the body's normal immune response and allow the transplanted organ to function. CsA or tacrolimus are two drugs that are often given to transplant patients. However, these are powerful drugs, and it can cause serious side effects and put a patient at increased risk for infections. SRL is a new drug that has been shown to reduce a transplant patient's chance of rejecting a new kidney, without serious side effects. This study is necessary to test the safety and effectiveness of SRL in children.

Clinical Trial Conditions for Sirolimus

Condition Name

Condition Name for Sirolimus
Intervention	Trials
Kidney Transplantation	49
Leukemia	23
Myelodysplastic Syndromes	21
Lymphoma	20

Condition MeSH

Condition MeSH for Sirolimus
Intervention	Trials
Graft vs Host Disease	61
Leukemia	60
Neoplasms	50
Syndrome	43

Clinical Trial Locations for Sirolimus

Trials by Country

Trials by Country for Sirolimus
Location	Trials
Canada	54
Italy	39
Spain	36
China	35
Germany	33

Trials by US State

Trials by US State for Sirolimus
Location	Trials
California	93
Maryland	89
Massachusetts	68
Florida	67
Pennsylvania	64

Clinical Trial Progress for Sirolimus

Clinical Trial Phase

Clinical Trial Phase for Sirolimus
Clinical Trial Phase	Trials
Phase 4	119
Phase 3	62
Phase 2/Phase 3	23

Clinical Trial Status

Clinical Trial Status for Sirolimus
Clinical Trial Phase	Trials
Completed	332
Recruiting	124
Terminated	61

Clinical Trial Sponsors for Sirolimus

Sponsor Name

Sponsor Name for Sirolimus
Sponsor	Trials
National Cancer Institute (NCI)	93
Wyeth is now a wholly owned subsidiary of Pfizer	46
National Institute of Allergy and Infectious Diseases (NIAID)	27

Sponsor Type

Sponsor Type for Sirolimus
Sponsor	Trials
Other	778
Industry	254
NIH	186

Sirolimus: Clinical Trials, Market Analysis, and Projections

Introduction to Sirolimus

Sirolimus, also known as rapamycin, is a potent immunosuppressant drug that inhibits the mTOR (mechanistic target of rapamycin) pathway. Initially approved by the FDA in 1999 for preventing organ rejection in kidney transplant patients, sirolimus has been explored for various other medical applications.

Clinical Trials Update

Castleman Disease Trial

A significant clinical trial involving sirolimus was conducted for patients with idiopathic (HHV-8-negative) multicentric Castleman disease (iMCD). This trial, now closed, was a collaborative effort between the Castleman Disease Collaborative Network (CDCN), the University of Pennsylvania, and the University of Arkansas for Medical Sciences. The trial aimed to evaluate sirolimus as a treatment for adults who did not benefit from anti-IL-6 therapies such as siltuximab (Sylvant) and tocilizumab (Actemra)[1].

• Enrollment Criteria: Patients had to be diagnosed with iMCD, be between 18 and 80 years old, and have active disease symptoms despite previous treatment with siltuximab or tocilizumab.
• Outcomes: Although the trial is closed, initial studies suggested that sirolimus could induce remission in patients with iMCD who did not respond to other treatments.

Vascular Anomaly Trial

The Vascular Anomaly-Sirolimus-Europe (VASE) trial is a multicentric phase III trial evaluating the efficacy and safety of sirolimus in pediatric and adult patients with symptomatic slow-flow vascular malformations. This trial, initiated in 2016, has shown promising results:

• Efficacy: Sirolimus resulted in clinical improvement in 85% of patients, with efficacy appearing within the first month for most patients[4].
• Safety: Grade 3-4 adverse events were observed in 18% of patients but resolved after treatment interruption. The treatment also increased the feasibility of surgery or sclerotherapy in 15% of patients initially deemed unsuitable.

Market Analysis

Current Market Size and Growth

The global sirolimus market has been growing steadily, driven by several key factors:

• Market Value: As of 2023, the global sirolimus market was valued at approximately USD 250-280 million[5][2].
• Growth Rate: The market is expected to grow at a compound annual growth rate (CAGR) of 4-5.8% from 2024 to 2030/2033, depending on the forecast period[3][5].

Drivers of Market Growth

Several factors are driving the growth of the sirolimus market:

• Increasing Organ Transplantations: The rise in organ transplant procedures globally has significantly increased the demand for sirolimus as an immunosuppressant to prevent rejection in transplant recipients[2][3][5].
• Expanding Applications in Oncology: Sirolimus is being explored for its potential in personalized medicine, particularly in treating cancers and other diseases where mTOR inhibition is beneficial[2].
• Emerging Markets: Targeting regions with unmet medical needs and increasing organ transplantation rates offers strategic growth opportunities[2].

Restraints and Challenges

Despite the growth potential, the sirolimus market faces some challenges:

• Adverse Effects and Safety Concerns: Sirolimus can cause significant adverse effects, which may hamper market growth. However, most adverse events are manageable with proper medical supervision[3][4].

Market Segmentation and Regional Analysis

Segmentation

The sirolimus market is segmented based on application, dosage, and distribution channels:

• Application: The market includes segments such as organ transplantation, oncology, autoimmune diseases, and vascular malformations.
• Dosage: The 0.5mg strength dominates the market due to its rising demand[2].
• Distribution Channels: The market is analyzed across various distribution channels, including hospitals, pharmacies, and online platforms[5].

Regional Analysis

The market is analyzed across several regions, including:

• North America: A significant market due to high organ transplantation rates and advanced healthcare infrastructure.
• Europe: Also a major market, driven by the high demand for immunosuppressant drugs.
• Asia Pacific: Emerging as a growth region due to increasing organ transplantation rates and improving healthcare facilities[5].

Projections and Future Outlook

Market Size Projections

By 2030/2033, the global sirolimus market is projected to reach USD 370-424 million, driven by the increasing demand for organ transplants and expanding applications in oncology and other diseases[2][3][5].

Emerging Opportunities

• Personalized Medicine: Tailoring sirolimus treatments based on patients' genetic makeup and disease characteristics offers significant opportunities for growth.
• Untapped Regions: Expanding into emerging markets with unmet medical needs provides additional growth avenues[2].

Key Takeaways

• Clinical Trials: Sirolimus has shown promising results in clinical trials for Castleman disease and vascular malformations.
• Market Growth: The global sirolimus market is growing at a CAGR of 4-5.8%, driven by increasing organ transplantations and expanding applications.
• Challenges: Adverse effects and safety concerns are key challenges, but manageable with proper medical supervision.
• Future Outlook: The market is expected to reach USD 370-424 million by 2030/2033, with opportunities in personalized medicine and emerging markets.

FAQs

What is sirolimus used for?

Sirolimus is primarily used as an immunosuppressant to prevent organ rejection in transplant patients. It is also being explored for treating various diseases, including Castleman disease, vascular malformations, and certain cancers.

What are the key drivers of the sirolimus market?

The key drivers include the increasing number of organ transplantations, expanding applications in oncology, and growth opportunities in emerging markets.

What are the potential side effects of sirolimus?

Sirolimus can cause significant adverse effects, including grade 3-4 events, but these are generally manageable with proper medical supervision.

Is sirolimus effective in treating Castleman disease?

Initial studies suggest that sirolimus can induce remission in patients with idiopathic multicentric Castleman disease who do not respond to other treatments.

What is the projected market size of sirolimus by 2030/2033?

The global sirolimus market is projected to reach USD 370-424 million by 2030/2033.

Sources

1. CDCN: Sirolimus Clinical Trial - CDCN
2. Data Bridge Market Research: Sirolimus Market Size, Growth Potential, Scope & Statistics By 2031
3. Grand View Research: Sirolimus Market Size, Share, Growth & Trends Report, 2030
4. PubMed: Preliminary results of the European multicentric phase III trial ...
5. The Brainy Insights: Sirolimus Market Analysis Report 2024