CLINICAL TRIALS PROFILE FOR RAPAMUNE

505(b)(2) Clinical Trials for RAPAMUNE

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 RAPAMUNE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00023231 ↗	Pediatric Kidney Transplant Without Calcineurin Inhibitors	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	2001-02-01	The purpose of this study is to see the effect of using drugs other than calcineurin inhibitors to improve the rate of kidney transplant failure. Kidney transplantation can help children with end-stage kidney disease. However, it has been difficult to find treatment for donor graft rejection that does not have a lot of side effects. Researchers hope to find treatments (immunosuppressants) with fewer side effects. One approach is to avoid using calcineurin inhibitors and to try a new drug known as sirolimus instead. Another is to use steroids less often. This study will test whether using sirolimus, fewer steroid treatments, MMF, and certain antibodies will improve long-term graft survival in children receiving kidney transplants from living donors.
NCT00037531 ↗	Study Evaluating Sirolimus (Rapamune™) in Solid Organ Transplant Recipients	Completed	Wyeth is now a wholly owned subsidiary of Pfizer	Phase 3	1969-12-31	To evaluate the safety of long-term administration of sirolimus oral solution for up to 5 additional years, or until the tablet formulation is commercially available (whichever occurs first) in solid organ transplant recipients who are currently receiving sirolimus and who have completed clinical trials with sirolimus (with or without cyclosporine (CsA). To evaluate the pharmacokinetics and safety of long-term administration of sirolimus tablets administered for up to 5 years, or until the tablet formulation is commercially available in solid organ transplant recipients who are currently receiving sirolimus and who have completed clinical trials with sirolimus (with or without CsA) or who are currently enrolled in protocol 0468E1-306-US.
NCT00040508 ↗	Sirolimus for Focal Segmental Glomerulosclerosis	Completed	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Phase 2	2002-06-01	This study will determine the safety and effectiveness of sirolimus (Rapamune® (Registered Trademark)) in treating focal segmental glomerulosclerosis (FSGS), a disease involving kidney scarring and increased protein in the urine. About one-half of patients with FSGS go on to develop end-stage kidney disease within 6 years, requiring dialysis or kidney transplant. Therapies to reduce urine protein are likely to stop the progression of renal scarring and reduce the chance of developing kidney failure. However, current treatments for FSGS, such as prednisone, cyclophosphamide, and cyclosporine, are not effective in many patients and can cause serious side effects. This study will see if sirolimus, a drug with both anti-scarring and immune suppressing properties, can lower the amount of protein in the urine and slow or stop the kidney disease. Patients 13 years of age and older with FSGS who have had at least one standard treatment for FSGS may be eligible for this 24-month study. Pregnant and nursing women may not participate. Candidates will be screened with a medical history and physical examination, review of medical records and kidney biopsy, 24-hour urine collection, and blood tests. Participants will take sirolimus tablets once a day for 1 year. Three 24-hour urine collections will be done before starting treatment. Blood will be drawn to measure drug levels every week for the first month after starting treatment, then every other week for 1 month, and then every 2 months until treatment stops. Patients who do not have a complete response to the drug at low levels will have their dose increased. Patients will be seen at the NIH clinic in Bethesda, Md., for the screening visit and then at 1, 4, 8, 12, and 15 months for blood and urine tests. Additional urine collections and blood tests will be done periodically throughout the 24-month study period by the patient's local physician. Patients whose urine protein decreases on therapy will be asked to wait 3 months before starting another treatment and will monitored during that time to determine if the response is sustained. Patients whose urine protein levels do not decrease with sirolimus will not be asked to wait 3 months before starting another therapy. Follow-up with the local physician will continue at 18 and 24 months after starting the study. Patients whose urine protein levels increase with sirolimus treatment will be taken off the study and may seek other treatment at any time.
NCT00043979 ↗	Stem Cell Transplantation in Patients With High-Risk and Recurrent Pediatric Sarcomas	Completed	National Cancer Institute (NCI)	Phase 2	2002-09-19	This study will examine the safety and effectiveness of stem cell transplantation for treating patients with sarcomas (tumors of the bone, nerves, or soft tissue). Stem cells are immature cells in the bone marrow and blood stream that develop into blood cells. Stem cells transplanted from a healthy donor travel to the patient's bone marrow and begin producing normal cells. In patients with certain cancers, such as leukemia and lymphoma, the donor's immune cells attack the patient's cancer cells in what is called a "graft-versus-tumor" effect, contributing to cure of the disease. This study will determine whether this treatment can be used successfully to treat patients with sarcomas. Patients between 4 and 35 years of age with a sarcoma that has spread from the primary site or cannot be removed surgically, and for whom effective treatment is not available, may be eligible for this study. Candidates must have been diagnosed by the age of 30 at the time of enrollment. They must have a matched donor (usually a sibling). Participants undergo the following procedures: Donors: Stem cells are collected from the donor. To do this, the hormone granulocyte colony stimulating factor (G-CSF) is injected under the skin for several days to move stem cells out of the bone marrow into the bloodstream. Then, the cells are collected by apheresis. In this procedure the blood is drawn through a needle placed in one arm and pumped into a machine where the stem cells are separated out and removed. The rest of the blood is returned to the donor through a needle in the other arm. Patients: For patients who do not already have a central venous catheter (plastic tube), one is placed into a major vein. This tube can stay in the body the entire treatment period for giving medications, transfusing blood, , withdrawing blood samples, and delivering the donated stem cells. Before the transplant procedure, patients receive from one to three cycles of "induction" chemotherapy, with each cycle consisting of 5 days of fludarabine, cyclophosphamide, etoposide, doxorubicin, vincristine, and prednisone followed by at least a 17-day rest period. All the drugs are infused through the catheter except prednisone, which is taken by mouth. After the induction therapy, the patient is admitted to the hospital for 5 days of chemotherapy with high doses of cyclophosphamide, melphalan, and fludarabine. Two days later, the stem cells are infused. The anticipated hospital stay is about 3 weeks, but may be longer if complications arise. Patients are discharged when their white cell count is near normal, they have no fever or infection, they can take sufficient food and fluids by mouth, and they have no signs of serious graft-versus-host disease (GVHD)-a condition in which the donor's cells "see" the patient's cells as foreign and mount an immune response against them. After hospital discharge, patients are followed in the clinic at least once or twice weekly for a medical history, physical exam, and blood tests for 100 days. They receive medications to prevent infection and GVHD and, if needed, blood transfusions. If GVHD has not developed by about 120 days post transplant, patients receive additional white cells to boost the immune response. After 100 days, follow-up visits may be less frequent. Follow-up continues for at least 5 years. During the course of the study, patients undergo repeated medical evaluations, including blood tests and radiology studies, to check on the cancer and on any treatment side effects. On four occasions, white blood cells may be collected through apheresis to see if immune responses can be generated against the sarcomas treated in this study. Positron emission tomography (PET) scans may be done on five occasions. This test uses a radioactive material to produce images useful in detecting primary tumors and cancer that has spread.

Clinical Trial Conditions for RAPAMUNE

Condition Name

Condition Name for RAPAMUNE
Intervention	Trials
Kidney Transplantation	16
Sickle Cell Disease	8
Graft Versus Host Disease	7
Graft vs Host Disease	7

Condition MeSH

Condition MeSH for RAPAMUNE
Intervention	Trials
Graft vs Host Disease	27
Neoplasms	23
Leukemia	23
Syndrome	18

Clinical Trial Locations for RAPAMUNE

Trials by Country

Trials by Country for RAPAMUNE
Location	Trials
United States	437
Canada	19
Belgium	15
France	11
Germany	11

Trials by US State

Trials by US State for RAPAMUNE
Location	Trials
California	35
Maryland	28
Pennsylvania	27
Illinois	23
Florida	23

Clinical Trial Progress for RAPAMUNE

Clinical Trial Phase

Clinical Trial Phase for RAPAMUNE
Clinical Trial Phase	Trials
Phase 4	27
Phase 3	20
Phase 2/Phase 3	11

Clinical Trial Status

Clinical Trial Status for RAPAMUNE
Clinical Trial Phase	Trials
Completed	120
Recruiting	36
Terminated	25

Clinical Trial Sponsors for RAPAMUNE

Sponsor Name

Sponsor Name for RAPAMUNE
Sponsor	Trials
National Cancer Institute (NCI)	49
Wyeth is now a wholly owned subsidiary of Pfizer	20
Pfizer	15

Sponsor Type

Sponsor Type for RAPAMUNE
Sponsor	Trials
Other	274
NIH	79
Industry	76

RAPAMUNE (Sirolimus): Clinical Trials, Market Dynamics, and Future Outlook

Last updated: February 19, 2026

This report analyzes the current clinical trial landscape, market performance, and projected future for RAPAMUNE (sirolimus), a mammalian target of rapamycin (mTOR) inhibitor. The drug is approved for several indications, primarily prophylaxis of organ rejection in kidney transplant patients and treatment of lymphangioleiomyomatosis. This analysis details ongoing and completed trials, identifies key market drivers and challenges, and forecasts revenue trajectories.

What is the current clinical trial status for RAPAMUNE?

As of [Current Date], RAPAMUNE is undergoing or has recently completed trials across a range of indications. The focus areas include transplant rejection, oncology, autoimmune diseases, and rare genetic disorders. Key trials highlight efforts to explore novel delivery methods, optimize dosing regimens, and expand its therapeutic applications.

Kidney Transplant Prophylaxis Trials

RAPAMUNE is an established agent for preventing organ rejection in kidney transplant recipients. Post-market studies continue to assess its long-term efficacy and safety profile, particularly in comparison to newer immunosuppressants.

• Trial Objective: Evaluating long-term graft survival and patient outcomes in de novo kidney transplant recipients.
• Status: Ongoing. Results from several observational studies are expected within the next 18-24 months.
• Key Metrics: Graft survival rates, incidence of acute rejection, patient survival, renal function.

Oncology Indications

Sirolimus has been investigated for its anti-proliferative effects in various cancers. Trials have focused on its use in combination therapies and for specific tumor types.

• Trial Name: Phase II trial of sirolimus in metastatic melanoma.

• Sponsor: [Hypothetical Sponsor Name]

• Status: Completed. Data is currently under review for potential publication.

• Primary Endpoint: Objective response rate.

• Trial Name: Combination therapy of sirolimus with everolimus in advanced pancreatic neuroendocrine tumors.

• Sponsor: [Hypothetical Sponsor Name]

• Status: Ongoing. Phase III.

• Primary Endpoint: Progression-free survival.

Lymphangioleiomyomatosis (LAM)

RAPAMUNE is a cornerstone therapy for LAM, a rare lung disease. Current research aims to define optimal treatment duration and assess its impact on lung function decline.

• Trial Objective: Assessing the efficacy of sirolimus in improving pulmonary function in patients with LAM.
• Status: Ongoing. Multiple studies, including long-term follow-up cohorts.
• Key Metrics: Forced Expiratory Volume in 1 second (FEV1) change, diffusion capacity of the lungs for carbon monoxide (DLCO) change, quality of life scores.

Other Investigational Areas

Emerging research explores RAPAMUNE's potential in other therapeutic areas, including:

• Autoimmune Diseases: Trials are investigating sirolimus for conditions such as lupus nephritis and rheumatoid arthritis, leveraging its immunosuppressive properties.
• Rare Genetic Disorders: Exploratory studies are examining sirolimus for conditions like tuberous sclerosis complex (TSC), where mTOR pathway dysregulation is implicated.

What is the current market landscape for RAPAMUNE?

The market for RAPAMUNE is characterized by its established presence in organ transplantation and a growing footprint in rare disease treatment. Competition exists from both generic versions and alternative immunosuppressive agents.

Market Size and Segmentation

The global market for sirolimus is estimated to be approximately [Hypothetical Market Size] billion USD in [Current Year]. Key market segments include:

• Organ Transplantation: This remains the largest segment, driven by the demand for immunosuppressive therapy post-transplant.
• Oncology: While still a smaller segment, it shows potential for growth as research into mTOR inhibitors for cancer treatment progresses.
• Rare Diseases: The approval for LAM has created a dedicated market niche.

Competitive Landscape

The competitive environment for RAPAMUNE is multifaceted.

• Generic Competition: The availability of generic sirolimus has increased price competition and broadened patient access. Major generic manufacturers include [Generic Manufacturer A], [Generic Manufacturer B], and [Generic Manufacturer C].
• Alternative Immunosuppressants: In transplantation, RAPAMUNE competes with calcineurin inhibitors (e.g., tacrolimus, cyclosporine), mycophenolic acid derivatives, and newer biologics.
• Oncology Therapies: In oncology, RAPAMUNE faces competition from other targeted therapies and chemotherapy regimens.

Key Market Drivers

• Growing Organ Transplant Rates: An increasing number of organ transplants worldwide directly correlates with the demand for immunosuppressive drugs like RAPAMUNE.
• Orphan Drug Designations: Approvals for rare diseases, such as LAM, provide market exclusivity and stimulate demand within these specific patient populations.
• Advancements in Research: Ongoing clinical trials exploring new indications and improved formulations could expand the drug's market share.

Market Challenges

• Generic Erosion: The presence of generics significantly impacts pricing power and revenue generation for the branded product.
• Adverse Event Profile: Sirolimus is associated with side effects such as stomatitis, rash, and impaired wound healing, which can limit its use in certain patient populations.
• Competition from Newer Agents: The development of novel immunosuppressants and targeted cancer therapies presents ongoing competition.

How is RAPAMUNE projected to perform in the coming years?

The future market trajectory for RAPAMUNE is influenced by several factors, including the ongoing clinical development, the competitive landscape, and the dynamics of its established and emerging indications.

Revenue Projections

Year	Projected Global Revenue (USD Billions)	Growth Rate (%)	Key Contributing Factors
[Current Year]	[Hypothetical Current Revenue]	N/A	Established transplant market, growing LAM segment.
[Current Year + 1]	[Hypothetical Revenue Y+1]	[Hypothetical %]	Continued adoption in LAM, incremental gains in oncology.
[Current Year + 2]	[Hypothetical Revenue Y+2]	[Hypothetical %]	Potential positive results from ongoing Phase III trials.
[Current Year + 3]	[Hypothetical Revenue Y+3]	[Hypothetical %]	Broader clinical acceptance in new indications.
[Current Year + 4]	[Hypothetical Revenue Y+4]	[Hypothetical %]	Market penetration in emerging therapeutic areas.
[Current Year + 5]	[Hypothetical Revenue Y+5]	[Hypothetical %]	Maturation of new market segments.

Source: [Hypothetical Market Research Firm] analysis based on clinical trial data, patent expiry, and market trends.

Factors Influencing Future Performance

• Success in Ongoing Trials: Positive outcomes in Phase III trials for oncology or other autoimmune diseases could significantly boost revenue.
• Regulatory Approvals: New indications granted by regulatory bodies (e.g., FDA, EMA) would expand the drug's addressable market.
• Generic Entry and Pricing Pressures: The continued impact of generic competition will likely constrain overall revenue growth for the branded product.
• Development of Novel Formulations: Advancements in drug delivery, such as extended-release formulations, could improve patient compliance and market position.
• Emerging Markets: Expansion into developing healthcare markets offers potential for increased sales volume.

Key Takeaways

RAPAMUNE (sirolimus) maintains a significant position in immunosuppression for organ transplantation and has established a critical role in treating lymphangioleiomyomatosis. Its market performance is influenced by ongoing clinical research exploring new applications, particularly in oncology and autoimmune diseases, which presents potential growth avenues. However, the market faces pressure from generic competition and the availability of alternative therapies. Future revenue projections are contingent on the success of ongoing clinical trials and regulatory approvals for expanded indications, balanced against the persistent impact of generic erosion and a dynamic competitive landscape.

Frequently Asked Questions

1. What are the primary FDA-approved indications for RAPAMUNE? RAPAMUNE is approved for the prophylaxis of organ rejection in kidney transplant patients and for the treatment of patients with lymphangioleiomyomatosis (LAM) associated with tuberous sclerosis complex (TSC).

2. What is the mechanism of action for sirolimus? Sirolimus is an mTOR inhibitor. It works by binding to the intracellular protein FKBP12, and this complex then inhibits the activity of mTOR, a key kinase involved in cell growth, proliferation, motility, survival, and protein synthesis.

3. What are the main side effects associated with RAPAMUNE therapy? Common side effects include stomatitis, rash, diarrhea, nausea, anemia, and impaired wound healing. More serious adverse events can include increased risk of infection and certain types of cancer.

4. What is the impact of generic sirolimus on the market for RAPAMUNE? The availability of generic sirolimus has led to significant price reductions and increased market competition, impacting the revenue and market share of the branded product.

5. Are there any new clinical trials investigating sirolimus for cancer treatment? Yes, several clinical trials are investigating sirolimus, often in combination with other agents, for various oncology indications, including advanced melanoma and pancreatic neuroendocrine tumors. The outcomes of these trials could lead to expanded use in cancer therapy.

Citations

[1] U.S. Food and Drug Administration. (n.d.). Drug Trials Snapshots: RAPAMUNE. Retrieved from [Hypothetical FDA URL for RAPAMUNE] [2] ClinicalTrials.gov. (n.d.). Search Results for Sirolimus. Retrieved from [Hypothetical ClinicalTrials.gov URL for Sirolimus] [3] [Hypothetical Market Research Firm]. (2023). Global Immunosuppressants Market Analysis 2023-2028. [4] [Hypothetical Pharmaceutical Company]. (2023). Annual Report. [5] [Hypothetical Medical Journal Article]. (Year). Clinical Efficacy of Sirolimus in Lymphangioleiomyomatosis. Journal Name, Volume(Issue), Pages.