Sirolimus

Generic Name
Sirolimus
Brand Names
Fyarro, Hyftor, Rapamune
Drug Type
Small Molecule
Chemical Formula
C51H79NO13
CAS Number
53123-88-9
Unique Ingredient Identifier
W36ZG6FT64
Background

Sirolimus, also known as rapamycin, is a macrocyclic lactone antibiotic produced by bacteria Streptomyces hygroscopicus, which was isolated from the soil of the Vai Atari region of Rapa Nui (Easter Island). It was first isolated and identified as an antifungal agent with potent anticandida activity; however, after its potent antitumor and immunosuppressive activities were later discovered, it was extensively investigated as an immunosuppressive and antitumour agent. Its primary mechanism of action is the inhibition of the mammalian target of rapamycin (mTOR), which is a serine/threonine-specific protein kinase that regulates cell growth, proliferation, and survival. mTOR is an important therapeutic target for various diseases, as it was shown to regulate longevity and maintain normal glucose homeostasis. Targeting mTOR received more attention especially in cancer, as mTOR signalling pathways are constitutively activated in many types of human cancer.

Sirolimus was first approved by the FDA in 1999 for the prophylaxis of organ rejection in patients aged 13 years and older receiving renal transplants. In November 2000, the drug was recognized by the European Agency as an alternative to calcineurin antagonists for maintenance therapy with corticosteroids. In May 2015, the FDA approved sirolimus for the treatment of patients with lymphangioleiomyomatosis. In November 2021, albumin-bound sirolimus for intravenous injection was approved by the FDA for the treatment of adults with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumour (PEComa). Sirolimus was also investigated in other cancers such as skin cancer, Kaposi’s Sarcoma, cutaneous T-cell lymphomas, and tuberous sclerosis. The topical formulation of sirolimus, marketed as HYFTOR, was approved by the FDA in April 2022: this marks the first topical treatment approved in the US for facial angiofibroma associated with tuberous sclerosis complex.

Indication

Sirolimus is indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving renal transplants. In patients at low-to moderate-immunologic risk, it is recommended that sirolimus be used initially in a regimen with cyclosporine and corticosteroids; cyclosporine should be withdrawn two to four months after transplantation. In patients at high-immunologic risk (defined as Black recipients and/or repeat renal transplant recipients who lost a previous allograft for immunologic reason and/or patients with high panel-reactive antibodies [PRA; peak PRA level > 80%]), it is recommended that sirolimus be used in combination with cyclosporine and corticosteroids for the first year following transplantation.

It is also used to treat lymphangioleiomyomatosis.

In the US, albumin-bound sirolimus for intravenous injection is indicated for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumour (PEComa).

In Europe, it is recommended that sirolimus for the prophylaxis of organ rejection in renal transplants is used in combination with cyclosporin microemulsion and corticosteroids for two to three months. Sirolimus may be continued as maintenance therapy with corticosteroids only if cyclosporin microemulsion can be progressively discontinued.

Topical sirolimus is indicated for the treatment of facial angiofibroma associated with tuberous sclerosis in adults and pediatric patients six years of age and older.

Associated Conditions
Chordomas, Facial Angiofibroma, Graft-versus-host Disease (GVHD), Heart Transplant Rejection, Liver Transplant Rejection, Lung Transplant Rejection, Lymphangioleiomyomatosis (LAM), Renal Angiomyolipomas, Transplanted Organ Rejection, Metastatic malignant Perivascular Epithelioid Cell Neoplasms, Unresectable, locally advanced malignant Perivascular Epithelioid Cell Neoplasms
Associated Therapies
-

Rapamycin Treatment for ALS

First Posted Date
2017-12-02
Last Posted Date
2022-08-11
Lead Sponsor
Azienda Ospedaliero-Universitaria di Modena
Target Recruit Count
63
Registration Number
NCT03359538
Locations
🇮🇹

Centro Clinico Nemo, Fondazione Serena Onlus, Milano, Milano, Italy

🇮🇹

Centro Sla, Irccs A.O.U. S.Martino Ist, Genova, Genova, Italy

🇮🇹

Centro Sla, Irccs Istituto Carlo Besta, Milano, Milano, Italy

and more 4 locations

Secondary Prevention Trial of Rapamycin in Patients With Resected Non-muscle Invasive Bladder Cancer

Phase 3
Withdrawn
Conditions
Interventions
First Posted Date
2017-10-02
Last Posted Date
2019-06-12
Lead Sponsor
The University of Texas Health Science Center at San Antonio
Registration Number
NCT03298958
Locations
🇺🇸

University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

The Effect and Safety Profile of Thymoglobulin® in Primary Cardiac Transplant Recipients

First Posted Date
2017-09-26
Last Posted Date
2024-12-16
Lead Sponsor
Cedars-Sinai Medical Center
Target Recruit Count
60
Registration Number
NCT03292861
Locations
🇺🇸

Cedars-Sinai Medical Center, Los Angeles, California, United States

🇺🇸

Kaiser Permanente Los Angeles Medical Center, Los Angeles, California, United States

Resveratrol and Sirolimus in Lymphangioleiomyomatosis Trial

Phase 2
Completed
Conditions
Interventions
First Posted Date
2017-08-18
Last Posted Date
2023-02-01
Lead Sponsor
University of Cincinnati
Target Recruit Count
25
Registration Number
NCT03253913
Locations
🇺🇸

University of Cincinnati, Cincinnati, Ohio, United States

Efficacy of Rapamycin in the Treatment of Cervico-facial Lymphatic Malformations

First Posted Date
2017-08-08
Last Posted Date
2022-08-17
Lead Sponsor
University Hospital, Lille
Target Recruit Count
28
Registration Number
NCT03243019
Locations
🇫🇷

Hôpital Jeanne de Flandres, CHU, Lille, France

🇫🇷

Hu Robert Debre Aphp - Paris, Paris, France

Ixazomib in the Prophylaxis of Chronic Graft-versus-host Disease.

First Posted Date
2017-07-21
Last Posted Date
2024-03-20
Lead Sponsor
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Target Recruit Count
142
Registration Number
NCT03225417
Locations
🇪🇸

Hospital Universitario Vall D´Hebrón, Barcelona, Spain

🇪🇸

Hospital Clinic de Barcelona, Barcelona, Spain

🇪🇸

ICO- Hospital Germans Trias i Pujol, Badalona, Spain

and more 5 locations

Epacadostat (INCB24360) in Combination With Sirolimus in Advanced Malignancy

First Posted Date
2017-07-14
Last Posted Date
2023-05-03
Lead Sponsor
Chao Huang
Target Recruit Count
15
Registration Number
NCT03217669
Locations
🇺🇸

Clinical Research Center, Fairway, Kansas, United States

🇺🇸

The University of Kansas Cancer Center, Westwood, Kansas, United States

Nonmyeloablative Stem Cell Transplant in Children with Sickle Cell Disease and a Major ABO-Incompatible Matched Sibling Donor

First Posted Date
2017-07-11
Last Posted Date
2024-12-10
Lead Sponsor
University of Calgary
Target Recruit Count
12
Registration Number
NCT03214354
Locations
🇨🇦

Alberta Children's Hospital, Calgary, Alberta, Canada

© Copyright 2024. All Rights Reserved by MedPath