Everolimus 159351-69-6

Recently, other applications for Everolimus have entered the world of interventional cardiology in the form of additives in coronary artery stents. Data from the SPIRIT III trial, published on January 2011, found that Everolimus-eluting stents were superior in terms of safety and efficacy compared to first-generation drug-eluting stents. Everolimus is now currently used in the popular XIENCE V® and XIENCE nano™ drug-eluting stents. Furthermore, the PLATINUM trial presented during the American College of Cardiology 2011 Scientific Sessions, using platinum as the new alloy base for the stent, added more evidence favoring the use of Everolimus in stents even when using non-chromium-cobalt based stents.

From cancer to interventional cardiology, the efficacy of Everolimus has been established. Since this drug was able to find use in two very different fields of medicine, the potential use of  Everolimus for other indications does not seem like a farfetched idea at all.

LGM Pharma prides itself in its role in supplying quality active pharmaceutical agents as well as formulations to biopharmaceuticals intended for research and development. Everolimus CAS#: 159351-69-6 is one of the many active pharmaceutical agents supplied by LGM Pharma to its clients. The company strongly believes in supply consistency, drug safety and efficacy. It supports the tireless efforts of its clients in introducing innovative medical and pharmaceutical solutions to everyday problems that plague human life. Because of this noble cause, supplying superior product quality is of utmost importance to LGM Pharma and has never compromised on this stance nor it ever will.

General Information

Everolimus (RAD-001) is the 40-O-(2-hydroxyethyl) derivative of sirolimus and works similarly to sirolimus as an mTOR inhibitor. It is currently used as an immunosuppressant to prevent rejection of organ transplants and treatment of renal cell cancer. Much research has also been conducted on everolimus and other mTOR inhibitors for use in a number of cancers. It is marketed by Novartis under the tradenames Zortress (USA) and Certican (Europe and other countries) in transplantation medicine, and Afinitor in oncology.

Approvals and indications

Everolimus is approved for various conditions:

• Advanced kidney cancer (approved in March 2009)
• Prevention of organ rejection after renal transplant(April 2010)
• Subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis (TS) in patients who are not suitable for surgical intervention (October 2010)
• Progressive or metastatic pancreatic neuroendocrine tumors not surgically removable (May 2011)

Clinical trials

Phase III trials are under way in breast cancer, gastric cancer, hepatocellular carcinoma and lymphoma. Interim phase III trial results in 2011 show that adding Afinitor (everolimus) to exemestane therapy against advanced breast cancer can significantly improve progression-free survival compared with exemestane therapy alone.

Mechanism

In a similar fashion to other mTOR inhibitors its effect is solely on the mTORC1 protein and not on the mTORC2 protein. This can lead to a hyper-activation of the kinase AKT via inhibition on the mTORC1 negative feedback loop while not inhibiting the mTORC2 positive feedback to AKT. This AKT elevation can lead to longer survival in some cell types.

Role in heart transplantation

Everolimus may have a role in heart transplantation as it has been shown to reduce chronic allograft vasculopathy in such transplants. It also may have a similar role to sirolimus in kidney and other transplants. Because hypercholesterolemia and hypertriglyceridemia have been reported, monitoring of blood lipid level is recommended.

Use in vascular stents

Everolimus is used in drug-eluting coronary stents as an immunosuppressant to prevent restenosis. Abbott Vascular produces an everolimus-eluting stent called the Xience V. It utilizes the Multi-Link Vision cobalt chromium stent platform and Novartis' everolimus. The product is also currently an investigational device in the United States and Japan. It is also available under a private-label version called the PROMUS Everolimus-Eluting Coronary Stent System and it is currently available in most major European and Asia-Pacific markets.