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Afinitor (everolimus)
Afinitor works by blocking the mTOR protein, which is involved in cell growth and division.
Afinitor (everolimus) is a kinase inhibitor small molecule developed by Novartis that targets the serine/threonine-protein kinase mTOR. It is used to treat various conditions, including kidney and breast cancers, as well as a rare brain tumor associated with Tuberous Sclerosis. Afinitor is off-patent and has multiple generic manufacturers. It has been FDA-approved since 2009 for several indications. As a commercial product, it is available in the market with various generic options.
At a glance
| Generic name | everolimus |
|---|---|
| Sponsor | Novartis |
| Drug class | Kinase Inhibitor [EPC] |
| Target | Serine/threonine-protein kinase mTOR |
| Therapeutic area | Oncology |
| Phase | FDA-approved |
| First approval | 2009 |
| Annual revenue | 600 |
Mechanism of action
Everolimus is an inhibitor of mammalian target of rapamycin (mTOR), serine-threonine kinase, downstream of the PI3K/AKT pathway. The mTOR pathway is dysregulated in several human cancers and in tuberous sclerosis complex (TSC). Everolimus binds to an intracellular protein, FKBP-12, resulting in an inhibitory complex formation with mTOR complex (mTORC1) and thus inhibition of mTOR kinase activity. Everolimus reduced the activity of S6 ribosomal protein kinase (S6K1) and eukaryotic initiation factor 4E-binding protein (4E-BP1), downstream effectors of mTOR, involved in protein synthesis. S6K1 is substrate of mTORC1 and phosphorylates the activation domain of the estrogen receptor which results in ligand-independent activation of the receptor. In addition, everolimus inhibited the expression of hypoxia-inducible factor (e.g., HIF-1) and reduced the expression of vascular endothelial growth factor (VEGF). Inhibition of mTOR by everolimus has been shown to reduce c
Approved indications
- Angiomyolipoma of kidney
- Carcinoma of breast
- Hormone receptor positive malignant neoplasm of breast
- Pancreatic Neuroendocrine Tumor
- Prevention of Kidney Transplant Rejection
- Renal cell carcinoma
- Subependymal Giant Cell Astrocytoma associated with Tuberous Sclerosis
- Tuberous sclerosis syndrome
Common side effects
- Stomatitis
- Infections
- Asthenia
- Fatigue
- Cough
- Diarrhea
- Nausea
- Vomiting
- Pyrexia
- Mucosal inflammation
- Dyspnea
- Pneumonitis
Drug interactions
- amobarbital
- amprenavir
- aprepitant
- aprobarbital
- atazanavir
- barbital
- boceprevir
- carbamazepine
- ciprofloxacin
- clarithromycin
- conivaptan
- darunavir
Key clinical trials
- Efficacy and Safety of RAD001 in Patients Aged 18 and Over With Angiomyolipoma Associated With Either Tuberous Sclerosis Complex (TSC) or Sporadic Lymphangioleiomyomatosis (LAM) (PHASE3)
- RAD001 Plus Best Supportive Care (BSC) Versus BSC Plus Placebo in Patients With Metastatic Carcinoma of the Kidney Which Has Progressed After Treatment With Sorafenib and/or Sunitinib (PHASE3)
- Efficacy and Safety of Everolimus (RAD001) in Patients of All Ages With Subependymal Giant Cell Astrocytoma Associated With Tuberous Sclerosis Complex (TSC)(EXIST-1) (PHASE3)
- Everolimus (RAD001) Therapy of Giant Cell Astrocytoma in Patients With Tuberous Sclerosis Complex (PHASE1,PHASE2)
- Testing Lutetium Lu 177 Dotatate in Patients With Somatostatin Receptor Positive Advanced Bronchial Neuroendocrine Tumors (PHASE2)
- Comparing Retreatment of 177Lu-DOTATATE PRRT Versus the Usual Treatment in Patients With Metastatic Unresectable Gastroenteropancreatic Neuroendocrine Tumors, NET RETREAT Trial (PHASE2)
- RAD001 in Combination With PKC412 in Patients With Relapsed, Refractory or Poor Prognosis AML or MDS (PHASE1)
- Esprit BTK Post-Approval Study (NA)
Patents
| Patent | Expiry | Type |
|---|---|---|
| 9006224 | 2028-07-01 | Method of Use |
| 8410131 | 2025-11-01 | Method of Use |
| 8410131*PED | 2026-05-01 | Compound |
Primary sources
Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.
| Source | Used for |
|---|---|
| FDA label | Mechanism, indications, dosing, boxed warnings, drug interactions |
| ClinicalTrials.gov | Trial enrolment, design, endpoints, results |
| FDA Orange Book | Patents + exclusivity |
| SEC EDGAR | Revenue + earnings |