The FDA approved Afinitor (everloimus), the first drug approved specifically to treat non-cancerous kidney tumors (renal angiomyolipomas) not requiring immediate surgery in patients with tuberous sclerosis complex (TSC).
TSC is a rare genetic disease that causes the growth of various non-cancerous tumors in the brain, kidney and other vital organs. TSC generally causes multiple tumors in both kidneys that compress normal kidney tissues as they increase in size, leading to kidney failure and bleeding.
Afinitor is a pill taken once daily and blocks the uncontrolled activity of mTOR kinase, a certain protein which plays a critical role in the development and growth of the various non-cancerous tumors occurring in patients with TSC.
Afinitor was granted orphan drug designations to treat renal angiomyolipomas and a certain type of brain tumor called subependymal giant cell astrocytoma (SEGA) in patients with TSC in 2009. An orphan designation is given to a drug intended to treat a disease or condition affecting fewer than 200,000 patients in the United States and for which the drug, based on supporting data, has shown promise in the treatment of the disease.
The drug’s application was granted priority review, a designation given to drugs that offer major advancements in treatment or provide a treatment where no adequate therapy exists. FDA completed review of this application in four months.
Afinitor’s safety and efficacy were established in a double-blind, placebo-controlled clinical trial of 118 patients. Two-thirds of the patients were randomly chosen to receive Afinitor and one-third was assigned to receive a placebo. Patients were to be treated for up to four years, but patients receiving the placebo were offered Afinitor treatment if their kidney tumors grew while on study.
All patients had tumors in both kidneys, and about 40% had undergone a procedure to control bleeding from the tumors. The trial was designed to measure the percentage of patients whose tumor shrank or disappeared after treatment. With half of the patients receiving less than eight months of treatment, 42 % of those treated with Afinitor showed a substantial reduction in tumor size lasting, on average, more than five months. None of those receiving placebo had tumor shrinkage.
Afinitor also was granted accelerated approval for this indication because early results showed a high rate of tumor reduction that lasted for several months. As part of this approval, Afinitor’s manufacturer must continue to follow the patients for at least four years to determine the duration of these responses and how responses affect the need for surgery and the control of the disease.
The most common side effects with Afinitor were inflamed or sore mouth, nausea or vomiting, skin problems (acne or eczema), cough, headache, diarrhea, abdominal pain, joint pains, swelling of legs or arms, and upper respiratory infection. Additionally, 15% of female patients receiving Afinitor had one or more missed menstrual periods during the study.
The FDA has previously approved Afinitor to treat patients with advanced renal cell carcinoma that has progressed after treatment with other cancer therapies; SEGA associated with TSC in patients who require treatment but are not candidates for surgical removal of the tumor; and progressive neuroendocrine tumors located in the pancreas that cannot be removed by surgery or that have spread to other parts of the body.
Afinitor is marketed by East Hanover, N.J.-based Novartis.