Everolimus has become the first drug approved for the treatment of noncancerous renal angiomyolipomas that do not require immediate surgery in patients with tuberous sclerosis complex, the Food and Drug Administration announced April 26.
The new indication is based on a double-blind, randomized, placebo-controlled study of 118 patients with tuberous sclerosis complex and bilateral kidney tumors. The angiomyolipoma response rate among those treated with everolimus (Afinitor) was 42%, compared with zero among those on placebo, according to the FDA statement and revised drug label. The median duration of the response was at least 5.3 months.
Along with common side effects including 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, the FDA noted that about 15% of female patients receiving everolimus missed one or more menstrual periods during the study.
Everolimus is a mammalian target of rapamycin (mTOR) inhibitor. Taken orally once a day, it blocks a protein that "plays a critical role in the development and growth of the various noncancerous tumors occurring in patients with tuberous sclerosis complex, a rare genetic disorder, the statement said.
An estimated 40,000 people in the United States have tuberous sclerosis complex, a genetic condition that causes multiple noncancerous tumors in the brain, kidney, and other vital organs; about 70%-80% develop kidney problems, according to the FDA.
First approved in 2009, everolimus is marketed by Novartis. It was previously approved for subependymal giant cell astrocytoma associated with tuberous sclerosis complex in adults and children who require therapeutic intervention but are not candidates for curative surgical resection.
It is also approved for treatment of adults with progressive neuroendocrine tumors of pancreatic origin that is unresectable, locally advanced, or metastatic, and for adults with advanced renal cell carcinoma after treatment with sunitinib (Sutent) or sorafenib (Nexavar) has failed.
The new indication is an accelerated approval, which requires Novartis to follow patients for at least 4 years "to determine the duration of these responses and how responses affect the need for surgery and the control of the disease."