Afinitor (everolimus) has been approved by the FDA for renal angiomyolipomas (non-cancerous kidney tumors) that do not require urgent surgery in patients with TSC (tuberous sclerosis complex). Tuberous sclerosis complex is a very rare genetic condition in which non-cancerous tumors grow in the brain, kidney, skin, heart and other vital organs.

It is estimated that about 40,000 people in the USA are affected by TSC. Between 70% and 80% of those with TSC go on to develop kidney problems. Typically, a patient with TSC develops several tumors in both kidneys. As the tumors grow, they compress the kidneys, leading to bleeding and kidney failure.

mTOR kinase, a protein, plays a major role in the growth and development of several non-cancerous tumors linked to TSC. Afinitor, a pill to be taken once a day, blocks the uncontrolled activity of the protein.

In 2009, Afinitor was granted orphan drug designation for the treatment of non-cancerous kidney tumors, as well as subependymal giant cell astrocytoma (SEGA). SEGA is a type of brain tumor.

Orphan designation refers to drugs aimed at treating conditions or diseases which affect no more than 200,000 individuals in the USA, and for which the medication, based on current evidence, shows promise in the treatment of that condition or disease.

Afinitor’s lastest submission for approval was granted priority review. This is an accelerated system for reviewing drugs. In this case, the review was completed within four months.

Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said:

“This approval underscores the FDA’s commitment to the development of drugs for rare diseases with significant unmet medical needs. It also represents another example of where an understanding of a disease’s underlying biology can lead to more selective drug development.”

When reviewing Afinitor’s application, the FDA examined data from a double-blind, placebo-controlled human study involving 118 patients. Two-thirds of them were randomly selected to be administered Afinitor, while the rest were given a placebo. They were treated for up to 48 months. However, those on placebo were given the option of switching to Afinitor if their tumor grew during the study period.

All of them had tumors in both their kidneys. 40% of the participants had been treated for bleeding from the tumors. The aim of the study was to determine how many patients experienced either tumor shrinkage or the total disappearance of tumors after treatment.

42% of those on Afinitor experienced considerable reduction in tumor size – this reduction lasted for at least five months after treatment stopped. This figure included half of all patients who were on Afinitor for less than eight months. Not one patient on placebo experienced tumor shrinkage.

The FDA says it accelerated the approval process for this drug because early trial results demonstrated a very high rate of tumor reduction that lasted for several months.

Novartis, the makers and marketers of Afinitor, will have to continue monitoring patients, post-approval, for at least four years to find out how long these positive outcomes last, and how responses affect surgery requirements.

Side effects linked to Afinitor therapy included upper respiratory infection, swelling of the limbs, joint pains, abdominal pain, diarrhea, headache, couch, vomiting, nausea, sore mouth, inflamed mouth, and acne or eczema. 15% of the women on Afinitor missed at least one menstrual period during the trial.

John Bissler, MD, Clark D. West Endowed Chair of Nephrology at Cincinnati Children’s Hospital Medical Center, said:

“Renal angiomyolipomas are one of the greatest causes of morbidity and mortality in adult TSC patients and can be one of the most challenging aspects of the disease to treat. Today marks an important step for the TSC community, as Afinitor is now the only approved medicine to reduce the kidney tumor burden in these patients.”

Hervé Hoppenot, President, Novartis Oncology, said:

“With this FDA approval, Afinitor becomes the first medical option to treat two of the most debilitating manifestations of this challenging, lifelong disease – kidney tumors called renal angiomyolipomas and brain tumors known as SEGAs. This approval further strengthens our commitment to address unmet needs in TSC as we continue to research everolimus and mTOR inhibition across other manifestations of the disease.”

Written by Christian Nordvist